Libre Pathology - User contributions [en]

User talk:Michael

2015-02-17T15:11:52Z

Ana:

[[Image:Yakyakyak.gif|center]]
==Editing==
HI Michael - I was trying to form a page for mesenchymal chondrosarcoma with much failure - so I stuck what I was working on in the chondrosarc summary. If you can form a page for it great - if not I'll alter the format it's is in now. Cheers - [[User:Sarah|Sarah]] ([[User talk:Sarah|talk]]) 23:43, 19 November 2014 (EST)

Thanks Michael - I couldnt figure out how to get to a redirecting page that already exists. Cheers - [[User:Sarah|Sarah]] ([[User talk:Sarah|talk]]) 05:53, 20 November 2014 (EST)

Thanks again Michael - Totally helpful. [[User:Sarah|Sarah]] ([[User talk:Sarah|talk]]) 21:01, 22 November 2014 (EST)

Hi Michael -- What do you suggest for referencing if I'm citing a textbook, as they don't have a simple PMID I can use? For example, for a lot of smear stuff I tend to refer to Dr. Joseph's book (Diagnostic Neuropathology Smears). Is there any way to use something like Mendeley Desktop to help with references? Ana [[User:Ana|Ana]] ([[User talk:Ana|talk]]) 08:10, 17 February 2015 (MST)

Neurodegenerative diseases

2015-02-16T18:36:12Z

Ana: /* Common diseases */

'''Neurodegenerative diseases''' is a big part of [[neuropathology]]. It includes some discussion of '''dementia'''.

=Overview=
*Neurodegenerative disease = essentially progressive and selective neuron loss.
*Clinically, they are not unique, e.g. dementia can be caused by several diseases (with different molecular etiologies).
**Each syndrome (e.g. dementia, parkinsonism, ataxia) has a most common etiology and a DDx.
*They are defined by molecular pathology.<ref name=pmid19918325>{{cite journal |author=Dickson DW |title=Neuropathology of non-Alzheimer degenerative disorders |journal=Int J Clin Exp Pathol |volume=3 |issue=1 |pages=1–23 |year=2009 |pmid=19918325 |pmc=2776269 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776269/?tool=pubmed}}</ref>
**The diseases are due to the accumulation of abnormal protein.
***The amino acid sequence of the protein may be completely normal. The problem may just be folding/protein conformation.

Molecular schema of neurodegenerative disorders:<ref name=pmid19918325/>
{{familytree/start}}
{{familytree | | | | | | | A01 | | | | | | | | A01=Neurodegenerative disorders}}
{{familytree | |,|-|-|-|v|-|^|-|v|-|-|-|.| | |}}
{{familytree | B01 | | B02 | | B03 | | B04 | |B01=Amyloidoses|B02=Tauopathies|B03=α-synucleinopathies|B04=TDP-43}}
{{familytree/end}}

===Common diseases===
[[Amyloid]]oses:
*Alzheimer disease (Abeta).

'Pure' tauopathies:
*[[Progressive supranuclear palsy]].
*[[Pick's disease]].
*Corticobasal degeneration
*FTDP-17
*Dementia pugilistica

Synucleinopathies:<ref name=pmid18855701>{{Cite journal | last1 = Uversky | first1 = VN. | title = Alpha-synuclein misfolding and neurodegenerative diseases. | journal = Curr Protein Pept Sci | volume = 9 | issue = 5 | pages = 507-40 | month = Oct | year = 2008 | doi = | PMID = 18855701 }}</ref>
*[[Parkinson disease]].
*Dementia with [[Lewy bodies]].
*[[Multiple system atrophy]].

TDP-43 proteinopathies:
*[[Amyotrophic lateral sclerosis]].
*Frontotemporal lobar degeneration

FUS proteinopathies:
*[[Amyotrophic lateral sclerosis]].
*Frontotemporal lobar degeneration

Prionopathies:
*Creutzfeldt-Jakob disease (PrP).

====Table====
Disease/pathology/clinical correlation based on ''Dickson'':<ref name=pmid19918325>{{cite journal |author=Dickson DW |title=Neuropathology of non-Alzheimer degenerative disorders |journal=Int J Clin Exp Pathol |volume=3 |issue=1 |pages=1–23 |year=2009 |pmid=19918325 |pmc=2776269 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776269/?tool=pubmed}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Disease
! Mutated protein
! Distribution
! Clinical
! Histology
! Image
|-
| [[Alzheimer disease]]
| Abeta (mutated ''APP'')
| corticolimbic, usu. spares occipital
| dementia
| plaques, neurofibrillary tangles
| [http://en.wikipedia.org/wiki/File:Cerebral_amyloid_angiopathy_-2a-_amyloid_beta_-_high_mag.jpg]
|-
| [[Creutzfeldt-Jakob disease]]
| PrPres (mutated PrP)
| cortical & basal ganglia
| dementia (rapid progression), movement disorder
| cytoplasmic vacuolization
| [http://en.wikipedia.org/wiki/File:SpongiformChangeCJD.jpg]
|-
| [[Progressive supranuclear palsy]]
| tau 4R
| basal ganglia, brainstem
| atypical parkinsonism with early gait instability, falls, and supranuclear gaze palsy
| tau-positive globose neurofibrillary tangles in neurons, tufted astrocytes, coiled bodies in oligodendrocytes
| Image?
|-
| [[Pick disease]]
| tau 3R
| corticolimbic
| dementia + focal cortical syndrome
| Pick body ???
| Image?
|-
| [[Parkinson disease]]
| alpha-synuclein
| brainstem
| parkinsonism
| Lewy bodies
| [http://firstaidteam.com/usmlerximages/v/USMLERxLewy+bodies.gif.html]
|-
| [[Dementia with Lewy bodies|Dementia with Lewy bodies]]
| alpha-synuclein
| corticolimbic, brainstem
| dementia + parkinsonism
| Lewy bodies
| [http://firstaidteam.com/usmlerximages/v/USMLERxLewy+bodies.gif.html]
|-
| [[Multiple system atrophy]]
| alpha-synuclein
| basal ganglia, brainstem, cerebellum
| parkinsonism, ataxia
| cytoplasmic inclusion in oligodendrocytes<ref>MUN. 15 November 2010.</ref>
| Image
|-
| [[Amyotrophic lateral sclerosis|Amyotrophic lateral sclerosis (ALS)]]
| TDP-43
| motor neurons
| spasticity, weakness
| histology?
| Image
|-
| Frontotemporal lobar degeneration (FTLD)
| TDP-43
| cortex, basal ganglia
| dementia, focal cortical syndromes
| histology?
| Image?
|- 
|}

=Immunohistochemistry=
===Alpha-synuclein===
Look for:
*Lewy bodies (seen in Parkinson's d., Dementia with Lewy bodies) = round cytoplasmic eosinophilic body +/- pale halo.

===Tau===
*AT8 = stains phosphorylated tau.<ref name=pmid19946779>{{cite journal |author=Seelaar H, Klijnsma KY, de Koning I, ''et al.'' |title=Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration |journal=J. Neurol. |volume=257 |issue=5 |pages=747–53 |year=2010 |month=May |pmid=19946779 |pmc=2864899 |doi=10.1007/s00415-009-5404-z |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864899/}}</ref>
**''AT'' = anti-tau.
**Stains tau 4R and tau 3R.<ref>{{cite journal |author=Kumaran R, Kingsbury A, Coulter I, ''et al.'' |title=DJ-1 (PARK7) is associated with 3R and 4R tau neuronal and glial inclusions in neurodegenerative disorders |journal=Neurobiol. Dis. |volume=28 |issue=1 |pages=122–32 |year=2007 |month=October |pmid=17719794 |doi=10.1016/j.nbd.2007.07.012 |url=}}</ref>

===TDP-43===
*May accumulate due to a ''progranulin mutation''.

====Microscopic====
*TDP-43 - normally in the nucleus.
**Pathologic: [http://archneur.ama-assn.org/cgi/content/full/65/5/636/NOC70108F2 Micrograph (label B) - neurites, skein-like formations (ama-assn.org)]<ref>{{cite journal |author=Geser F, Brandmeir NJ, Kwong LK, ''et al.'' |title=Evidence of multisystem disorder in whole-brain map of pathological TDP-43 in amyotrophic lateral sclerosis |journal=Arch. Neurol. |volume=65 |issue=5 |pages=636–41 |year=2008 |month=May |pmid=18474740 |doi=10.1001/archneur.65.5.636 |url=}}</ref>
***''Fibrillar'' or ''skein-like formations'' = cytoplasmic staining.
****"Skein" = ''yarn or thread wound on a reel'' or ''flock of birds in flight''.<ref>URL: [http://dictionary.reference.com/browse/skein http://dictionary.reference.com/browse/skein]. Accessed on: 20 November 2010.</ref>
***''Neurites'' = "squiggly appearance"; "worm-like appearance".

===Ubiquitin===
*Marks proteins for recycling.

====Microscopic====
*p62; poli-ubiquitin-binding protein p62.<ref name=pmid19946779/>

Look for:
*Lewy bodies. (???)

=Clinical perspective=
===Dementia general (mostly useless) DDx===
*[[Alzheimer's disease|Alzheimer's]] dementia - most common.
*Vascular.
**Multi-infarct dementia.
*Parkinson's associated dementia.
*Lewy body dementia.
*[[Alcohol]]-related dementia.
*Fronto-temporal dementia (Pick disease).
*Multisystem atrophy.

====Mnemonic====
Dementia mnemonic ''VITAMIN D VEST'':<ref name=Ref_TN2006_PS19>{{Ref TN2006| PS19}}</ref>
*Vitamin deficiency (B12, folate, thiamine).
*Infection (HIV).
*Trauma.
*Anoxia.
*Metabolic (Diabetes).
*[[CNS tumours|Intracranial tumour]].
*Normal pressure hydrocephalus.
*Degenerative (Alzheimer's, Huntington's, CJD).
*[[Vascular disease|Vascular]].
*Endocrine.
*Space occupying lesion (chronic subdural hematoma).
*Toxins (alcohol).

====Functional anatomy of dementia====
*[[Hippocampus]] (essential for forming new memories).
*Frontal lobe (essential for retrieval of memories).

===Parkinsonism causes===
*Parkinson's disease <ref name=pmid17390256>{{Cite journal | last1 = Tuite | first1 = PJ. | last2 = Krawczewski | first2 = K. | title = Parkinsonism: a review-of-systems approach to diagnosis. | journal = Semin Neurol | volume = 27 | issue = 2 | pages = 113-22 | month = Apr | year = 2007 | doi = 10.1055/s-2007-971174 | PMID = 17390256 }}</ref>
*Dementia with Lewy bodies.
*[[Multiple system atrophy]] (MSA).<ref name=pmid22074330>{{Cite journal | last1 = Ahmed | first1 = Z. | last2 = Asi | first2 = YT. | last3 = Sailer | first3 = A. | last4 = Lees | first4 = AJ. | last5 = Houlden | first5 = H. | last6 = Revesz | first6 = T. | last7 = Holton | first7 = JL. | title = Review: The neuropathology, pathophysiology and genetics of multiple system atrophy. | journal = Neuropathol Appl Neurobiol | volume = | issue = | pages = | month = Nov | year = 2011 | doi = 10.1111/j.1365-2990.2011.01234.x | PMID = 22074330 }}</ref>
*[[Progressive supranuclear palsy]] (PSP).<ref name=pmid22228724>{{Cite journal | last1 = Bertram | first1 = K. | last2 = Williams | first2 = DR. | title = Visual hallucinations in the differential diagnosis of parkinsonism. | journal = J Neurol Neurosurg Psychiatry | volume = 83 | issue = 4 | pages = 448-52 | month = Apr | year = 2012 | doi = 10.1136/jnnp-2011-300980 | PMID = 22228724 }}</ref>
*Drug induced (valproic acid).<ref name=pmid21993183>{{Cite journal | last1 = Mahmoud | first1 = F. | last2 = Tampi | first2 = RR. | title = Valproic Acid-Induced Parkinsonism in the Elderly: A Comprehensive Review of the Literature. | journal = Am J Geriatr Pharmacother | volume = | issue = | pages = | month = Oct | year = 2011 | doi = 10.1016/j.amjopharm.2011.09.002 | PMID = 21993183 }}</ref>

=Amyloidoses=
==Alzheimer disease==
===General===
*Onset: episodic memory loss.
*Diagnosis is clinical & pathologic.
**Pathologic finding alone are not diagnostic.
*Seen in conjunction with vascular amyloid deposition; see ''[[cerebral amyloid angiopathy]]''.

====Genetics====
Genes associated with Alzheimer disease:<ref>{{Ref PCPBoD8|674-5}}</ref>
*Amyloid precursor protein (APP).
**On chromosome 21 - may explain why [[Trisomy 21]] (Down syndrome) increases the risk of Alzheimer disease.<ref name=pmid19269132>{{Cite journal | last1 = Nieuwenhuis-Mark | first1 = RE. | title = Diagnosing Alzheimer's dementia in Down syndrome: problems and possible solutions. | journal = Res Dev Disabil | volume = 30 | issue = 5 | pages = 827-38 | month = | year = | doi = 10.1016/j.ridd.2009.01.010 | PMID = 19269132 }}</ref>
*Presenilin 1 (PSEN1).<ref name=omim104311>{{OMIM|104311}}</ref>
*Presenilin 2 (PSEN2).<ref name=omim600759>{{OMIM|600759}}</ref>
*Apolipoprotein E (APOE)<ref name=omim107741>{{OMIM|107741}}</ref> - specifically the ''epsilon-4'' allele.

===Gross===
Features:
*Temporal atrophy, esp. hippocampus.
*Dilation of:
**Lateral ventricles.
**Third ventricle.

Gross/microscopic - disease spread by NF tangles (staging):<ref name=pmid8307060>{{cite journal |author=Braak H, Braak E, Bohl J |title=Staging of Alzheimer-related cortical destruction |journal=Eur. Neurol. |volume=33 |issue=6 |pages=403–8 |year=1993 |pmid=8307060 |doi= |url=}}</ref>
*Alzheimer "spreads" in a reproducible pattern:
**Stage I-II: entorhinal cortex.
**Stage III-IV: inferior aspect of brain.
**Stage V-VI: limbic system.

===Microscopic===
Features:
#Neurofibrillary tangles.
#*Consists of ''tau''.
#*Location: hippocampus, cerebral cortex, hypothalamus.
#*Images: [http://www.pakmed.net/academic/age/alz/plaques_tanglesBorder.jpg tangles - schematic (pakmed.net)]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>, [http://faculty.washington.edu/alexbert/MEDEX/Fall/adtangle.jpg tangle (washington.edu)].<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
#*Dementia severity correlates better with NF tangles number than senile plaque number.<ref>{{Ref PBoD8|1317}}</ref>
#Senile plaques ([[AKA]] neuritic plaques).
#*Consists of two components:
#*#Centre - radiates.
#*#*Consists of Abeta amyloid
#*#Neurites - swollen axons.
#*Considered to be more specific for Alzheimer's than NF tangles.
#**How to remember: '''s'''enile '''p'''laques = '''sp'''ecific.
#*There is a staging system for plaques I (mild), II (moderate), III (severe).
#*Images: [http://library.med.utah.edu/WebPath/jpeg5/CNS091.jpg senile plaques (utah.edu)]<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html]. Accessed on: 5 December 2010.</ref> [http://commons.wikimedia.org/wiki/File:Cerebral_amyloid_angiopathy_-2a-_amyloid_beta_-_high_mag.jpg senile plaques - beta-APP - high mag. (WC)].
#Neuron loss.
#+/-[[Cerebral amyloid angiopathy]].

Notes:
*Abeta amyloid:
**Derived from ''amyloid precursor protein'' (APP).
***APP:
****Rapid axonal transport - useful as a marker of axonal injury.
****Function currently not known.
*Tau:
**Important in microtubule assembly.

==Prion diseases==
===General===
Etiology:<ref name=pmid16609731>{{cite journal |author=Watts JC, Balachandran A, Westaway D |title=The expanding universe of prion diseases |journal=PLoS Pathog. |volume=2 |issue=3 |pages=e26 |year=2006 |month=March |pmid=16609731 |pmc=1434791 |doi=10.1371/journal.ppat.0020026 |url=}}</ref>
*Misfolded cell-surface protein called PrPSC.
**This is derived from the protein ''PrPC'' encoded by the ''PRNP'' gene.

Includes:
*Creutzfeldt-Jakob disease (CJD).
*Sporadic fatal insomnia (sFI).<ref name=pmid16609731>{{cite journal |author=Watts JC, Balachandran A, Westaway D |title=The expanding universe of prion diseases |journal=PLoS Pathog. |volume=2 |issue=3 |pages=e26 |year=2006 |month=March |pmid=16609731 |pmc=1434791 |doi=10.1371/journal.ppat.0020026 |url=}}</ref>
*Fatal familial insomnia (FFI).<ref name=Ref_PCPBoD8_672>{{Ref PCPBoD8|672}}</ref><ref name=omim600072>{{OMIM|600072}}</ref>
*Gestmann-Straussler-Scheinker syndrome (GSS) - due to PRNP gene mutations.<ref name=Ref_PCPBoD8_671>{{Ref PCPBoD8|671}}</ref>

===IHC===
PrPC:<ref name=Ref_PCPBoD8_672>{{Ref PCPBoD8|672}}</ref>
*Congo red +ve.
*PAS +ve.

==Creutzfeldt-Jakob disease==
*Commonly abbreviated as ''CJD''.
===General===
*Rare.
*Incurable disease.

Usually diagnosed clinically:
*Characteristic findings:
**Very rapid decline (3-4 months).
**Characteristic (cortex findings on) neuroradiology.

====Variant Creutzfeldt-Jakob disease====
*Abbreviated ''vCJD''.
=====General=====
*Associated with ''bovine spongiform encephalopathy'' ([[AKA]] ''mad cow disease'').
*Should sample: [[spleen]], [[lymph node]]s, tonsils.<ref name=Ref_HospAuto83>{{Ref HospAuto|83}}</ref>

===Microscopic===
Features:
*Spongy appearance (cytoplasmic vacuolization<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0I002-PQ01-M.htm http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0I002-PQ01-M.htm]. Accessed on: 19 October 2010.</ref>).

Note:
*Spongiform changes may be seen in [[ALS]], [[Alzheimer's disease]] and Lewy body disease (e.g. [[Parkinson disease]]); however, the changes are only in the upper cortex and not diffuse.<ref>{{Ref APBR|419 Q4}}</ref>

Images:
*[http://commons.wikimedia.org/wiki/File:SpongiformChangeCJD.jpg CJD (WC)].
*[http://commons.wikimedia.org/wiki/File:VCJD_Tonsil.jpg vCJD - IHC (WC)].
*[http://path.upmc.edu/cases/case86.html CJD - several cases (upmc.edu)].

=Alpha-synucleinopathies=
Includes the Lewy body diseases [[Parkinson's disease]] and [[Dementia with Lewy bodies]].

==Dementia with Lewy bodies==
===General===
Clinical features:
*Parkinsonian features.
*Hallucinations (visual).
*Progressive cognitive decline with fluctuations.

===Microscopic===
Features:
*[[Lewy bodies]].

===IHC===
*Alpha-synuclein +ve.

==Parkinson disease==
===General===
*Common - often sporadic.
*May be genetic.

Clinical ''TRAP'':<ref>URL: [http://www.nysslha.org/i4a/pages/index.cfm?pageid=3519 http://www.nysslha.org/i4a/pages/index.cfm?pageid=3519]. Accessed on: 30 March 2011.</ref>
*Tremor.
*Rigidity.
*Akinesia.
*Postural instability.

Genetics:<ref name=Ref_PCPBoD8_677>{{Ref PCPBoD8|677}}</ref>
*LRRK2 gene<ref name=omim609007>{{OMIM|609007}}</ref> - autosomal dominant.
*PARK2 gene (parkin)<ref name=omim602544>{{OMIM|602544}}</ref> - autosomal recessive.

===Gross===
Features:<ref name=Ref_PBoD8_1319>{{Ref PBoD8|1319}}</ref>
*Abnormally pale substantia nigra.
**Pigmentation increases with age.
*Pale ''[[locus ceruleus]]''.

Notes:
*Substantia nigra is a midbrain structure.
**Image: [http://commons.wikimedia.org/wiki/File:Midbraincrosssection.png Midbrain - schematic (WC)].

===Microscopic===
Features:<ref name=Ref_PBoD8_1319>{{Ref PBoD8|1319}}</ref>
*Loss of pigmented (catecholaminergic) neurons in the substantia nigra and locus ceruleus.
*Gliosis - due to neuron loss.
*[[Lewy bodies]] (in remaining neurons) - '''key feature'''.
**Eosinophilic cytoplasmic inclusion with "dense" (darker) core and pale (surrounding) halo.
***Consist of filaments composed of alpha-synuclein.

===IHC===
*Alpha-synuclein +ve.

==Multiple system atrophy==
===General===
Clinical findings variable:
*Parkinsonism (stiatonigral degeneration).
*Ataxia (olivo-panto-cerebellar degeneration).

===Microscopic===
Features:
*Alpha-synuclein-rich glial cytoplasmic inclusions (finding at autopsy).<ref name=pmid18825660>{{Cite journal | last1 = Wenning | first1 = GK. | last2 = Stefanova | first2 = N. | last3 = Jellinger | first3 = KA. | last4 = Poewe | first4 = W. | last5 = Schlossmacher | first5 = MG. | title = Multiple system atrophy: a primary oligodendrogliopathy. | journal = Ann Neurol | volume = 64 | issue = 3 | pages = 239-46 | month = Sep | year = 2008 | doi = 10.1002/ana.21465 | PMID = 18825660 }}</ref>
**Inclusions in oligodendrocytes.<ref>MUN. 16 November 2010.</ref>

=Tauopathies=
==Progressive supranuclear palsy==
*Commonly abbreviated ''PSP''.
*[[AKA]] ''Steele-Richardson-Olszewski syndrome''.
===General===
*Diagnosis - clinical.<ref name=psp_emedicine>URL: [http://emedicine.medscape.com/article/1151430-overview http://emedicine.medscape.com/article/1151430-overview]. Accessed on: 11 November 2010.</ref>

Clinical:
*Impaired control of gaze, esp. difficulty looking up and down (supranuclear palsy).<ref name=pmid21690028>{{Cite journal | last1 = Levy | first1 = R. | title = [Progressive supranuclear palsy: what's new?]. | journal = Geriatr Psychol Neuropsychiatr Vieil | volume = 9 | issue = 2 | pages = 191-201 | month = Jun | year = 2011 | doi = 10.1684/pnv.2011.0271 | PMID = 21690028 }}</ref>
*Parkinsonism.<ref name=pmid22228724>{{Cite journal | last1 = Bertram | first1 = K. | last2 = Williams | first2 = DR. | title = Visual hallucinations in the differential diagnosis of parkinsonism. | journal = J Neurol Neurosurg Psychiatry | volume = 83 | issue = 4 | pages = 448-52 | month = Apr | year = 2012 | doi = 10.1136/jnnp-2011-300980 | PMID = 22228724 }}</ref>

===Microscopic===
Features:<ref name=pmid19918325>{{cite journal |author=Dickson DW |title=Neuropathology of non-Alzheimer degenerative disorders |journal=Int J Clin Exp Pathol |volume=3 |issue=1 |pages=1–23 |year=2009 |pmid=19918325 |pmc=2776269 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776269/?tool=pubmed}}</ref><ref name=psp_emedicine>URL: [http://emedicine.medscape.com/article/1151430-overview http://emedicine.medscape.com/article/1151430-overview]. Accessed on: 11 November 2010.</ref><ref name=pmid19233037>{{cite journal |author=Williams DR, Lees AJ |title=Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges |journal=Lancet Neurol |volume=8 |issue=3 |pages=270–9 |year=2009 |month=March |pmid=19233037 |doi=10.1016/S1474-4422(09)70042-0 |url=}}</ref>
*Globose neurofibrillary tangles in neurons.
*Coiled bodies in oligodendrocytes.
**Wire coil-like structure around the nucleus.
*Tufted astrocytes.
**Near impossible to see without [[IHC]] - specifically AT8.
**Cellular processes filled with crap.
**Star-like appearance; looks like a road network where all the roads lead to one place (Parisian star).
*Grumose degeneration of the cerebellar dentate nucleus.
**Granular eosinophilic material adjacent to nuclei; once thought to be pathognomonic for PSP.<ref>URL: [http://neuropathologyblog.blogspot.com/2008/03/grumose-degeneration-in-cerebellar.html http://neuropathologyblog.blogspot.com/2008/03/grumose-degeneration-in-cerebellar.html]. Accessed on: 4 December 2010.</ref><ref>{{cite journal |author=Yamanouchi H, Yokoo H, Yuhara Y, ''et al.'' |title=An autopsy case of ornithine transcarbamylase deficiency |journal=Brain Dev. |volume=24 |issue=2 |pages=91–4 |year=2002 |month=March |pmid=11891099 |doi= |url=}}</ref>

Images:
*[http://path.upmc.edu/cases/case238/micro.html PSP - several images (upmc.edu)].

==Pick disease==
===General===
*Dementia.

===Gross===
*Frontal and temporal lobe atrophy.<ref name=Ref_PCPBoD8_676>{{Ref PCPBoD8|676}}</ref>
**May be called "walnut brain"<ref>URL: [http://medical-dictionary.thefreedictionary.com/Walnut+Brain http://medical-dictionary.thefreedictionary.com/Walnut+Brain]. Accessed on: 14 March 2012.</ref> - as it resembles a walnut.

===Microscopic===
Features:<ref name=Ref_PCPBoD8_676>{{Ref PCPBoD8|676}}</ref>
*Pick cells = large ballooned neurons.
*Pick bodies = round, homogenous, intracytoplasmic inclusions, size ~10 micrometers.

Image(s):
*[http://www.nature.com/nrneurol/journal/v6/n2/fig_tab/nrneurol.2009.216_F1.html Pick body (nature.com)].<ref name=pmid20139998>{{Cite journal | last1 = Grossman | first1 = M. | title = Primary progressive aphasia: clinicopathological correlations. | journal = Nat Rev Neurol | volume = 6 | issue = 2 | pages = 88-97 | month = Feb | year = 2010 | doi = 10.1038/nrneurol.2009.216 | PMID = 20139998 }}</ref>

=Other=
==Chronic traumatic encephalopathy==
*Abbreviated ''CTE''.
===General===
*Due to head trauma - usually repetitive.
**Seen in ''American football'' and ''boxing''.
***The in the context of boxing it is known as ''dementia pugilistica''; ''pugil'' is ''boxer'' in Latin.<ref>URL: [http://dictionary.reference.com/browse/pugilism http://dictionary.reference.com/browse/pugilism]. Accessed on: 21 November 2011.</ref>
*May be associated with motor neuron disease.<ref name=pmid22050943>{{Cite journal | last1 = Daneshvar | first1 = DH. | last2 = Riley | first2 = DO. | last3 = Nowinski | first3 = CJ. | last4 = McKee | first4 = AC. | last5 = Stern | first5 = RA. | last6 = Cantu | first6 = RC. | title = Long-term consequences: effects on normal development profile after concussion. | journal = Phys Med Rehabil Clin N Am | volume = 22 | issue = 4 | pages = 683-700 | month = Nov | year = 2011 | doi = 10.1016/j.pmr.2011.08.009 | PMID = 22050943 }}</ref>

===Microscopic===
Features:<ref name=pmid22035690>{{Cite journal | last1 = Stern | first1 = RA. | last2 = Riley | first2 = DO. | last3 = Daneshvar | first3 = DH. | last4 = Nowinski | first4 = CJ. | last5 = Cantu | first5 = RC. | last6 = McKee | first6 = AC. | title = Long-term Consequences of Repetitive Brain Trauma: Chronic Traumatic Encephalopathy. | journal = PM R | volume = 3 | issue = 10 Suppl 2 | pages = S460-7 | month = Oct | year = 2011 | doi = 10.1016/j.pmrj.2011.08.008 | PMID = 22035690 }}</ref>
*Wall-to-wall neurofibrillary tangles.
**Common in olfactory bulb, mammillary bodies, hippocampus.
**Usually perivascular.
**Often superficial (unlike [[Alzheimer disease]]) and at the deep aspect of sulci.

===IHC===
*Increased TDP-43 staining.

Note:
*[[ALS]] associated with trauma brain injuries.<ref name=pmid21696410>{{Cite journal | last1 = Costanza | first1 = A. | last2 = Weber | first2 = K. | last3 = Gandy | first3 = S. | last4 = Bouras | first4 = C. | last5 = Hof | first5 = PR. | last6 = Giannakopoulos | first6 = P. | last7 = Canuto | first7 = A. | title = Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates. | journal = Neuropathol Appl Neurobiol | volume = 37 | issue = 6 | pages = 570-84 | month = Oct | year = 2011 | doi = 10.1111/j.1365-2990.2011.01186.x | PMID = 21696410 }}</ref>

==Huntington disease==
===General===
*Autosomal dominant inheritance.
*Mutation in ''Huntington gene'' (HTT):<ref name=pmid20360611>{{cite journal |author=Kumar P, Kalonia H, Kumar A |title=Huntington's disease: pathogenesis to animal models |journal=Pharmacol Rep |volume=62 |issue=1 |pages=1–14 |year=2010 |pmid=20360611 |doi= |url=}}</ref>
**11-34 CAG repeat = normal.<ref name=omim613004>{{OMIM|613004}}</ref>
**>42 CAG repeat = Huntington disease.

Clinical:<ref name=Ref_APBR415>{{Ref APBR|415 Q44}}</ref>
*Early onset dementia.
*Involuntary movements (chorea) - both arms and legs.
*Behaviour changes, e.g. grimacing.
*Speech changes.

===Gross===
*Severe caudate atrophy.<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/NeuroTest/Q07-Ans.htm http://moon.ouhsc.edu/kfung/jty1/NeuroTest/Q07-Ans.htm]. Accessed on: 29 October 2010.</ref>
**Prominent frontal horns of the lateral ventricles.<ref>URL: [http://path.upmc.edu/cases/case117/gross.html http://path.upmc.edu/cases/case117/gross.html]. Accessed on: 3 January 2012.</ref>

Note:
*A normal caudate bulges into the ventricle.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/NeuroTest/Q07-Ans.htm Huntington's disease (ouhsc.edu)].
*[http://path.upmc.edu/cases/case117/gross.html Prominent frontal horns of the lateral ventricles (upmc.edu)].

===Microscopic===
Features:<ref name=Ref_APBR415>{{Ref APBR|415 Q44}}</ref>
*Neuron loss.
*Gliosis.

==Binswanger disease==
===General===
*Multi-infarct dementia affecting subcortical white matter.
*Waste-basket diagnosis; diagnosed if [[CADASIL]] and [[amyloidosis]] have been excluded.
*Diagnosis has been controversial -- most with this entity (in the past) were diagnosed with ''[[Alzheimer's disease]]''.

===Microscopic===
Features:
*Subcortical lesions that replace the myelin consisting of macrophages.

==Frontotemporal lobar degeneration with ubiquitinated inclusions==
Abbreviated ''FTLD with ubiquitinated inclusions'' or ''FTLD-TDP43''.
===General===
*There are several forms of ''frontotemporal dementia''.
*Related to [[amyotrophic lateral sclerosis]] (ALS); also a TDP-43 pathology.<ref>{{OMIM|105400}}</ref>
**There are several subtypes of FTLD with TDP-43.

===Gross===
*Frontal and temporal lobe atrophy.

Image:
*[http://commons.wikimedia.org/wiki/File:Frontotemporal_degeneration.png FTLD (WC)].

==Amyotrophic lateral sclerosis==
*Abbreviated ''ALS''.
===General===
*[[AKA]] Lou Gehrig's disease.
*TDP-43 proteinopathy.
*Characterized by motor neuron death.
*May be familial and associated with ''SOD1'' gene.<ref name=Ref_PCPBoD8_679>{{Ref PCPBoD8|679}}</ref>

Clinical:
*Weakness.

===Microscopic===
Features:<ref name=Ref_PCPBoD8_679>{{Ref PCPBoD8|679}}</ref>
*Motor neurons with ''Bunina bodies''.
**PAS positive cytoplasmic inclusions.
*Motor neuron loss + reactive gliosis + neurogenic muscular atrophy.

Images:
*[http://jsp.umin.ac.jp/corepictures2007/18/o02/index.html Bunina body (umin.ac.jp)].
*[http://pathology.mc.duke.edu/neuropath/CNSlecture4/alsbunina.jpg Bunina body (duke.edu)].<ref>URL: [http://pathology.mc.duke.edu/neuropath/CNSlecture4/CNSlecture4.htm http://pathology.mc.duke.edu/neuropath/CNSlecture4/CNSlecture4.htm]. Accessed on: 30 August 2011.</ref>
*[http://path.upmc.edu/cases/case291.html ALS - several images (upmc.edu)].

==Hallervorden-Spatz disease==
*[[AKA]] ''pantothenate kinase-associated neurodegeneration''.

===General===
*Uncommon.

===Microscopic===
Features:<ref>URL: [http://path.upmc.edu/cases/case207/dx.html http://path.upmc.edu/cases/case207/dx.html]. Accessed on: 11 January 2012.</ref>
*Axonal spheroids.
*Iron deposition.

Images:
*[http://path.upmc.edu/cases/case207.html HSD - several images (upmc.edu)].

===Stains===
*Prussian blue +ve.

=See also=
*[[Neuropathology]].
*[[Neurohistology]].

=References=
{{Reflist|2}}

[[Category:Neuropathology]]

Neuropathology

2015-02-16T18:31:01Z

Ana: /* Table of inclusions */

[[Image:MCA-Stroke-Brain-Human-2.JPG|thumb|right|Gross image showing changes of a [[stroke]]. (WC/Marvin 101)]]
This article is an introduction to '''neuropathology'''. There are separate articles for [[brain tumours]], the [[pituitary gland]], the [[spine]], the [[eye]], [[muscle pathologies]], [[neurohistology]] and [[neuroanatomy]].

Neuropathology is the bane of many anatomical pathologists in teaching hospitals... 'cause they have to fill in for the neuropathologist when he or she is on vacation.

==Neuroanatomy==
{{Main|Neuroanatomy}}
This is a large topic. It covered in a separate article, that also covers grossing.

==Neuroradiology==
Key factors to consider in evaluation:
# location
# number of lesions - single vs. multiple
# cystic vs. solid lesion
# enhancement

==Lesion location==
In neuroradiology and neuropathology, real estate is crucial. Lesion location can often narrow your differential.

Cortical lesions (gray matter):
* oligodendroglioma
* DNET
* ganglioglioma
* pleomorphic xanthoastrocytoma
* extraventricular ependymoma

Cortical-subcortical junction:
* metastases
* abscesses (hematogenous spread)

Subcortical lesions (white matter):
* glioblastoma
* diffuse gliomas
* demyelinating plaques

Deep gray matter lesions (e.g. basal ganglia);
* gliomas
* hypertensive hemorrhage

Cerebellar lesions:
* medulloblastoma
* pilocytic astrocytoma
* AT/RT

Intraventricular lesions:
* ependymoma
* subependymoma
* pilocytic astrocytoma
* central neurocytoma
* rosette forming glioneuronal tumour of the fourth ventricle

Suprasellar (above the pituitary):
* craniopharyngioma
* germinoma
* pilomyxoid astrocytoma

==Number of lesions==
If ''single'' lesion = think primary, neoplastic
If ''multiple'' lesions = think metastatic, neoplastic or infectious
'''NB: glioblastoma can be multifocal''' (and the foci can be quite far apart)

==Cystic vs. solid lesions==
Some tumours are classically cystic with a small solid component (so-called cyst with a mural nodule) -- e.g. pilocytic astrocytoma, ganglioglioma, hemangioblastoma

==Enhancing vs. non-enhancing:==
*In adults, enhancing generally = high grade.
*In pediatrics, it often depends on the pattern.
Two main patterns to be mindful of -- ring enhancing lesions, and cystic lesions with a mural nodule.

===Ring enhancing lesions===
In [[HIV]]/AIDS patients... mass on CT if infection:
*[[Toxoplasmosis]] - most common.<ref>MUN. Feb 3, 2009.</ref>

Ring enhancing lesion (DDx) - mnemonic ''MAGICAL DR'':<ref>{{Ref TN2005 |NS7}}</ref>
*Metstasis.
*Abscess.
*[[Glioblastoma]].
*[[Infarct]].
*Contusion.
*AIDS-related.
*[[Lymphoma]] + [[HIV]] assoc. disease (toxoplasma).
*Demyelination (e.g. [[multiple sclerosis]]).
*Resolving hematoma.

===Cyst with enhancing mural nodule===
*hemangioblastoma (#1 in adults)
*pilocytic astrocytoma (#1 in peds)
*pleomorphic xanthoastrocytoma
*ganglioglioma

==Grossing==
This is covered in the ''[[neuroanatomy]]'' article.

===Gross pathology===
The gross usually useless for arriving at a definitive diagnosis.

Exceptions:<ref>R. Kiehl. 8 November 2010.</ref>
*Sausage shape lesion of filum terminale = [[myxopapillary ependymoma]].
*Soft & tan colour = [[pituitary adenoma]].

==Normal histology==
{{main|Neurohistology}}
This is a big topic. It is covered in a separate article called ''[[neurohistology]]''.

==Histopathology==
===Neuronal changes===
====Anoxic neurons====
*[[AKA]] ''red neurons''.

Features:
*Intensely red cytoplasm.
*Pyknosis = nuclear shrinkage + darker staining.

=====Images=====
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons (WC)
Image:AcuteStroke_HE400x.jpg | Neurons in an acute stroke. (WC)
</gallery>
www:
*[http://neuropathology-web.org/chapter2/images2/2-anoxic.png Anoxic neurons (neuropathologyweb.org)].<ref>URL: [http://neuropathology-web.org/chapter2/chapter2aHIE.html http://neuropathology-web.org/chapter2/chapter2aHIE.html]. Accessed on: 10 December 2014.</ref>
*[http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-16.gif Anoxic neurons (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>

====Central chromatolysis====
Features:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html]. Accessed on: 22 December 2010.</ref>
*Central clearing.
**Nucleus and Nissl substance are pushed to cell periphery.

DDx:
*Axonal injury (traumatic).<ref name=pmid8909880>{{cite journal |author=Holland GR |title=Experimental trigeminal nerve injury |journal=Crit. Rev. Oral Biol. Med. |volume=7 |issue=3 |pages=237–58 |year=1996 |pmid=8909880 |doi= |url=}}</ref>
*Vitamin deficiency ([[pellagra]]).<ref name=pmid15577526>{{cite journal |author=Piercecchi-Marti MD, Pélissier-Alicot AL, Leonetti G, Tervé JP, Cianfarani F, Pellissier JF |title=Pellagra: a rare disease observed in a victim of mental and physical abuse |journal=Am J Forensic Med Pathol |volume=25 |issue=4 |pages=342–4 |year=2004 |month=December |pmid=15577526 |doi= |url=}}</ref>

=====Images=====
<gallery>
Image:Central_chromatolysis_-_intermed_mag_-_cropped.jpg | Central chromatolysis - intermed. mag. (WC)
Image:Central_chromatolysis_-_nf_-_very_high_mag.jpg | Central chromatolysis - NF stain - very high mag. (WC)
</gallery>
====Axonal swellings====
H&E:
*Eosinophilic (light pink) - ground glass-like appearance.
*Shape:
**Round if sectioned perpendicular to axis of axon.
***Bound by cell membrane.
***Large ~ typically 2-4x RBC diameter.
**Sausage-shaped if cut in along axis.

Images:
*[http://frontalcortex.com/gallery/pics/gliageek_VWMDx200.jpg Axonal swelling (frontalcortex.com)].<ref>URL: [http://frontalcortex.com/?page=oll&topic=24&qid=602 http://frontalcortex.com/?page=oll&topic=24&qid=602]. Accessed on: 3 November 2010.</ref>
*[http://www.neuropathologyweb.org/chapter3/images3/3-pvlaxonsweling.jpg Axonal swelling (neuropathologyweb.org)].

=====IHC=====
*APP.

Image:
*[http://vet.sagepub.com/content/37/6/677/F7.expansion.html Axonal swelling - APP (sagepub.com)].<ref>{{cite journal |author=Finnie JW, Manavis J, Blumbergs PC, Kuchel TR |title=Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin |journal=Vet. Pathol. |volume=37 |issue=6 |pages=677–80 |year=2000 |month=November |pmid=11105962 |doi= |url=http://vet.sagepub.com/content/37/6/677.full}}</ref>

===Glial changes===
====Astrocyte changes====
Reactive astrocytes:
*Approximately equally-spaced; distance between neighbouring astrocytes is ~2x (or more) the cell size.
*Well-defined cell border.
*Eosinophilic cytoplasm with many branching processes.
**Classically described as "funnel-shaped" in benign astrocytes.<ref>MUN. 15 November 2010.</ref>
*Peripheral nucleus.
<gallery>
Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg | Reactive astrocytes - high mag. (WC)
</gallery>

Alzheimer type II astrocyte:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 2 July 2010.</ref>
*Large cleared nucleus - '''key feature'''.
*Indistinct cytoplasm.
*Found in the context of ''hepatic encephalopathy'' in basal ganglia and lower layers of cortex.<ref name=Ref_Klatt202>{{Ref Klatt|202}}</ref>
*Images:
**[http://neuroquiz.com/?page=image&topic=1&qid=2714 Alzheimer type II astrocytes (neuroquiz.com)].
**[http://www.neuropathologyweb.org/chapter10/images10/10-AlzIIl.jpg Alzheimer type II astrocytes (neuropathologyweb.org)] .
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag.jpg| Alzheimer type II astrocytes. (WC)
</gallery>

Creutzfeldt cell:<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
*Finding associated with demyelinating disease.
*Image: [http://path.upmc.edu/cases/case336/images/fig03.jpg Crutzfeldt cell (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case336.html http://path.upmc.edu/cases/case336.html]. Accessed on: 15 January 2012.</ref>

Gemistocytic astrocytes:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 7 November 2010.</ref>
*Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:<ref name=Ref_MBNP173>{{Ref MBNP|173}}</ref>
*Cellular processes loaded with tau protein (as may be seen with tau [[IHC]] or Gallyas silver stain); Parisian-star-like appearance with special stain.
*+/-Multinucleated.
*A classic feature of ''[[progressive supranuclear palsy]]''.

====Other glial====
Bergmann gliosis (in the cerebellum):<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Thin layer of cells (2-3 cells) with open nuclei that are larger than granular cell layer nuclei; seen with Purkinje cell loss.

<gallery>
Image:Bergmann_gliosis_-_intermed_mag.jpg | Bergmann gliosis - intermed. mag. (WC)
Image:Bergmann_gliosis_-_high_mag.jpg | Bergmann gliosis - high mag. (WC)
Image:Metastatic_adenocarcinoma_-_cerebellum_-_intermed_mag.jpg | Bergmann gliosis due to compression by metastasis - intermed mag. (WC)
</gallery>
Image:
*[http://tpx.sagepub.com/content/35/5/676/F5.expansion.html Bergmann gliosis (sagepub.com)].

====Reactive change vs. malignancy====
Reactive changes vs. malignancy (mnemonic ''MIMICS''):<ref name=Ref_TPoSP254>{{Ref TPoSP|254}}</ref>
*'''MI'''crovesicular pattern.
*'''M'''itoses.
*'''I'''rregular spacing.
*'''C'''alcifications.
*'''S'''atellitosis, perineuronal.
**Large "crowds" of glial cells associated with nuclei.

===Inflammatory===
DDx:
*Autoimmune - [[Multiple sclerosis]].
*Neoplastic - [[Neuropathology tumours#CNS lymphoma|CNS lymphoma]].
*Infectious - [[HSV]].

====Encephalitis====
=====General=====
DDx:
*Viral encephalitis.
*Paraneoplastic syndromes.

=====Gross=====
*Frontal and temporal lobe - most common for HSV encephalitis.<ref>{{Ref APBR|416 Q47}}</ref>

=====Microscopic=====
Features:<ref name=pmid20051019>{{Cite journal | last1 = Takei | first1 = H. | last2 = Wilfong | first2 = A. | last3 = Malphrus | first3 = A. | last4 = Yoshor | first4 = D. | last5 = Hunter | first5 = JV. | last6 = Armstrong | first6 = DL. | last7 = Bhattacharjee | first7 = MB. | title = Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of the literature. | journal = Neuropathology | volume = 30 | issue = 4 | pages = 381-91 | month = Aug | year = 2010 | doi = 10.1111/j.1440-1789.2009.01079.x | PMID = 20051019 }}</ref>
*Perivascular inflammation.
*Microglia.
*+/-Neuronophagia.
**Phagocytosis of neurons.<ref>URL: [http://medical-dictionary.thefreedictionary.com/neuronophagia http://medical-dictionary.thefreedictionary.com/neuronophagia]. Accessed on: 11 April 2012.</ref>
*+/-Viral cytopathic changes.
*+/-Perineuronal inflammation.

Notes:
*Hemorrhage<ref name=pmid18246335>{{Cite journal | last1 = Vossough | first1 = A. | last2 = Zimmerman | first2 = RA. | last3 = Bilaniuk | first3 = LT. | last4 = Schwartz | first4 = EM. | title = Imaging findings of neonatal herpes simplex virus type 2 encephalitis. | journal = Neuroradiology | volume = 50 | issue = 4 | pages = 355-66 | month = Apr | year = 2008 | doi = 10.1007/s00234-007-0349-3 | PMID = 18246335 }}</ref> and necrosis - characteristic of HSV encephalitis.

Image:
*[http://neuropathology-web.org/chapter5/images5/5-21l.jpg HSV encephalitis (neuropathology-web.org)].<ref>URL: [http://neuropathology-web.org/chapter5/chapter5dViruses.html http://neuropathology-web.org/chapter5/chapter5dViruses.html]. Accessed on: 27 January 2012.</ref>

=====IHC=====
IHC stains for:
*Viral etiologies, e.g. [[HSV]], [[CMV]].
*Parasites, e.g. [[toxoplasma]].
*[[Fungi]], e.g. PASD.

===Architecture===
====Rosettes====
*Rosette = circular/flower-like arrangement of cells.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>

*Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**[[Ependymoma]].
**[[Medulloblastoma]], PNET.
**[[Central neurocytoma]].
**[[Glioblastoma]]s.

*Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**Medulloblastoma.
***Image: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Images/N1-TU-01-17.gif Medulloblastoma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17 http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17]. Accessed on: 3 December 2010.</ref>
**PNET (can be thought of as a supratentorial medulloblastoma) .

*Flexner-Wintersteiner rosette = rosette with empty centre (donut hole).<ref name=pmid16551982/>
**[[Retinoblastoma]]s.
**Pineoblastomas.
**Medulloepitheliomas.

*True ependymal rosette = surrounds a space.<ref name=pmid16551982/>
**[[Ependymoma]].

*Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**Similar to Homer-Wright rosette.
**[[Pineocytoma]].
**[[Neurocytoma]].

====Other====
*Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
**Key feature: variable thickness; helps separate from RBCs.
**Well-seen on trichrome stains.
<gallery>
Image:Rosenthal_HE_40x.jpg | Rosenthal fibres. (WP)
Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear (WC/AFIP)
</gallery>
*Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.<ref>{{Ref MBNP|11}}</ref>
**Image: [Image:Pilocytic_Micro.jpg EGBs (WC/AFIP)].
*Pseudopalisading - picket fence-like alignment of cells; long axis of cells perpendicular to interface with other structures/cells.
**Pseudopalisading of tumour cells (around necrotic regions) is seen in [[glioblastoma]].

Note:
*Good set of articles: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=Neuropathology%20for%20the%20neuroradiologist Neuropathology for radiologists (ncbi.nlm.nih.gov)].

===Inclusion bodies===
*Negri bodies.
**Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
**[[Rabies]].
<gallery>
Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg | Negri bodies. (WC/CDC)
</gallery>

*Lewy bodies.
**Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.<ref name=pmid15235805>{{cite journal |author=Marui W, Iseki E, Kato M, Akatsu H, Kosaka K |title=Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease |journal=Acta Neuropathol. |volume=108 |issue=2 |pages=121–8 |year=2004 |month=August |pmid=15235805 |doi=10.1007/s00401-004-0869-4 |url=}}</ref>
<gallery>
Image:Lewy_Koerperchen.JPG | Lewy body. (WC)
</gallery>
====Table of inclusions====
{| class="wikitable sortable"
! Feature
! Appearance
! Associated disease
! Comment
! Image
|-
| Grumose bodies [[AKA]] granular bodies
| granular and eosinophilic ~50 micrometers
| neurodegenerative disease, neuroaxonal dystrophies, aging
| ?Comment
| ?Image
|-
| Cowdry type 1 AKA Cowdry type A
| eosinophilic & round + halo
| [[herpes simplex virus]]
| can be confused with Lewy body, Marinesco body
| ?Image
|-
| Lewy body
| round cytoplasmic eosinophilic body +/- pale halo
| [[Parkinson disease]], dementia with Lewy bodies
| morphology dependent on location in brain; +ve for alpha-synuclein, alpha-B crystallin, ubiquitin
| [[Image:Lewy_Koerperchen.JPG |thumb|center|150px|]], [http://firstaidteam.com/usmlerximages/v/USMLERxLewy+bodies.gif.html]
|-
| Lafora body
| round
| myoclonic [[epilepsy]]
| look like corpora amylacea; location: dentate nucleus, liver, skeletal muscle, sweat glands
| ?Image
|-
| Lipofuscin
| yellow & granular
| aging
| olive, dendate
| ?Image
|-
| Negri body
| small eosinophic bodies
| rabies
| found in hippocampal neurons and Purkinje cells
| [[Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg|thumb|center|150px|]]
|-
| Hirano body
| concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron
| Alzheimer disease, Pick disease<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| actin crystals, may look like capillaries; location: CA1 of hippocampus
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adhirano.jpg]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>
|-
| Neurofibrillary tangles
| flame-shaped cytoplasmic thingy ~30 micrometers
| aging, Alzheimer's disease
| seen with silver stain
| [http://www.pakmed.net/academic/age/alz/plaques_tanglesBorder.jpg Schematic]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>, [http://faculty.washington.edu/alexbert/MEDEX/Fall/adtangle.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Granulovacuolar degeneration
| cytoplasmic vacuoles 4-5 micrometers
| ageing, [[Alzheimer's disease]], Pick's disease
| main found in Ammon horn<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adgvd.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Pick bodies
| round, homogenous, intracytoplasmic, ~10 micrometers
| [[Pick's disease]]
| pyramidal neurons, dentate granule cells (hippocampus); +ve for tau, tubulin, ubiquitin
| [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?action=view&current=Picks60x.jpg&mediafilter=images]
|-
| Bunina body
| size of Nissl granules, eosinophilic
| [[amyotrophic lateral sclerosis]] (ALS)
| EM: membrane-bound bodies; ubiquitin +ve
| [http://pathol.umin.ac.jp/gakubu/exam/2006jpg/19.jpg]
|-

|}

Image collection: [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?mediafilter=images Inclusion bodies (photobucket.com)].

==Immunohistochemistry==
{{Main|Immunohistochemistry}}
===General===
*S-100.
**Sensitive... but non-specific, e.g. also stains [[melanoma]].

===Glial===
*GFAP (glial fibrillary acidic protein) - should stain perikaryon.

====Glial tumours====
Standard work-up:
*GFAP.
*p53.
*Ki-67.

===Neuronal===
*Synaptophysin.
*Chromogranin.

===Carcinoma vs. glial tumours===
*AE1/AE3 often +ve in glial tumours (e.g. astrocytomas, oligodendrogliomas); CAM5.2 is usu. -ve in glial tumours.<ref name=Ref_PSNP_12>{{Ref PSNP|12}}</ref>

===Others===
*APP (amyloid precursor protein) - detects axonal swellings.
*NF (neurofilament) - detects axonal swellings.

=Brain tumours=
{{main|Neuropathology tumours}}
Tumours are a big part of neuropathology. The most common brain tumour (in adults) is a metastasis. The most common primary tumour (in adults) is glioblastoma which has a horrible prognosis.

=Non-tumour=
==Cerebral hemorrhage==
:See: ''[[Intracranial hematoma]]'' for intracranial bleeds

Includes discussion of:
*[[Epidural hematoma]].
*[[Subdural hematoma]].
*[[Subarachnoid hematoma]].
*[[Intracerebral hematoma]]s.

==Duret hematoma==
*[[AKA]] Duret hemorrhage.
===General===
*Bleed in the upper brainstem (midbrain and pons).
**Thought to be due to transtentorial herniation secondary to supratentorial mass effect (e.g. supratentorial tumour, [[intracranial hemorrhage]]).<ref name=pmid11819006>{{Cite journal | last1 = Parizel | first1 = PM. | last2 = Makkat | first2 = S. | last3 = Jorens | first3 = PG. | last4 = Ozsarlak | first4 = O. | last5 = Cras | first5 = P. | last6 = Van Goethem | first6 = JW. | last7 = van den Hauwe | first7 = L. | last8 = Verlooy | first8 = J. | last9 = De Schepper | first9 = AM. | title = Brainstem hemorrhage in descending transtentorial herniation (Duret hemorrhage). | journal = Intensive Care Med | volume = 28 | issue = 1 | pages = 85-8 | month = Jan | year = 2002 | doi = 10.1007/s00134-001-1160-y | PMID = 11819006 }}</ref>
*Often fatal.<ref name=pmid11098635>{{Cite journal | last1 = Fujimoto | first1 = Y. | last2 = Aguiar | first2 = PH. | last3 = Freitas | first3 = AB. | last4 = de Andrade | first4 = AF. | last5 = Marino Júnior | first5 = R. | title = Recovery from Duret hemorrhage: a rare complication after craniotomy--case report. | journal = Neurol Med Chir (Tokyo) | volume = 40 | issue = 10 | pages = 508-10 | month = Oct | year = 2000 | doi = | PMID = 11098635 }}</ref>
===Gross===
*Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).<ref name=pmid11819006/>

Image:
*[http://library.med.utah.edu/WebPath/jpeg5/CNS037.jpg Duret hemorrhage (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html]. Accessed on: 4 December 2011.</ref>

===Microscopic===
Features:
*RBC extravasation.
*+/-Hemosiderin-laden macrophages.
*+/-Ischemic neurons.

==Alcohol & CNS==
===Clinical===
*Wernicke's encephalopathy
**Mnemonic ''WACO'':
***Wernicke's.
***Ataxia.
***Confusion, confabulation -- Korsakoff.
***Ocular Sx (CN IV palsy).
**Cause: thiamine deficiency.

===Pathology===
Features:<ref>http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract</ref>
*Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex<ref>URL: [http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939 http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939]. Accessed on: 22 September 2010.</ref> usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>
*Central pontine myelinolysis (CPM).<ref name=pmid21085565>{{cite journal |author=Campbell MC |title=Hyponatremia and central pontine myelinolysis as a result of beer potomania: a case report |journal=Prim Care Companion J Clin Psychiatry |volume=12 |issue=4 |pages= |year=2010 |pmid=21085565 |pmc=2983455 |doi=10.4088/PCC.09l00936ecr |url=}}</ref>
**Just what it sound like - myelin loss in the central pons.
**Classically associated with rapid correction of hyponatremia.<ref>{{cite journal |author=Bernsen HJ, Prick MJ |title=Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia |journal=Acta Neurol Belg |volume=99 |issue=3 |pages=189–93 |year=1999 |month=September |pmid=10544728 |doi= |url=}}</ref>
*Mammillary body shrinkage.<ref name=pmid8947329>{{cite journal |author=Shear PK, Sullivan EV, Lane B, Pfefferbaum A |title=Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia |journal=Alcohol. Clin. Exp. Res. |volume=20 |issue=8 |pages=1489-95 |year=1996 |month=November |pmid=8947329 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=1996&volume=20&issue=8&spage=1489}}</ref>
*Anterior cerebellar vermis atrophy; weak finding - as also age-related.<ref name=pmid3478969>{{cite journal |author=Torvik A |title=Brain lesions in alcoholics: neuropathological observations |journal=Acta Med. Scand. Suppl. |volume=717 |issue= |pages=47–54 |year=1987 |pmid=3478969 |doi= |url=}}</ref>
**Vermis atrophy is also seen in schizophrenia.<ref name=pmid1938163>{{cite journal |author=Sandyk R, Kay SR, Merriam AE |title=Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia |journal=Int. J. Neurosci. |volume=57 |issue=3-4 |pages=205–12 |year=1991 |month=April |pmid=1938163 |doi= |url=}}</ref>

====Marchiafava-Bignami Disease====
*Rare.
*Demyelination of the corpus callosum.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>

====Wernicke's encephalopathy====
General:
*Due to thiamine deficiency.
**Malnourishment often accompanies [[alcoholism]].

Features:<ref name=pmid3929155>{{Cite journal | last1 = Torvik | first1 = A. | title = Two types of brain lesions in Wernicke's encephalopathy. | journal = Neuropathol Appl Neurobiol | volume = 11 | issue = 3 | pages = 179-90 | month = | year = | doi = | PMID = 3929155 }}</ref>
*Neurons of mammillary bodies preserved - '''key'''.
*Loss of myelin.
*Hemorrhage.
*Edema.
*Reactive blood vessels.

Note:
*The thalamus and inferior olives show neuronal loss.<ref name=pmid3929155/>

====Common non-specific findings====
*[[Intracranial haemorrhage]] - due to trauma.

==Meningitis==
===General===
*Definition: inflammation of the meninges (pia mater, arachnoid membranes, dura mater).

Classic clinical presentation:
*Neck stiffness.
*Fever.
*+/-Headache.
*+/-Decreased level of consciousness.

CSF findings:
{| class="wikitable sortable"
! Type
! Glucose
! Protein
! Cells
|-
| Bacterial, acute
| low
| high
| neutrophils
|-
| Viral
| normal
| slight elevation
| lymphocytes
|}

====Etiology====
*Infectious.
**Bacterial.
**Viral.
**Parasitic
*Autoimmune.
*Toxic.
*Aseptic - see ''[[Mollaret's meningitis]]''.

Bacterial meningitis - most probably cause by age:<ref>{{Ref PCPBoD8|666-7}}</ref>
{| class="wikitable sortable"
! Age
! Organism
|-
| Neonate
| ''Escherichia coli'', Group B Streptococcus
|-
| Infants, children
| ''Streptococcus pneumoniae''
|-
| Adolescents, young adults
| ''Neisseria meningitidis''
|-
| Elderly
| ''Streptococcus pneumoniae'', ''Listeria monocytogenes''
|}

===Gross===
Features:
*+/-Clouded appearance of the meninges.
*+/-Pus.
*+/-Petechiae.
*+/-Cerebral edema.

====Image====
<gallery>
Image:Streptococcus_pneumoniae_meningitis,_gross_pathology_33_lores.jpg | Meningitis. (WC)
</gallery>

===Microscopic===
Features:
*Inflammation of the meninges:
**+/-[[Neutrophil]]s.
**+/-Lymphocytes.
**+/-[[Plasma cell]]s.
*+/-Microorganisms (infectious meningitis):
**Bacteria.
**[[Fungi]], e.g. [[aspergillosis]] (may be intravascular).

Main DDx:
*[[Lymphoma]].

====Image====
<gallery>
Image:Meningitis_Histopathology.jpg | Bacterial meningitis. (WC)
</gallery>

==Cerebral abscess==
===General===
*May mimic malignancy clinically.

===Microscopic===
Features:
*Sheets of neutrophils surrounded by fibrosing brain.
**Fibrosing brain: pale (lighter pink than normal brain tissue), dense.

Images:
*[http://pathology.class.kmu.edu.tw/ch01/4-1.jpg Cerebral abscess - very low mag. (kmu.edu.tw)].<ref>URL: [http://pathology.class.kmu.edu.tw/ch01/Slide4.htm http://pathology.class.kmu.edu.tw/ch01/Slide4.htm]. Accessed on: 1 January 2012.</ref>
*[http://pathology.class.kmu.edu.tw/ch01/4-5.jpg Cerebral abscess - low mag. (kmu.edu.tw)].

==Neurodegenerative diseases==
{{Main|Neurodegenerative diseases}}
This is a hueueuge topic. It is covered in its own article and includes a general discussion of dementia.

==Epilepsy==
{{Main|Epilepsy}}

==Cerebrovascular accident==
*Abbreviated ''CVA''.
*[[AKA]] ''stroke''.
{{Main|Cerebrovascular accident}}

==Hypoxic-ischemic encephalopathy==
*Abbreviated ''HIE''.
{{Main|Hypoxic-ischemic encephalopathy}}

==Multiple sclerosis==
*Abbreviated ''MS''.
{{Main|Multiple sclerosis}}

==Cerebral amyloid angiopathy==
===General===
*Abbreviated ''CAA''.
*Disease of the old.
*Strong association with ''[[lobar haemorrhage]]'' (bleeds of the cerebellar cortex and cerebral cortex).<ref name=pmid16982664>{{cite journal |author=Thanvi B, Robinson T |title=Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage in older people |journal=Age Ageing |volume=35 |issue=6 |pages=565–71 |year=2006 |month=November |pmid=16982664 |doi=10.1093/ageing/afl108 |url=}}</ref>

Etiology:
*[[Amyloid]] deposition in the basal lamina of smooth muscle (in the cerebellar cortex and cerebral cortex).

===Gross===
*Bleeds typically superficial (cortex and subcortical white matter) and in the frontal lobe or parietal lobe.<ref name=pmid17297004>{{Cite journal | last1 = Haacke | first1 = EM. | last2 = DelProposto | first2 = ZS. | last3 = Chaturvedi | first3 = S. | last4 = Sehgal | first4 = V. | last5 = Tenzer | first5 = M. | last6 = Neelavalli | first6 = J. | last7 = Kido | first7 = D. | title = Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging. | journal = AJNR Am J Neuroradiol | volume = 28 | issue = 2 | pages = 316-7 | month = Feb | year = 2007 | doi = | PMID = 17297004 | URL = http://www.ajnr.org/content/28/2/316.long }}</ref>

===Microscopic===
Features:
*Amorphous, acellular eosinophilic material within walls of small arteries.
**This is a high power diagnosis with congo red staining.

Notes:
*Amyloidosis is seen in all individuals with [[Alzheimer's disease]]; the amount of amyloid is what differs -- in CAA it is lots and lots.
*The white matter is typically spared by CAA.<ref name=pmid19225408>{{Cite journal | last1 = Schröder | first1 = R. | last2 = Deckert | first2 = M. | last3 = Linke | first3 = RP. | title = Novel isolated cerebral ALlambda amyloid angiopathy with widespread subcortical distribution and leukoencephalopathy due to atypical monoclonal plasma cell proliferation, and terminal systemic gammopathy. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 3 | pages = 286-99 | month = Mar | year = 2009 | doi = 10.1097/NEN.0b013e31819a87f9 | PMID = 19225408 }}
</ref>

====Images====
<gallery>
Image:Cerebral_amyloid_angiopathy_-_very_high_mag.jpg |CAA - congo red - very high mag. (WC)
Image:Cerebral_amyloid_angiopathy_-_low_mag.jpg |CAA - congo red - low mag. (WC)
Image:Cerebral_amyloid_angiopathy_-2b-_amyloid_beta_-_high_mag.jpg |CAA - beta-amyloid - high mag. (WC)
</gallery>
===Stains===
*[[Congo red]].

===IHC===
*Abeta-amyloid (AKA beta-amyloid).

==Central pontine myelinolysis==
*Abbreviated ''CPM''.
*[[AKA]] ''pontine myelinolysis''.
===General===
*Classically in the pons, ergo "pontine" is in the name.
*Classically midline, ergo "central" is in the name.
**May occur elsewhere -- known as ''extrapontine myelinolysis''.

Etiology:
*Rapid correction of hyponatremia.<ref name=pmid22080394>{{Cite journal | last1 = Chang | first1 = Y. | last2 = An | first2 = DH. | last3 = Xing | first3 = Y. | last4 = Qi | first4 = X. | title = Central pontine and extrapontine myelinolysis associated with acute hepatic dysfunction. | journal = Neurol Sci | volume = | issue = | pages = | month = Nov | year = 2011 | doi = 10.1007/s10072-011-0838-3 | PMID = 22080394 }}</ref>
*Tacrolimus post-liver transplant.<ref name=pmid21959523>{{Cite journal | last1 = Fukazawa | first1 = K. | last2 = Nishida | first2 = S. | last3 = Aguina | first3 = L. | last4 = Pretto | first4 = E. | title = Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation. | journal = Ann Transplant | volume = 16 | issue = 3 | pages = 139-42 | month = Sep | year = 2011 | doi = | PMID = 21959523 }}</ref>
*Associated with [[alcoholism]] and malnourishment.

Clinical:<ref>{{Cite journal | last1 = Lai | first1 = CC. | last2 = Tan | first2 = CK. | last3 = Lin | first3 = SH. | last4 = Chen | first4 = HW. | title = Central pontine myelinolysis. | journal = CMAJ | volume = 183 | issue = 9 | pages = E605 | month = Jun | year = 2011 | doi = 10.1503/cmaj.090186 | PMID = 21543311 | PMC = 3114939 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114939/?tool=pubmed }}</ref>
*Decreased level of consciousness - most common.
*Quadriplegia.
*Poor prognosis.

===Microscopic===
Features:<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*Myelin loss.
*No inflammation.
*Relative preservation of neurons.

Images:
*[http://neuropathology-web.org/chapter6/images6/6-9l.jpg CPM (neuropathology-web.org)].<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*[http://dartmed.dartmouth.edu/spring09/html/virtual_microscopy_we/ CPM (dartmouth.edu)].

==Vascular malformations==
{{Main|Vascular malformations}}
Types:<ref name=pmid17076525>{{cite journal |author=Prayson RA, Kleinschmidt-DeMasters BK |title=An algorithmic approach to the brain biopsy--part II |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1639–48 |year=2006 |month=November |pmid=17076525 |doi= |url=}}</ref>
#Arteriovenous malformation.
#*Most important clinically - highest risk of bleeding.
#Varix.
#*One large (dilated) vein.
#Venous angioma.
#*Many small veins.
#Cavernous malformation.
#*Vessels are back-to-back (no intervening parenchyma).

Also see: ''[[Sturge-Weber syndrome]]''.

=Cysts=
===General===
*All are "benign", but some may be fatal due to spatial constraints.

===List of cysts===
*[[Colloid cyst]].
**Columnar epithelium.
*Arachnoid cyst - considered precursor of [[meningioma]].
**[[Psammoma bodies]].
**Clumps of cells.
**Whorled pattern.
*[[Dermoid cyst]].
**Skin + adnexal structures.
**... think of ovarian dermoid.
*Epidermoid cyst.
*Choroid plexus cyst.
*Neuroenteric cyst.
**Foregut cyst with connection to dura.<ref>URL: [http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm]. Accessed on: 19 December 2011.</ref>
***Gastrointestinal tract epithelium.
***Usually seen with vertebral anomalies.
*Epithelial cyst.
*Others.

==Colloid cyst==
===General===
Classic presentation:<ref name=pmid15228889>{{Cite journal | last1 = Spears | first1 = RC. | title = Colloid cyst headache. | journal = Curr Pain Headache Rep | volume = 8 | issue = 4 | pages = 297-300 | month = Aug | year = 2004 | doi = | PMID = 15228889 }}</ref>
*Headache - may be relieved by lying down.
*Can cause [[sudden natural death]].<ref name=pmid14716130>{{Cite journal | last1 = Kava | first1 = MP. | last2 = Tullu | first2 = MS. | last3 = Deshmukh | first3 = CT. | last4 = Shenoy | first4 = A. | title = Colloid cyst of the third ventricle: a cause of sudden death in a child. | journal = Indian J Cancer | volume = 40 | issue = 1 | pages = 31-3 | month = | year = | doi = | PMID = 14716130 }}</ref>

===Gross===
*Fluid filled cyst - classically in the third ventricle.

====Images====
<gallery>
Image:Human brain showning a colloid cyst in the third ventricle.jpg| Colloid cyst at autopsy. (Shaktawat ''et al.''<ref name=pmid16867192>{{Cite journal | last1 = Shaktawat | first1 = SS. | last2 = Salman | first2 = WD. | last3 = Twaij | first3 = Z. | last4 = Al-Dawoud | first4 = A. | title = Unexpected death after headache due to a colloid cyst of the third ventricle. | journal = World J Surg Oncol | volume = 4 | issue = | pages = 47 | month = | year = 2006 | doi = 10.1186/1477-7819-4-47 | PMID = 16867192 }}</ref>)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F3.expansion.html Colloid cyst of third ventricle (ajnr.org)].<ref name=pmid11003281/>

===Microscopic===
Features:<ref name=pmid11003281>{{Cite journal | last1 = Armao | first1 = D. | last2 = Castillo | first2 = M. | last3 = Chen | first3 = H. | last4 = Kwock | first4 = L. | title = Colloid cyst of the third ventricle: imaging-pathologic correlation. | journal = AJNR Am J Neuroradiol | volume = 21 | issue = 8 | pages = 1470-7 | month = Sep | year = 2000 | doi = | PMID = 11003281 }}</ref>
*Simple epithelium with ciliated cells and goblet cells.

====Images====
<gallery>
Image:Colloid_Cyst_HE_40x.jpg | Colloid cyst. (WC)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F4.expansion.html Colloid cyst (ajnr.org)].<ref name=pmid11003281/>

=Paediatric pathology=
==Kernicterus==
===General===
*Due to hyperbilirubinemia.<ref name=pmid7063283>{{Cite journal | last1 = Turkel | first1 = SB. | last2 = Miller | first2 = CA. | last3 = Guttenberg | first3 = ME. | last4 = Moynes | first4 = DR. | last5 = Godgman | first5 = JE. | title = A clinical pathologic reappraisal of kernicterus. | journal = Pediatrics | volume = 69 | issue = 3 | pages = 267-72 | month = Mar | year = 1982 | doi = | PMID = 7063283 }}</ref>

===Gross===
*Yellow staining:<ref name=npw>URL: [http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html]. Accessed on: 30 May 2012.</ref>
**Basal ganglia.<ref name=pmid10920171>{{Cite journal | last1 = Hansen | first1 = TW. | last2 = Hervieux | first2 = JF. | last3 = Orth | first3 = J. | last4 = Schmorl | first4 = CG. | last5 = Baumes | first5 = JB. | title = Pioneers in the scientific study of neonatal jaundice and kernicterus. | journal = Pediatrics | volume = 106 | issue = 2 | pages = E15 | month = Aug | year = 2000 | doi = | PMID = 10920171 }}</ref>
**Hippocampus.<ref name=pmid15091133>{{Cite journal | last1 = Paksoy | first1 = Y. | last2 = Koç | first2 = H. | last3 = Genç | first3 = BO. | title = Bilateral mesial temporal sclerosis and kernicterus. | journal = J Comput Assist Tomogr | volume = 28 | issue = 2 | pages = 269-72 | month = | year = | doi = | PMID = 15091133 }}</ref>
**Subthalamic nucleus.

Note:
*May not be specific.<ref name=pmid7063283/>

Image:
*[http://www.flickr.com/photos/neonatal-box/6275988844/ Kernicterus (flickr.com)].

===Microscopic===
Features - similar to [[HIE]]:<ref name=npw/>
*+/-Red neurons.
*+/-Gliosis.

==Joubert syndrome==
*Malformation of the cerebellar vermis.<ref name=ninds_joubert>[http://www.ninds.nih.gov/disorders/joubert/joubert.htm http://www.ninds.nih.gov/disorders/joubert/joubert.htm]</ref>

===Epidemiology===
*Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.<ref name=ninds_joubert/>

=Weird stuff=
==Acute disseminated encephalomyelitis==
*Abbreviated ''ADEM''.
{{Main|Acute disseminated encephalomyelitis}}

==Neuromyelitis optica==
*Abbreviated ''NMO''.
===General===
*Rare autoimmune disease - once considered a variant of [[multiple sclerosis]].
**Autoantibodies directed at aquaporin-4.<ref name=pmid22087205>{{Cite journal | last1 = Kim | first1 = W. | last2 = Kim | first2 = SH. | last3 = Kim | first3 = HJ. | title = New insights into neuromyelitis optica. | journal = J Clin Neurol | volume = 7 | issue = 3 | pages = 115-27 | month = Sep | year = 2011 | doi = 10.3988/jcn.2011.7.3.115 | PMID = 22087205 }}</ref>

Diagnosis:
*NMO-IgG.

Clinical - preferentially:
*Eye (optic neuritis).
*Spinal cord (myelitis).

===Microscopic===
Features:
*Inflammation - lymphocytes, macrophages.
*Reactive astrocytes.

Images:
*[http://path.upmc.edu/cases/case637.html Neuromyelitis optica - several images (upmc.edu)].

===IHC===
*Mixed lymphocyte population with CD3 > CD20.
*Aquaporin-4 loss.

==Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy==
*Commonly abbreviated ''CADASIL''.
{{Main|Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy}}

==Progressive multifocal leukoencephalopathy==
*Abbreviated ''PML''.
{{Main|Progressive multifocal leukoencephalopathy}}

=See also=
*[[Brain tumours]].
*[[Pituitary gland]].
*[[Histiocytoses]].
*[[Intracranial hematomas]].
*[[Spine]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
**[http://www.neuropathologyweb.org/test6/6test.html Quiz (neuropathologyweb.org)].
*[http://blog.lib.umn.edu/santa013/neuropathology/ Neuropathology cases (lib.umn.edu)].
*[http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 Neuropathology micrographs - identifying the site (stonybrookmedicalcenter.org)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/AAQuestion-41-60.htm Neurocytopathology quiz (ouhsc.edu)].
*[http://wiki.cns.org/wiki/index.php/Main_Page WikiCNS (wiki.cns.org)].

[[Category:Neuropathology]]

CNS cytopathology

2015-02-16T18:22:03Z

Ana:

''CNS cytopathology'' is a subset of [[neuropathology]] and [[cytopathology]].

An introduction to cytopathology is in the ''[[cytopathology]]'' article. Cerebrospinal (CSF) specimens are dealt with in a separate article called ''[[CSF cytopathology]]''.
==Technique==
Smears (really squash preps) are common in neuropathology. Here are some tips for getting a good smear:
# Sampling is key -- choose 3-4 small pieces of tissue from different areas of the tissue (if there are different colours, get some of each)
# Keep pieces small (easier to smear)
# Avoid air drying (place into formal alcohol immediately upon smearing)

==Basic approach==
{{familytree/start}}
{{familytree | | | | | | | | | A01 | | | | |A01=CNS cytology}}
{{familytree | | | | |,|-|-|-|-|^|-|-|-|-|.|}}
{{familytree | | | | B01 | | | | | | | | B02|B01=Tumour|B02=Non-tumour }}
{{familytree | |,|-|-|^|-|-|.| | | |,|-|-|^|-|-|.| | |}}
{{familytree | C01 | | | | C02 | | C03 | | | | C04 | |C01=Glial|C02=Non-glial|C03=Infectious|C04=Non-infectious }}
{{familytree/end}}

{| class="wikitable"
|
| Glial
| Non-glial
|-
| Stranding (cytoplasmic)
| thin - cannot be seen at low power (2.5x obj.), true cytoplasmic processes
| thick - can be seen at low power (2.5x obj.), artifact of smearing
|-
| Edge of cluster
| smooth/non-distinct
| sharp
|}

Glial vs non-glial:
*Glial has cytoplasmic processes/cytoplasmic strands (stringy processes) ~ 1 micrometer thick.
**They cannot be seen well at low power.
**Cotton candy-like appearance.
**Images:
*** [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/cf76aad0d9dab70c99b93186ca8b3ad4.gif Stringy processes - glial tumour (msdlatinamerica.com)].<ref name=latinam>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
*** [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/59f74df1106573dcdea73be7febff2aa.gif Glial tumour mimicing a carcinoma (msdlatinamerica.com)].<ref name=latinam>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>

Gliosis vs. neoplasm:
*Gliosis - uniform, pink
*Astrocytoma - irregular, coarse clumps of pink fibrillary material

High grade vs. low-grade:
*Markers of high grade glioma:
# Mitoses (can see these in smear)
# Necrosis (can also see in smears)

Notes:
*Crush artifact (in smear preparation) can mimic glial processes.
**Crush artifact vs. real glial processes:
***No glial processes run perpendicular to the direction of smear.
***Glial processes may branch.
***Crushed/elongated nuclei are present in artifactual processes.


===Meningioma===
Most meningiomas smear rather well, the only exception being ones that are densely fibrous.
*Key features of meningioma smears:
# Single cells or small groups of epithelioid cells with distinct cytoplasmic 'flags' (cytoplasm usually abundant)
# Round nuclei with vesicular chromatin and unapparent or small nucleoli
# Visible actin striations / stress filaments in cells (seen as pink straight lines)

===Metastatic carcinoma===
Typically has a 'cannonball' appearance -- with small, highly cohesive clusters of epithelioid cells.
{{Main|Metastasis}}
*[http://moon.ouhsc.edu/kfung/JTY1/NeuroTest/_derived/Q92-Ans.htm_txt_SampleQ92.gif Squamous cell carcinoma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/JTY1/NeuroTest/Q92-Ans.htm http://moon.ouhsc.edu/kfung/JTY1/NeuroTest/Q92-Ans.htm]. Accessed on: 3 November 2010.</ref>
*[http://moon.ouhsc.edu/kfung/JTY1/NeuroTest/Images/SampleQ50.gif Adenocarcioma (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/JTY1/NeuroTest/Images/SampleQ59.gif Small cell carcinoma (ouhsc.edu)].

==Things that don't smear well==
Cohesive tumours:
*[[Neurofibroma]].
*[[Schwannoma]].<ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>
*Subependymoma
*Abscess (because of fibrous capsule)
*Metastasis.<ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>

===Things that smear well===
Dyscohesive tumours:
*[[Lymphoma]].<ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>
*[[Pituitary adenoma]].<ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>
*Oligodendroglioma.<ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>
*[[Astrocytoma]].
*Normal brain.

==See also==
*[[Neuropathology]].
*[[Neurohistology]].
*[[CNS tumours]].

==References==
{{Reflist|1}}

==External links==
*[http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html Diagnostic neuropathology smears (msdlatinamerica.com)].

[[Category:Cytopathology]]
[[Category:Neuropathology]]

CNS cytopathology

2015-02-16T18:06:36Z

Ana: /* Things that don't smear well */

''CNS cytopathology'' is a subset of [[neuropathology]] and [[cytopathology]].

An introduction to cytopathology is in the ''[[cytopathology]]'' article. Cerebrospinal (CSF) specimens are dealt with in a separate article called ''[[CSF cytopathology]]''.

==Basic approach==
{{familytree/start}}
{{familytree | | | | | | | | | A01 | | | | |A01=CNS cytology}}
{{familytree | | | | |,|-|-|-|-|^|-|-|-|-|.|}}
{{familytree | | | | B01 | | | | | | | | B02|B01=Tumour|B02=Non-tumour }}
{{familytree | |,|-|-|^|-|-|.| | | |,|-|-|^|-|-|.| | |}}
{{familytree | C01 | | | | C02 | | C03 | | | | C04 | |C01=Glial|C02=Non-glial|C03=Infectious|C04=Non-infectious }}
{{familytree/end}}

{| class="wikitable"
|
| Glial
| Non-glial
|-
| Stranding (cytoplasmic)
| thin - cannot be seen at low power (2.5x obj.), true cytoplasmic processes
| thick - can be seen at low power (2.5x obj.), artifact of smearing
|-
| Edge of cluster
| smooth/non-distinct
| sharp
|}

Glial vs non-glial:
*Glial has ctyoplasmic processes/cytoplasmic strands (stringy processes) ~ 1 micrometer thick.
**They cannot be seen well at low power.
**Cotton candy-like appearance.
**Images:
*** [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/cf76aad0d9dab70c99b93186ca8b3ad4.gif Stringy processes - glial tumour (msdlatinamerica.com)].<ref name=latinam>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
*** [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/59f74df1106573dcdea73be7febff2aa.gif Glial tumour mimicing a carcinoma (msdlatinamerica.com)].<ref name=latinam>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>

Notes:
*Crush artifact (in smear preparation) can mimic glial processes.
**Crush artifact vs. real glial processes:
***No glial processes run perpendicular to the direction of smear.
***Glial processes may branch.
***Crushed/elongated nuclei are present in artifactual processes.


===Metastatic carcinoma===
{{Main|Metastasis}}
*[http://moon.ouhsc.edu/kfung/JTY1/NeuroTest/_derived/Q92-Ans.htm_txt_SampleQ92.gif Squamous cell carcinoma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/JTY1/NeuroTest/Q92-Ans.htm http://moon.ouhsc.edu/kfung/JTY1/NeuroTest/Q92-Ans.htm]. Accessed on: 3 November 2010.</ref>
*[http://moon.ouhsc.edu/kfung/JTY1/NeuroTest/Images/SampleQ50.gif Adenocarcioma (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/JTY1/NeuroTest/Images/SampleQ59.gif Small cell carcinoma (ouhsc.edu)].

==Things that don't smear well==
Cohesive tumours:
*[[Meningioma]].<ref name=pmid7962615>{{cite journal |author=Ironside JW |title=Update on central nervous system cytopathology. II. Brain smear technique |journal=J. Clin. Pathol. |volume=47 |issue=8 |pages=683–8 |year=1994 |month=August |pmid=7962615 |pmc=502135 |doi= |url=}}</ref><ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>
*[[Neurofibroma]].<ref name=pmid7962615/>
*[[Schwannoma]].<ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>
*Subependymoma
*Abscess (because of fibrous capsule)
*Metastasis.<ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>

===Things that smear well===
Dyscohesive tumours:
*[[Lymphoma]].<ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>
*[[Pituitary adenoma]].<ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>
*Oligodendroglioma.<ref name=Ref_TPoSP|252>{{Ref TPoSP|252}}</ref>
*[[Astrocytoma]].
*Normal brain.

==See also==
*[[Neuropathology]].
*[[Neurohistology]].
*[[CNS tumours]].

==References==
{{Reflist|1}}

==External links==
*[http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html Diagnostic neuropathology smears (msdlatinamerica.com)].

[[Category:Cytopathology]]
[[Category:Neuropathology]]

Neuropathology

2015-02-16T18:05:23Z

Ana: /* Neuroradiology */

[[Image:MCA-Stroke-Brain-Human-2.JPG|thumb|right|Gross image showing changes of a [[stroke]]. (WC/Marvin 101)]]
This article is an introduction to '''neuropathology'''. There are separate articles for [[brain tumours]], the [[pituitary gland]], the [[spine]], the [[eye]], [[muscle pathologies]], [[neurohistology]] and [[neuroanatomy]].

Neuropathology is the bane of many anatomical pathologists in teaching hospitals... 'cause they have to fill in for the neuropathologist when he or she is on vacation.

==Neuroanatomy==
{{Main|Neuroanatomy}}
This is a large topic. It covered in a separate article, that also covers grossing.

==Neuroradiology==
Key factors to consider in evaluation:
# location
# number of lesions - single vs. multiple
# cystic vs. solid lesion
# enhancement

==Lesion location==
In neuroradiology and neuropathology, real estate is crucial. Lesion location can often narrow your differential.

Cortical lesions (gray matter):
* oligodendroglioma
* DNET
* ganglioglioma
* pleomorphic xanthoastrocytoma
* extraventricular ependymoma

Cortical-subcortical junction:
* metastases
* abscesses (hematogenous spread)

Subcortical lesions (white matter):
* glioblastoma
* diffuse gliomas
* demyelinating plaques

Deep gray matter lesions (e.g. basal ganglia);
* gliomas
* hypertensive hemorrhage

Cerebellar lesions:
* medulloblastoma
* pilocytic astrocytoma
* AT/RT

Intraventricular lesions:
* ependymoma
* subependymoma
* pilocytic astrocytoma
* central neurocytoma
* rosette forming glioneuronal tumour of the fourth ventricle

Suprasellar (above the pituitary):
* craniopharyngioma
* germinoma
* pilomyxoid astrocytoma

==Number of lesions==
If ''single'' lesion = think primary, neoplastic
If ''multiple'' lesions = think metastatic, neoplastic or infectious
'''NB: glioblastoma can be multifocal''' (and the foci can be quite far apart)

==Cystic vs. solid lesions==
Some tumours are classically cystic with a small solid component (so-called cyst with a mural nodule) -- e.g. pilocytic astrocytoma, ganglioglioma, hemangioblastoma

==Enhancing vs. non-enhancing:==
*In adults, enhancing generally = high grade.
*In pediatrics, it often depends on the pattern.
Two main patterns to be mindful of -- ring enhancing lesions, and cystic lesions with a mural nodule.

===Ring enhancing lesions===
In [[HIV]]/AIDS patients... mass on CT if infection:
*[[Toxoplasmosis]] - most common.<ref>MUN. Feb 3, 2009.</ref>

Ring enhancing lesion (DDx) - mnemonic ''MAGICAL DR'':<ref>{{Ref TN2005 |NS7}}</ref>
*Metstasis.
*Abscess.
*[[Glioblastoma]].
*[[Infarct]].
*Contusion.
*AIDS-related.
*[[Lymphoma]] + [[HIV]] assoc. disease (toxoplasma).
*Demyelination (e.g. [[multiple sclerosis]]).
*Resolving hematoma.

===Cyst with enhancing mural nodule===
*hemangioblastoma (#1 in adults)
*pilocytic astrocytoma (#1 in peds)
*pleomorphic xanthoastrocytoma
*ganglioglioma

==Grossing==
This is covered in the ''[[neuroanatomy]]'' article.

===Gross pathology===
The gross usually useless for arriving at a definitive diagnosis.

Exceptions:<ref>R. Kiehl. 8 November 2010.</ref>
*Sausage shape lesion of filum terminale = [[myxopapillary ependymoma]].
*Soft & tan colour = [[pituitary adenoma]].

==Normal histology==
{{main|Neurohistology}}
This is a big topic. It is covered in a separate article called ''[[neurohistology]]''.

==Histopathology==
===Neuronal changes===
====Anoxic neurons====
*[[AKA]] ''red neurons''.

Features:
*Intensely red cytoplasm.
*Pyknosis = nuclear shrinkage + darker staining.

=====Images=====
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons (WC)
Image:AcuteStroke_HE400x.jpg | Neurons in an acute stroke. (WC)
</gallery>
www:
*[http://neuropathology-web.org/chapter2/images2/2-anoxic.png Anoxic neurons (neuropathologyweb.org)].<ref>URL: [http://neuropathology-web.org/chapter2/chapter2aHIE.html http://neuropathology-web.org/chapter2/chapter2aHIE.html]. Accessed on: 10 December 2014.</ref>
*[http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-16.gif Anoxic neurons (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>

====Central chromatolysis====
Features:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html]. Accessed on: 22 December 2010.</ref>
*Central clearing.
**Nucleus and Nissl substance are pushed to cell periphery.

DDx:
*Axonal injury (traumatic).<ref name=pmid8909880>{{cite journal |author=Holland GR |title=Experimental trigeminal nerve injury |journal=Crit. Rev. Oral Biol. Med. |volume=7 |issue=3 |pages=237–58 |year=1996 |pmid=8909880 |doi= |url=}}</ref>
*Vitamin deficiency ([[pellagra]]).<ref name=pmid15577526>{{cite journal |author=Piercecchi-Marti MD, Pélissier-Alicot AL, Leonetti G, Tervé JP, Cianfarani F, Pellissier JF |title=Pellagra: a rare disease observed in a victim of mental and physical abuse |journal=Am J Forensic Med Pathol |volume=25 |issue=4 |pages=342–4 |year=2004 |month=December |pmid=15577526 |doi= |url=}}</ref>

=====Images=====
<gallery>
Image:Central_chromatolysis_-_intermed_mag_-_cropped.jpg | Central chromatolysis - intermed. mag. (WC)
Image:Central_chromatolysis_-_nf_-_very_high_mag.jpg | Central chromatolysis - NF stain - very high mag. (WC)
</gallery>
====Axonal swellings====
H&E:
*Eosinophilic (light pink) - ground glass-like appearance.
*Shape:
**Round if sectioned perpendicular to axis of axon.
***Bound by cell membrane.
***Large ~ typically 2-4x RBC diameter.
**Sausage-shaped if cut in along axis.

Images:
*[http://frontalcortex.com/gallery/pics/gliageek_VWMDx200.jpg Axonal swelling (frontalcortex.com)].<ref>URL: [http://frontalcortex.com/?page=oll&topic=24&qid=602 http://frontalcortex.com/?page=oll&topic=24&qid=602]. Accessed on: 3 November 2010.</ref>
*[http://www.neuropathologyweb.org/chapter3/images3/3-pvlaxonsweling.jpg Axonal swelling (neuropathologyweb.org)].

=====IHC=====
*APP.

Image:
*[http://vet.sagepub.com/content/37/6/677/F7.expansion.html Axonal swelling - APP (sagepub.com)].<ref>{{cite journal |author=Finnie JW, Manavis J, Blumbergs PC, Kuchel TR |title=Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin |journal=Vet. Pathol. |volume=37 |issue=6 |pages=677–80 |year=2000 |month=November |pmid=11105962 |doi= |url=http://vet.sagepub.com/content/37/6/677.full}}</ref>

===Glial changes===
====Astrocyte changes====
Reactive astrocytes:
*Approximately equally-spaced; distance between neighbouring astrocytes is ~2x (or more) the cell size.
*Well-defined cell border.
*Eosinophilic cytoplasm with many branching processes.
**Classically described as "funnel-shaped" in benign astrocytes.<ref>MUN. 15 November 2010.</ref>
*Peripheral nucleus.
<gallery>
Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg | Reactive astrocytes - high mag. (WC)
</gallery>

Alzheimer type II astrocyte:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 2 July 2010.</ref>
*Large cleared nucleus - '''key feature'''.
*Indistinct cytoplasm.
*Found in the context of ''hepatic encephalopathy'' in basal ganglia and lower layers of cortex.<ref name=Ref_Klatt202>{{Ref Klatt|202}}</ref>
*Images:
**[http://neuroquiz.com/?page=image&topic=1&qid=2714 Alzheimer type II astrocytes (neuroquiz.com)].
**[http://www.neuropathologyweb.org/chapter10/images10/10-AlzIIl.jpg Alzheimer type II astrocytes (neuropathologyweb.org)] .
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag.jpg| Alzheimer type II astrocytes. (WC)
</gallery>

Creutzfeldt cell:<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
*Finding associated with demyelinating disease.
*Image: [http://path.upmc.edu/cases/case336/images/fig03.jpg Crutzfeldt cell (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case336.html http://path.upmc.edu/cases/case336.html]. Accessed on: 15 January 2012.</ref>

Gemistocytic astrocytes:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 7 November 2010.</ref>
*Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:<ref name=Ref_MBNP173>{{Ref MBNP|173}}</ref>
*Cellular processes loaded with tau protein (as may be seen with tau [[IHC]] or Gallyas silver stain); Parisian-star-like appearance with special stain.
*+/-Multinucleated.
*A classic feature of ''[[progressive supranuclear palsy]]''.

====Other glial====
Bergmann gliosis (in the cerebellum):<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Thin layer of cells (2-3 cells) with open nuclei that are larger than granular cell layer nuclei; seen with Purkinje cell loss.

<gallery>
Image:Bergmann_gliosis_-_intermed_mag.jpg | Bergmann gliosis - intermed. mag. (WC)
Image:Bergmann_gliosis_-_high_mag.jpg | Bergmann gliosis - high mag. (WC)
Image:Metastatic_adenocarcinoma_-_cerebellum_-_intermed_mag.jpg | Bergmann gliosis due to compression by metastasis - intermed mag. (WC)
</gallery>
Image:
*[http://tpx.sagepub.com/content/35/5/676/F5.expansion.html Bergmann gliosis (sagepub.com)].

====Reactive change vs. malignancy====
Reactive changes vs. malignancy (mnemonic ''MIMICS''):<ref name=Ref_TPoSP254>{{Ref TPoSP|254}}</ref>
*'''MI'''crovesicular pattern.
*'''M'''itoses.
*'''I'''rregular spacing.
*'''C'''alcifications.
*'''S'''atellitosis, perineuronal.
**Large "crowds" of glial cells associated with nuclei.

===Inflammatory===
DDx:
*Autoimmune - [[Multiple sclerosis]].
*Neoplastic - [[Neuropathology tumours#CNS lymphoma|CNS lymphoma]].
*Infectious - [[HSV]].

====Encephalitis====
=====General=====
DDx:
*Viral encephalitis.
*Paraneoplastic syndromes.

=====Gross=====
*Frontal and temporal lobe - most common for HSV encephalitis.<ref>{{Ref APBR|416 Q47}}</ref>

=====Microscopic=====
Features:<ref name=pmid20051019>{{Cite journal | last1 = Takei | first1 = H. | last2 = Wilfong | first2 = A. | last3 = Malphrus | first3 = A. | last4 = Yoshor | first4 = D. | last5 = Hunter | first5 = JV. | last6 = Armstrong | first6 = DL. | last7 = Bhattacharjee | first7 = MB. | title = Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of the literature. | journal = Neuropathology | volume = 30 | issue = 4 | pages = 381-91 | month = Aug | year = 2010 | doi = 10.1111/j.1440-1789.2009.01079.x | PMID = 20051019 }}</ref>
*Perivascular inflammation.
*Microglia.
*+/-Neuronophagia.
**Phagocytosis of neurons.<ref>URL: [http://medical-dictionary.thefreedictionary.com/neuronophagia http://medical-dictionary.thefreedictionary.com/neuronophagia]. Accessed on: 11 April 2012.</ref>
*+/-Viral cytopathic changes.
*+/-Perineuronal inflammation.

Notes:
*Hemorrhage<ref name=pmid18246335>{{Cite journal | last1 = Vossough | first1 = A. | last2 = Zimmerman | first2 = RA. | last3 = Bilaniuk | first3 = LT. | last4 = Schwartz | first4 = EM. | title = Imaging findings of neonatal herpes simplex virus type 2 encephalitis. | journal = Neuroradiology | volume = 50 | issue = 4 | pages = 355-66 | month = Apr | year = 2008 | doi = 10.1007/s00234-007-0349-3 | PMID = 18246335 }}</ref> and necrosis - characteristic of HSV encephalitis.

Image:
*[http://neuropathology-web.org/chapter5/images5/5-21l.jpg HSV encephalitis (neuropathology-web.org)].<ref>URL: [http://neuropathology-web.org/chapter5/chapter5dViruses.html http://neuropathology-web.org/chapter5/chapter5dViruses.html]. Accessed on: 27 January 2012.</ref>

=====IHC=====
IHC stains for:
*Viral etiologies, e.g. [[HSV]], [[CMV]].
*Parasites, e.g. [[toxoplasma]].
*[[Fungi]], e.g. PASD.

===Architecture===
====Rosettes====
*Rosette = circular/flower-like arrangement of cells.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>

*Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**[[Ependymoma]].
**[[Medulloblastoma]], PNET.
**[[Central neurocytoma]].
**[[Glioblastoma]]s.

*Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**Medulloblastoma.
***Image: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Images/N1-TU-01-17.gif Medulloblastoma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17 http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17]. Accessed on: 3 December 2010.</ref>
**PNET (can be thought of as a supratentorial medulloblastoma) .

*Flexner-Wintersteiner rosette = rosette with empty centre (donut hole).<ref name=pmid16551982/>
**[[Retinoblastoma]]s.
**Pineoblastomas.
**Medulloepitheliomas.

*True ependymal rosette = surrounds a space.<ref name=pmid16551982/>
**[[Ependymoma]].

*Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**Similar to Homer-Wright rosette.
**[[Pineocytoma]].
**[[Neurocytoma]].

====Other====
*Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
**Key feature: variable thickness; helps separate from RBCs.
**Well-seen on trichrome stains.
<gallery>
Image:Rosenthal_HE_40x.jpg | Rosenthal fibres. (WP)
Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear (WC/AFIP)
</gallery>
*Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.<ref>{{Ref MBNP|11}}</ref>
**Image: [Image:Pilocytic_Micro.jpg EGBs (WC/AFIP)].
*Pseudopalisading - picket fence-like alignment of cells; long axis of cells perpendicular to interface with other structures/cells.
**Pseudopalisading of tumour cells (around necrotic regions) is seen in [[glioblastoma]].

Note:
*Good set of articles: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=Neuropathology%20for%20the%20neuroradiologist Neuropathology for radiologists (ncbi.nlm.nih.gov)].

===Inclusion bodies===
*Negri bodies.
**Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
**[[Rabies]].
<gallery>
Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg | Negri bodies. (WC/CDC)
</gallery>

*Lewy bodies.
**Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.<ref name=pmid15235805>{{cite journal |author=Marui W, Iseki E, Kato M, Akatsu H, Kosaka K |title=Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease |journal=Acta Neuropathol. |volume=108 |issue=2 |pages=121–8 |year=2004 |month=August |pmid=15235805 |doi=10.1007/s00401-004-0869-4 |url=}}</ref>
<gallery>
Image:Lewy_Koerperchen.JPG | Lewy body. (WC)
</gallery>
====Table of inclusions====
{| class="wikitable sortable"
! Feature
! Appearance
! Associated disease
! Comment
! Image
|-
| Grumous bodies [[AKA]] granular bodies
| granular and eosinophilic ~50 micrometers
| neurodegenerative disease, neuroaxonal dystrophies, aging
| ?Comment
| ?Image
|-
| Cowdry type 1 AKA Cowdry type A
| eosinophilic & round + halo
| [[herpes simplex virus]]
| can be confused with Lewy body, Marinesco body
| ?Image
|-
| Lewy body
| round cytoplasmic eosinophilic body +/- pale halo
| [[Parkinson disease]], dementia with Lewy bodies
| morphology dependent on location in brain; +ve for alpha-synuclein, alpha-B crystallin, ubiquitin
| [[Image:Lewy_Koerperchen.JPG |thumb|center|150px|]], [http://firstaidteam.com/usmlerximages/v/USMLERxLewy+bodies.gif.html]
|-
| Lafora body
| round
| myoclonic [[epilepsy]]
| look like corpora amylacea; location: dentate nucleus, liver, skeletal muscle, sweat glands
| ?Image
|-
| Lipofuscin
| yellow & granular
| aging
| olive, dendate
| ?Image
|-
| Negri body
| small eosinophic bodies
| rabies
| found in hippocampal neurons and Purkinje cells
| [[Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg|thumb|center|150px|]]
|-
| Hirano body
| concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron
| Alzheimer disease, Pick disease<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| actin crystals, may look like capillaries; location: CA1 of hippocampus
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adhirano.jpg]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>
|-
| Neurofibrillary tangles
| flame-shaped cytoplasmic thingy ~30 micrometers
| aging, Alzheimer's disease
| seen with silver stain
| [http://www.pakmed.net/academic/age/alz/plaques_tanglesBorder.jpg Schematic]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>, [http://faculty.washington.edu/alexbert/MEDEX/Fall/adtangle.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Granulovacuolar degeneration
| cytoplasmic vacuoles 4-5 micrometers
| ageing, [[Alzheimer's disease]], Pick's disease
| main found in Ammon horn<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adgvd.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Pick bodies
| round, homogenous, intracytoplasmic, ~10 micrometers
| [[Pick's disease]]
| pyramidal neurons, dentate granule cells (hippocampus); +ve for tau, tubulin, ubiquitin
| [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?action=view&current=Picks60x.jpg&mediafilter=images]
|-
| Bunina body
| size of Nissl granules, eosinophilic
| [[amyotrophic lateral sclerosis]] (ALS)
| EM: membrane-bound bodies; ubiquitin +ve
| [http://pathol.umin.ac.jp/gakubu/exam/2006jpg/19.jpg]
|-

|}

Image collection: [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?mediafilter=images Inclusion bodies (photobucket.com)].

==Immunohistochemistry==
{{Main|Immunohistochemistry}}
===General===
*S-100.
**Sensitive... but non-specific, e.g. also stains [[melanoma]].

===Glial===
*GFAP (glial fibrillary acidic protein) - should stain perikaryon.

====Glial tumours====
Standard work-up:
*GFAP.
*p53.
*Ki-67.

===Neuronal===
*Synaptophysin.
*Chromogranin.

===Carcinoma vs. glial tumours===
*AE1/AE3 often +ve in glial tumours (e.g. astrocytomas, oligodendrogliomas); CAM5.2 is usu. -ve in glial tumours.<ref name=Ref_PSNP_12>{{Ref PSNP|12}}</ref>

===Others===
*APP (amyloid precursor protein) - detects axonal swellings.
*NF (neurofilament) - detects axonal swellings.

=Brain tumours=
{{main|Neuropathology tumours}}
Tumours are a big part of neuropathology. The most common brain tumour (in adults) is a metastasis. The most common primary tumour (in adults) is glioblastoma which has a horrible prognosis.

=Non-tumour=
==Cerebral hemorrhage==
:See: ''[[Intracranial hematoma]]'' for intracranial bleeds

Includes discussion of:
*[[Epidural hematoma]].
*[[Subdural hematoma]].
*[[Subarachnoid hematoma]].
*[[Intracerebral hematoma]]s.

==Duret hematoma==
*[[AKA]] Duret hemorrhage.
===General===
*Bleed in the upper brainstem (midbrain and pons).
**Thought to be due to transtentorial herniation secondary to supratentorial mass effect (e.g. supratentorial tumour, [[intracranial hemorrhage]]).<ref name=pmid11819006>{{Cite journal | last1 = Parizel | first1 = PM. | last2 = Makkat | first2 = S. | last3 = Jorens | first3 = PG. | last4 = Ozsarlak | first4 = O. | last5 = Cras | first5 = P. | last6 = Van Goethem | first6 = JW. | last7 = van den Hauwe | first7 = L. | last8 = Verlooy | first8 = J. | last9 = De Schepper | first9 = AM. | title = Brainstem hemorrhage in descending transtentorial herniation (Duret hemorrhage). | journal = Intensive Care Med | volume = 28 | issue = 1 | pages = 85-8 | month = Jan | year = 2002 | doi = 10.1007/s00134-001-1160-y | PMID = 11819006 }}</ref>
*Often fatal.<ref name=pmid11098635>{{Cite journal | last1 = Fujimoto | first1 = Y. | last2 = Aguiar | first2 = PH. | last3 = Freitas | first3 = AB. | last4 = de Andrade | first4 = AF. | last5 = Marino Júnior | first5 = R. | title = Recovery from Duret hemorrhage: a rare complication after craniotomy--case report. | journal = Neurol Med Chir (Tokyo) | volume = 40 | issue = 10 | pages = 508-10 | month = Oct | year = 2000 | doi = | PMID = 11098635 }}</ref>
===Gross===
*Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).<ref name=pmid11819006/>

Image:
*[http://library.med.utah.edu/WebPath/jpeg5/CNS037.jpg Duret hemorrhage (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html]. Accessed on: 4 December 2011.</ref>

===Microscopic===
Features:
*RBC extravasation.
*+/-Hemosiderin-laden macrophages.
*+/-Ischemic neurons.

==Alcohol & CNS==
===Clinical===
*Wernicke's encephalopathy
**Mnemonic ''WACO'':
***Wernicke's.
***Ataxia.
***Confusion, confabulation -- Korsakoff.
***Ocular Sx (CN IV palsy).
**Cause: thiamine deficiency.

===Pathology===
Features:<ref>http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract</ref>
*Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex<ref>URL: [http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939 http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939]. Accessed on: 22 September 2010.</ref> usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>
*Central pontine myelinolysis (CPM).<ref name=pmid21085565>{{cite journal |author=Campbell MC |title=Hyponatremia and central pontine myelinolysis as a result of beer potomania: a case report |journal=Prim Care Companion J Clin Psychiatry |volume=12 |issue=4 |pages= |year=2010 |pmid=21085565 |pmc=2983455 |doi=10.4088/PCC.09l00936ecr |url=}}</ref>
**Just what it sound like - myelin loss in the central pons.
**Classically associated with rapid correction of hyponatremia.<ref>{{cite journal |author=Bernsen HJ, Prick MJ |title=Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia |journal=Acta Neurol Belg |volume=99 |issue=3 |pages=189–93 |year=1999 |month=September |pmid=10544728 |doi= |url=}}</ref>
*Mammillary body shrinkage.<ref name=pmid8947329>{{cite journal |author=Shear PK, Sullivan EV, Lane B, Pfefferbaum A |title=Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia |journal=Alcohol. Clin. Exp. Res. |volume=20 |issue=8 |pages=1489-95 |year=1996 |month=November |pmid=8947329 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=1996&volume=20&issue=8&spage=1489}}</ref>
*Anterior cerebellar vermis atrophy; weak finding - as also age-related.<ref name=pmid3478969>{{cite journal |author=Torvik A |title=Brain lesions in alcoholics: neuropathological observations |journal=Acta Med. Scand. Suppl. |volume=717 |issue= |pages=47–54 |year=1987 |pmid=3478969 |doi= |url=}}</ref>
**Vermis atrophy is also seen in schizophrenia.<ref name=pmid1938163>{{cite journal |author=Sandyk R, Kay SR, Merriam AE |title=Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia |journal=Int. J. Neurosci. |volume=57 |issue=3-4 |pages=205–12 |year=1991 |month=April |pmid=1938163 |doi= |url=}}</ref>

====Marchiafava-Bignami Disease====
*Rare.
*Demyelination of the corpus callosum.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>

====Wernicke's encephalopathy====
General:
*Due to thiamine deficiency.
**Malnourishment often accompanies [[alcoholism]].

Features:<ref name=pmid3929155>{{Cite journal | last1 = Torvik | first1 = A. | title = Two types of brain lesions in Wernicke's encephalopathy. | journal = Neuropathol Appl Neurobiol | volume = 11 | issue = 3 | pages = 179-90 | month = | year = | doi = | PMID = 3929155 }}</ref>
*Neurons of mammillary bodies preserved - '''key'''.
*Loss of myelin.
*Hemorrhage.
*Edema.
*Reactive blood vessels.

Note:
*The thalamus and inferior olives show neuronal loss.<ref name=pmid3929155/>

====Common non-specific findings====
*[[Intracranial haemorrhage]] - due to trauma.

==Meningitis==
===General===
*Definition: inflammation of the meninges (pia mater, arachnoid membranes, dura mater).

Classic clinical presentation:
*Neck stiffness.
*Fever.
*+/-Headache.
*+/-Decreased level of consciousness.

CSF findings:
{| class="wikitable sortable"
! Type
! Glucose
! Protein
! Cells
|-
| Bacterial, acute
| low
| high
| neutrophils
|-
| Viral
| normal
| slight elevation
| lymphocytes
|}

====Etiology====
*Infectious.
**Bacterial.
**Viral.
**Parasitic
*Autoimmune.
*Toxic.
*Aseptic - see ''[[Mollaret's meningitis]]''.

Bacterial meningitis - most probably cause by age:<ref>{{Ref PCPBoD8|666-7}}</ref>
{| class="wikitable sortable"
! Age
! Organism
|-
| Neonate
| ''Escherichia coli'', Group B Streptococcus
|-
| Infants, children
| ''Streptococcus pneumoniae''
|-
| Adolescents, young adults
| ''Neisseria meningitidis''
|-
| Elderly
| ''Streptococcus pneumoniae'', ''Listeria monocytogenes''
|}

===Gross===
Features:
*+/-Clouded appearance of the meninges.
*+/-Pus.
*+/-Petechiae.
*+/-Cerebral edema.

====Image====
<gallery>
Image:Streptococcus_pneumoniae_meningitis,_gross_pathology_33_lores.jpg | Meningitis. (WC)
</gallery>

===Microscopic===
Features:
*Inflammation of the meninges:
**+/-[[Neutrophil]]s.
**+/-Lymphocytes.
**+/-[[Plasma cell]]s.
*+/-Microorganisms (infectious meningitis):
**Bacteria.
**[[Fungi]], e.g. [[aspergillosis]] (may be intravascular).

Main DDx:
*[[Lymphoma]].

====Image====
<gallery>
Image:Meningitis_Histopathology.jpg | Bacterial meningitis. (WC)
</gallery>

==Cerebral abscess==
===General===
*May mimic malignancy clinically.

===Microscopic===
Features:
*Sheets of neutrophils surrounded by fibrosing brain.
**Fibrosing brain: pale (lighter pink than normal brain tissue), dense.

Images:
*[http://pathology.class.kmu.edu.tw/ch01/4-1.jpg Cerebral abscess - very low mag. (kmu.edu.tw)].<ref>URL: [http://pathology.class.kmu.edu.tw/ch01/Slide4.htm http://pathology.class.kmu.edu.tw/ch01/Slide4.htm]. Accessed on: 1 January 2012.</ref>
*[http://pathology.class.kmu.edu.tw/ch01/4-5.jpg Cerebral abscess - low mag. (kmu.edu.tw)].

==Neurodegenerative diseases==
{{Main|Neurodegenerative diseases}}
This is a hueueuge topic. It is covered in its own article and includes a general discussion of dementia.

==Epilepsy==
{{Main|Epilepsy}}

==Cerebrovascular accident==
*Abbreviated ''CVA''.
*[[AKA]] ''stroke''.
{{Main|Cerebrovascular accident}}

==Hypoxic-ischemic encephalopathy==
*Abbreviated ''HIE''.
{{Main|Hypoxic-ischemic encephalopathy}}

==Multiple sclerosis==
*Abbreviated ''MS''.
{{Main|Multiple sclerosis}}

==Cerebral amyloid angiopathy==
===General===
*Abbreviated ''CAA''.
*Disease of the old.
*Strong association with ''[[lobar haemorrhage]]'' (bleeds of the cerebellar cortex and cerebral cortex).<ref name=pmid16982664>{{cite journal |author=Thanvi B, Robinson T |title=Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage in older people |journal=Age Ageing |volume=35 |issue=6 |pages=565–71 |year=2006 |month=November |pmid=16982664 |doi=10.1093/ageing/afl108 |url=}}</ref>

Etiology:
*[[Amyloid]] deposition in the basal lamina of smooth muscle (in the cerebellar cortex and cerebral cortex).

===Gross===
*Bleeds typically superficial (cortex and subcortical white matter) and in the frontal lobe or parietal lobe.<ref name=pmid17297004>{{Cite journal | last1 = Haacke | first1 = EM. | last2 = DelProposto | first2 = ZS. | last3 = Chaturvedi | first3 = S. | last4 = Sehgal | first4 = V. | last5 = Tenzer | first5 = M. | last6 = Neelavalli | first6 = J. | last7 = Kido | first7 = D. | title = Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging. | journal = AJNR Am J Neuroradiol | volume = 28 | issue = 2 | pages = 316-7 | month = Feb | year = 2007 | doi = | PMID = 17297004 | URL = http://www.ajnr.org/content/28/2/316.long }}</ref>

===Microscopic===
Features:
*Amorphous, acellular eosinophilic material within walls of small arteries.
**This is a high power diagnosis with congo red staining.

Notes:
*Amyloidosis is seen in all individuals with [[Alzheimer's disease]]; the amount of amyloid is what differs -- in CAA it is lots and lots.
*The white matter is typically spared by CAA.<ref name=pmid19225408>{{Cite journal | last1 = Schröder | first1 = R. | last2 = Deckert | first2 = M. | last3 = Linke | first3 = RP. | title = Novel isolated cerebral ALlambda amyloid angiopathy with widespread subcortical distribution and leukoencephalopathy due to atypical monoclonal plasma cell proliferation, and terminal systemic gammopathy. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 3 | pages = 286-99 | month = Mar | year = 2009 | doi = 10.1097/NEN.0b013e31819a87f9 | PMID = 19225408 }}
</ref>

====Images====
<gallery>
Image:Cerebral_amyloid_angiopathy_-_very_high_mag.jpg |CAA - congo red - very high mag. (WC)
Image:Cerebral_amyloid_angiopathy_-_low_mag.jpg |CAA - congo red - low mag. (WC)
Image:Cerebral_amyloid_angiopathy_-2b-_amyloid_beta_-_high_mag.jpg |CAA - beta-amyloid - high mag. (WC)
</gallery>
===Stains===
*[[Congo red]].

===IHC===
*Abeta-amyloid (AKA beta-amyloid).

==Central pontine myelinolysis==
*Abbreviated ''CPM''.
*[[AKA]] ''pontine myelinolysis''.
===General===
*Classically in the pons, ergo "pontine" is in the name.
*Classically midline, ergo "central" is in the name.
**May occur elsewhere -- known as ''extrapontine myelinolysis''.

Etiology:
*Rapid correction of hyponatremia.<ref name=pmid22080394>{{Cite journal | last1 = Chang | first1 = Y. | last2 = An | first2 = DH. | last3 = Xing | first3 = Y. | last4 = Qi | first4 = X. | title = Central pontine and extrapontine myelinolysis associated with acute hepatic dysfunction. | journal = Neurol Sci | volume = | issue = | pages = | month = Nov | year = 2011 | doi = 10.1007/s10072-011-0838-3 | PMID = 22080394 }}</ref>
*Tacrolimus post-liver transplant.<ref name=pmid21959523>{{Cite journal | last1 = Fukazawa | first1 = K. | last2 = Nishida | first2 = S. | last3 = Aguina | first3 = L. | last4 = Pretto | first4 = E. | title = Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation. | journal = Ann Transplant | volume = 16 | issue = 3 | pages = 139-42 | month = Sep | year = 2011 | doi = | PMID = 21959523 }}</ref>
*Associated with [[alcoholism]] and malnourishment.

Clinical:<ref>{{Cite journal | last1 = Lai | first1 = CC. | last2 = Tan | first2 = CK. | last3 = Lin | first3 = SH. | last4 = Chen | first4 = HW. | title = Central pontine myelinolysis. | journal = CMAJ | volume = 183 | issue = 9 | pages = E605 | month = Jun | year = 2011 | doi = 10.1503/cmaj.090186 | PMID = 21543311 | PMC = 3114939 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114939/?tool=pubmed }}</ref>
*Decreased level of consciousness - most common.
*Quadriplegia.
*Poor prognosis.

===Microscopic===
Features:<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*Myelin loss.
*No inflammation.
*Relative preservation of neurons.

Images:
*[http://neuropathology-web.org/chapter6/images6/6-9l.jpg CPM (neuropathology-web.org)].<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*[http://dartmed.dartmouth.edu/spring09/html/virtual_microscopy_we/ CPM (dartmouth.edu)].

==Vascular malformations==
{{Main|Vascular malformations}}
Types:<ref name=pmid17076525>{{cite journal |author=Prayson RA, Kleinschmidt-DeMasters BK |title=An algorithmic approach to the brain biopsy--part II |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1639–48 |year=2006 |month=November |pmid=17076525 |doi= |url=}}</ref>
#Arteriovenous malformation.
#*Most important clinically - highest risk of bleeding.
#Varix.
#*One large (dilated) vein.
#Venous angioma.
#*Many small veins.
#Cavernous malformation.
#*Vessels are back-to-back (no intervening parenchyma).

Also see: ''[[Sturge-Weber syndrome]]''.

=Cysts=
===General===
*All are "benign", but some may be fatal due to spatial constraints.

===List of cysts===
*[[Colloid cyst]].
**Columnar epithelium.
*Arachnoid cyst - considered precursor of [[meningioma]].
**[[Psammoma bodies]].
**Clumps of cells.
**Whorled pattern.
*[[Dermoid cyst]].
**Skin + adnexal structures.
**... think of ovarian dermoid.
*Epidermoid cyst.
*Choroid plexus cyst.
*Neuroenteric cyst.
**Foregut cyst with connection to dura.<ref>URL: [http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm]. Accessed on: 19 December 2011.</ref>
***Gastrointestinal tract epithelium.
***Usually seen with vertebral anomalies.
*Epithelial cyst.
*Others.

==Colloid cyst==
===General===
Classic presentation:<ref name=pmid15228889>{{Cite journal | last1 = Spears | first1 = RC. | title = Colloid cyst headache. | journal = Curr Pain Headache Rep | volume = 8 | issue = 4 | pages = 297-300 | month = Aug | year = 2004 | doi = | PMID = 15228889 }}</ref>
*Headache - may be relieved by lying down.
*Can cause [[sudden natural death]].<ref name=pmid14716130>{{Cite journal | last1 = Kava | first1 = MP. | last2 = Tullu | first2 = MS. | last3 = Deshmukh | first3 = CT. | last4 = Shenoy | first4 = A. | title = Colloid cyst of the third ventricle: a cause of sudden death in a child. | journal = Indian J Cancer | volume = 40 | issue = 1 | pages = 31-3 | month = | year = | doi = | PMID = 14716130 }}</ref>

===Gross===
*Fluid filled cyst - classically in the third ventricle.

====Images====
<gallery>
Image:Human brain showning a colloid cyst in the third ventricle.jpg| Colloid cyst at autopsy. (Shaktawat ''et al.''<ref name=pmid16867192>{{Cite journal | last1 = Shaktawat | first1 = SS. | last2 = Salman | first2 = WD. | last3 = Twaij | first3 = Z. | last4 = Al-Dawoud | first4 = A. | title = Unexpected death after headache due to a colloid cyst of the third ventricle. | journal = World J Surg Oncol | volume = 4 | issue = | pages = 47 | month = | year = 2006 | doi = 10.1186/1477-7819-4-47 | PMID = 16867192 }}</ref>)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F3.expansion.html Colloid cyst of third ventricle (ajnr.org)].<ref name=pmid11003281/>

===Microscopic===
Features:<ref name=pmid11003281>{{Cite journal | last1 = Armao | first1 = D. | last2 = Castillo | first2 = M. | last3 = Chen | first3 = H. | last4 = Kwock | first4 = L. | title = Colloid cyst of the third ventricle: imaging-pathologic correlation. | journal = AJNR Am J Neuroradiol | volume = 21 | issue = 8 | pages = 1470-7 | month = Sep | year = 2000 | doi = | PMID = 11003281 }}</ref>
*Simple epithelium with ciliated cells and goblet cells.

====Images====
<gallery>
Image:Colloid_Cyst_HE_40x.jpg | Colloid cyst. (WC)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F4.expansion.html Colloid cyst (ajnr.org)].<ref name=pmid11003281/>

=Paediatric pathology=
==Kernicterus==
===General===
*Due to hyperbilirubinemia.<ref name=pmid7063283>{{Cite journal | last1 = Turkel | first1 = SB. | last2 = Miller | first2 = CA. | last3 = Guttenberg | first3 = ME. | last4 = Moynes | first4 = DR. | last5 = Godgman | first5 = JE. | title = A clinical pathologic reappraisal of kernicterus. | journal = Pediatrics | volume = 69 | issue = 3 | pages = 267-72 | month = Mar | year = 1982 | doi = | PMID = 7063283 }}</ref>

===Gross===
*Yellow staining:<ref name=npw>URL: [http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html]. Accessed on: 30 May 2012.</ref>
**Basal ganglia.<ref name=pmid10920171>{{Cite journal | last1 = Hansen | first1 = TW. | last2 = Hervieux | first2 = JF. | last3 = Orth | first3 = J. | last4 = Schmorl | first4 = CG. | last5 = Baumes | first5 = JB. | title = Pioneers in the scientific study of neonatal jaundice and kernicterus. | journal = Pediatrics | volume = 106 | issue = 2 | pages = E15 | month = Aug | year = 2000 | doi = | PMID = 10920171 }}</ref>
**Hippocampus.<ref name=pmid15091133>{{Cite journal | last1 = Paksoy | first1 = Y. | last2 = Koç | first2 = H. | last3 = Genç | first3 = BO. | title = Bilateral mesial temporal sclerosis and kernicterus. | journal = J Comput Assist Tomogr | volume = 28 | issue = 2 | pages = 269-72 | month = | year = | doi = | PMID = 15091133 }}</ref>
**Subthalamic nucleus.

Note:
*May not be specific.<ref name=pmid7063283/>

Image:
*[http://www.flickr.com/photos/neonatal-box/6275988844/ Kernicterus (flickr.com)].

===Microscopic===
Features - similar to [[HIE]]:<ref name=npw/>
*+/-Red neurons.
*+/-Gliosis.

==Joubert syndrome==
*Malformation of the cerebellar vermis.<ref name=ninds_joubert>[http://www.ninds.nih.gov/disorders/joubert/joubert.htm http://www.ninds.nih.gov/disorders/joubert/joubert.htm]</ref>

===Epidemiology===
*Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.<ref name=ninds_joubert/>

=Weird stuff=
==Acute disseminated encephalomyelitis==
*Abbreviated ''ADEM''.
{{Main|Acute disseminated encephalomyelitis}}

==Neuromyelitis optica==
*Abbreviated ''NMO''.
===General===
*Rare autoimmune disease - once considered a variant of [[multiple sclerosis]].
**Autoantibodies directed at aquaporin-4.<ref name=pmid22087205>{{Cite journal | last1 = Kim | first1 = W. | last2 = Kim | first2 = SH. | last3 = Kim | first3 = HJ. | title = New insights into neuromyelitis optica. | journal = J Clin Neurol | volume = 7 | issue = 3 | pages = 115-27 | month = Sep | year = 2011 | doi = 10.3988/jcn.2011.7.3.115 | PMID = 22087205 }}</ref>

Diagnosis:
*NMO-IgG.

Clinical - preferentially:
*Eye (optic neuritis).
*Spinal cord (myelitis).

===Microscopic===
Features:
*Inflammation - lymphocytes, macrophages.
*Reactive astrocytes.

Images:
*[http://path.upmc.edu/cases/case637.html Neuromyelitis optica - several images (upmc.edu)].

===IHC===
*Mixed lymphocyte population with CD3 > CD20.
*Aquaporin-4 loss.

==Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy==
*Commonly abbreviated ''CADASIL''.
{{Main|Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy}}

==Progressive multifocal leukoencephalopathy==
*Abbreviated ''PML''.
{{Main|Progressive multifocal leukoencephalopathy}}

=See also=
*[[Brain tumours]].
*[[Pituitary gland]].
*[[Histiocytoses]].
*[[Intracranial hematomas]].
*[[Spine]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
**[http://www.neuropathologyweb.org/test6/6test.html Quiz (neuropathologyweb.org)].
*[http://blog.lib.umn.edu/santa013/neuropathology/ Neuropathology cases (lib.umn.edu)].
*[http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 Neuropathology micrographs - identifying the site (stonybrookmedicalcenter.org)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/AAQuestion-41-60.htm Neurocytopathology quiz (ouhsc.edu)].
*[http://wiki.cns.org/wiki/index.php/Main_Page WikiCNS (wiki.cns.org)].

[[Category:Neuropathology]]

Neuropathology

2015-02-16T18:04:49Z

Ana: /* Brain tumours */

[[Image:MCA-Stroke-Brain-Human-2.JPG|thumb|right|Gross image showing changes of a [[stroke]]. (WC/Marvin 101)]]
This article is an introduction to '''neuropathology'''. There are separate articles for [[brain tumours]], the [[pituitary gland]], the [[spine]], the [[eye]], [[muscle pathologies]], [[neurohistology]] and [[neuroanatomy]].

Neuropathology is the bane of many anatomical pathologists in teaching hospitals... 'cause they have to fill in for the neuropathologist when he or she is on vacation.

==Neuroanatomy==
{{Main|Neuroanatomy}}
This is a large topic. It covered in a separate article, that also covers grossing.

==Neuroradiology==
Key factors to consider in evaluation:
*1) location
*2) number of lesions - single vs. multiple
*3) cystic vs. solid lesion
*4) enhancement

==Lesion location==
In neuroradiology and neuropathology, real estate is crucial. Lesion location can often narrow your differential.

Cortical lesions (gray matter):
* oligodendroglioma
* DNET
* ganglioglioma
* pleomorphic xanthoastrocytoma
* extraventricular ependymoma

Cortical-subcortical junction:
* metastases
* abscesses (hematogenous spread)

Subcortical lesions (white matter):
* glioblastoma
* diffuse gliomas
* demyelinating plaques

Deep gray matter lesions (e.g. basal ganglia);
* gliomas
* hypertensive hemorrhage

Cerebellar lesions:
* medulloblastoma
* pilocytic astrocytoma
* AT/RT

Intraventricular lesions:
* ependymoma
* subependymoma
* pilocytic astrocytoma
* central neurocytoma
* rosette forming glioneuronal tumour of the fourth ventricle

Suprasellar (above the pituitary):
* craniopharyngioma
* germinoma
* pilomyxoid astrocytoma

==Number of lesions==
If ''single'' lesion = think primary, neoplastic
If ''multiple'' lesions = think metastatic, neoplastic or infectious
'''NB: glioblastoma can be multifocal''' (and the foci can be quite far apart)

==Cystic vs. solid lesions==
Some tumours are classically cystic with a small solid component (so-called cyst with a mural nodule) -- e.g. pilocytic astrocytoma, ganglioglioma, hemangioblastoma

==Enhancing vs. non-enhancing:==
*In adults, enhancing generally = high grade.
*In pediatrics, it often depends on the pattern.
Two main patterns to be mindful of -- ring enhancing lesions, and cystic lesions with a mural nodule.

===Ring enhancing lesions===
In [[HIV]]/AIDS patients... mass on CT if infection:
*[[Toxoplasmosis]] - most common.<ref>MUN. Feb 3, 2009.</ref>

Ring enhancing lesion (DDx) - mnemonic ''MAGICAL DR'':<ref>{{Ref TN2005 |NS7}}</ref>
*Metstasis.
*Abscess.
*[[Glioblastoma]].
*[[Infarct]].
*Contusion.
*AIDS-related.
*[[Lymphoma]] + [[HIV]] assoc. disease (toxoplasma).
*Demyelination (e.g. [[multiple sclerosis]]).
*Resolving hematoma.

===Cyst with enhancing mural nodule===
*hemangioblastoma (#1 in adults)
*pilocytic astrocytoma (#1 in peds)
*pleomorphic xanthoastrocytoma
*ganglioglioma

==Grossing==
This is covered in the ''[[neuroanatomy]]'' article.

===Gross pathology===
The gross usually useless for arriving at a definitive diagnosis.

Exceptions:<ref>R. Kiehl. 8 November 2010.</ref>
*Sausage shape lesion of filum terminale = [[myxopapillary ependymoma]].
*Soft & tan colour = [[pituitary adenoma]].

==Normal histology==
{{main|Neurohistology}}
This is a big topic. It is covered in a separate article called ''[[neurohistology]]''.

==Histopathology==
===Neuronal changes===
====Anoxic neurons====
*[[AKA]] ''red neurons''.

Features:
*Intensely red cytoplasm.
*Pyknosis = nuclear shrinkage + darker staining.

=====Images=====
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons (WC)
Image:AcuteStroke_HE400x.jpg | Neurons in an acute stroke. (WC)
</gallery>
www:
*[http://neuropathology-web.org/chapter2/images2/2-anoxic.png Anoxic neurons (neuropathologyweb.org)].<ref>URL: [http://neuropathology-web.org/chapter2/chapter2aHIE.html http://neuropathology-web.org/chapter2/chapter2aHIE.html]. Accessed on: 10 December 2014.</ref>
*[http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-16.gif Anoxic neurons (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>

====Central chromatolysis====
Features:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html]. Accessed on: 22 December 2010.</ref>
*Central clearing.
**Nucleus and Nissl substance are pushed to cell periphery.

DDx:
*Axonal injury (traumatic).<ref name=pmid8909880>{{cite journal |author=Holland GR |title=Experimental trigeminal nerve injury |journal=Crit. Rev. Oral Biol. Med. |volume=7 |issue=3 |pages=237–58 |year=1996 |pmid=8909880 |doi= |url=}}</ref>
*Vitamin deficiency ([[pellagra]]).<ref name=pmid15577526>{{cite journal |author=Piercecchi-Marti MD, Pélissier-Alicot AL, Leonetti G, Tervé JP, Cianfarani F, Pellissier JF |title=Pellagra: a rare disease observed in a victim of mental and physical abuse |journal=Am J Forensic Med Pathol |volume=25 |issue=4 |pages=342–4 |year=2004 |month=December |pmid=15577526 |doi= |url=}}</ref>

=====Images=====
<gallery>
Image:Central_chromatolysis_-_intermed_mag_-_cropped.jpg | Central chromatolysis - intermed. mag. (WC)
Image:Central_chromatolysis_-_nf_-_very_high_mag.jpg | Central chromatolysis - NF stain - very high mag. (WC)
</gallery>
====Axonal swellings====
H&E:
*Eosinophilic (light pink) - ground glass-like appearance.
*Shape:
**Round if sectioned perpendicular to axis of axon.
***Bound by cell membrane.
***Large ~ typically 2-4x RBC diameter.
**Sausage-shaped if cut in along axis.

Images:
*[http://frontalcortex.com/gallery/pics/gliageek_VWMDx200.jpg Axonal swelling (frontalcortex.com)].<ref>URL: [http://frontalcortex.com/?page=oll&topic=24&qid=602 http://frontalcortex.com/?page=oll&topic=24&qid=602]. Accessed on: 3 November 2010.</ref>
*[http://www.neuropathologyweb.org/chapter3/images3/3-pvlaxonsweling.jpg Axonal swelling (neuropathologyweb.org)].

=====IHC=====
*APP.

Image:
*[http://vet.sagepub.com/content/37/6/677/F7.expansion.html Axonal swelling - APP (sagepub.com)].<ref>{{cite journal |author=Finnie JW, Manavis J, Blumbergs PC, Kuchel TR |title=Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin |journal=Vet. Pathol. |volume=37 |issue=6 |pages=677–80 |year=2000 |month=November |pmid=11105962 |doi= |url=http://vet.sagepub.com/content/37/6/677.full}}</ref>

===Glial changes===
====Astrocyte changes====
Reactive astrocytes:
*Approximately equally-spaced; distance between neighbouring astrocytes is ~2x (or more) the cell size.
*Well-defined cell border.
*Eosinophilic cytoplasm with many branching processes.
**Classically described as "funnel-shaped" in benign astrocytes.<ref>MUN. 15 November 2010.</ref>
*Peripheral nucleus.
<gallery>
Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg | Reactive astrocytes - high mag. (WC)
</gallery>

Alzheimer type II astrocyte:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 2 July 2010.</ref>
*Large cleared nucleus - '''key feature'''.
*Indistinct cytoplasm.
*Found in the context of ''hepatic encephalopathy'' in basal ganglia and lower layers of cortex.<ref name=Ref_Klatt202>{{Ref Klatt|202}}</ref>
*Images:
**[http://neuroquiz.com/?page=image&topic=1&qid=2714 Alzheimer type II astrocytes (neuroquiz.com)].
**[http://www.neuropathologyweb.org/chapter10/images10/10-AlzIIl.jpg Alzheimer type II astrocytes (neuropathologyweb.org)] .
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag.jpg| Alzheimer type II astrocytes. (WC)
</gallery>

Creutzfeldt cell:<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
*Finding associated with demyelinating disease.
*Image: [http://path.upmc.edu/cases/case336/images/fig03.jpg Crutzfeldt cell (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case336.html http://path.upmc.edu/cases/case336.html]. Accessed on: 15 January 2012.</ref>

Gemistocytic astrocytes:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 7 November 2010.</ref>
*Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:<ref name=Ref_MBNP173>{{Ref MBNP|173}}</ref>
*Cellular processes loaded with tau protein (as may be seen with tau [[IHC]] or Gallyas silver stain); Parisian-star-like appearance with special stain.
*+/-Multinucleated.
*A classic feature of ''[[progressive supranuclear palsy]]''.

====Other glial====
Bergmann gliosis (in the cerebellum):<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Thin layer of cells (2-3 cells) with open nuclei that are larger than granular cell layer nuclei; seen with Purkinje cell loss.

<gallery>
Image:Bergmann_gliosis_-_intermed_mag.jpg | Bergmann gliosis - intermed. mag. (WC)
Image:Bergmann_gliosis_-_high_mag.jpg | Bergmann gliosis - high mag. (WC)
Image:Metastatic_adenocarcinoma_-_cerebellum_-_intermed_mag.jpg | Bergmann gliosis due to compression by metastasis - intermed mag. (WC)
</gallery>
Image:
*[http://tpx.sagepub.com/content/35/5/676/F5.expansion.html Bergmann gliosis (sagepub.com)].

====Reactive change vs. malignancy====
Reactive changes vs. malignancy (mnemonic ''MIMICS''):<ref name=Ref_TPoSP254>{{Ref TPoSP|254}}</ref>
*'''MI'''crovesicular pattern.
*'''M'''itoses.
*'''I'''rregular spacing.
*'''C'''alcifications.
*'''S'''atellitosis, perineuronal.
**Large "crowds" of glial cells associated with nuclei.

===Inflammatory===
DDx:
*Autoimmune - [[Multiple sclerosis]].
*Neoplastic - [[Neuropathology tumours#CNS lymphoma|CNS lymphoma]].
*Infectious - [[HSV]].

====Encephalitis====
=====General=====
DDx:
*Viral encephalitis.
*Paraneoplastic syndromes.

=====Gross=====
*Frontal and temporal lobe - most common for HSV encephalitis.<ref>{{Ref APBR|416 Q47}}</ref>

=====Microscopic=====
Features:<ref name=pmid20051019>{{Cite journal | last1 = Takei | first1 = H. | last2 = Wilfong | first2 = A. | last3 = Malphrus | first3 = A. | last4 = Yoshor | first4 = D. | last5 = Hunter | first5 = JV. | last6 = Armstrong | first6 = DL. | last7 = Bhattacharjee | first7 = MB. | title = Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of the literature. | journal = Neuropathology | volume = 30 | issue = 4 | pages = 381-91 | month = Aug | year = 2010 | doi = 10.1111/j.1440-1789.2009.01079.x | PMID = 20051019 }}</ref>
*Perivascular inflammation.
*Microglia.
*+/-Neuronophagia.
**Phagocytosis of neurons.<ref>URL: [http://medical-dictionary.thefreedictionary.com/neuronophagia http://medical-dictionary.thefreedictionary.com/neuronophagia]. Accessed on: 11 April 2012.</ref>
*+/-Viral cytopathic changes.
*+/-Perineuronal inflammation.

Notes:
*Hemorrhage<ref name=pmid18246335>{{Cite journal | last1 = Vossough | first1 = A. | last2 = Zimmerman | first2 = RA. | last3 = Bilaniuk | first3 = LT. | last4 = Schwartz | first4 = EM. | title = Imaging findings of neonatal herpes simplex virus type 2 encephalitis. | journal = Neuroradiology | volume = 50 | issue = 4 | pages = 355-66 | month = Apr | year = 2008 | doi = 10.1007/s00234-007-0349-3 | PMID = 18246335 }}</ref> and necrosis - characteristic of HSV encephalitis.

Image:
*[http://neuropathology-web.org/chapter5/images5/5-21l.jpg HSV encephalitis (neuropathology-web.org)].<ref>URL: [http://neuropathology-web.org/chapter5/chapter5dViruses.html http://neuropathology-web.org/chapter5/chapter5dViruses.html]. Accessed on: 27 January 2012.</ref>

=====IHC=====
IHC stains for:
*Viral etiologies, e.g. [[HSV]], [[CMV]].
*Parasites, e.g. [[toxoplasma]].
*[[Fungi]], e.g. PASD.

===Architecture===
====Rosettes====
*Rosette = circular/flower-like arrangement of cells.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>

*Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**[[Ependymoma]].
**[[Medulloblastoma]], PNET.
**[[Central neurocytoma]].
**[[Glioblastoma]]s.

*Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**Medulloblastoma.
***Image: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Images/N1-TU-01-17.gif Medulloblastoma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17 http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17]. Accessed on: 3 December 2010.</ref>
**PNET (can be thought of as a supratentorial medulloblastoma) .

*Flexner-Wintersteiner rosette = rosette with empty centre (donut hole).<ref name=pmid16551982/>
**[[Retinoblastoma]]s.
**Pineoblastomas.
**Medulloepitheliomas.

*True ependymal rosette = surrounds a space.<ref name=pmid16551982/>
**[[Ependymoma]].

*Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**Similar to Homer-Wright rosette.
**[[Pineocytoma]].
**[[Neurocytoma]].

====Other====
*Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
**Key feature: variable thickness; helps separate from RBCs.
**Well-seen on trichrome stains.
<gallery>
Image:Rosenthal_HE_40x.jpg | Rosenthal fibres. (WP)
Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear (WC/AFIP)
</gallery>
*Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.<ref>{{Ref MBNP|11}}</ref>
**Image: [Image:Pilocytic_Micro.jpg EGBs (WC/AFIP)].
*Pseudopalisading - picket fence-like alignment of cells; long axis of cells perpendicular to interface with other structures/cells.
**Pseudopalisading of tumour cells (around necrotic regions) is seen in [[glioblastoma]].

Note:
*Good set of articles: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=Neuropathology%20for%20the%20neuroradiologist Neuropathology for radiologists (ncbi.nlm.nih.gov)].

===Inclusion bodies===
*Negri bodies.
**Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
**[[Rabies]].
<gallery>
Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg | Negri bodies. (WC/CDC)
</gallery>

*Lewy bodies.
**Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.<ref name=pmid15235805>{{cite journal |author=Marui W, Iseki E, Kato M, Akatsu H, Kosaka K |title=Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease |journal=Acta Neuropathol. |volume=108 |issue=2 |pages=121–8 |year=2004 |month=August |pmid=15235805 |doi=10.1007/s00401-004-0869-4 |url=}}</ref>
<gallery>
Image:Lewy_Koerperchen.JPG | Lewy body. (WC)
</gallery>
====Table of inclusions====
{| class="wikitable sortable"
! Feature
! Appearance
! Associated disease
! Comment
! Image
|-
| Grumous bodies [[AKA]] granular bodies
| granular and eosinophilic ~50 micrometers
| neurodegenerative disease, neuroaxonal dystrophies, aging
| ?Comment
| ?Image
|-
| Cowdry type 1 AKA Cowdry type A
| eosinophilic & round + halo
| [[herpes simplex virus]]
| can be confused with Lewy body, Marinesco body
| ?Image
|-
| Lewy body
| round cytoplasmic eosinophilic body +/- pale halo
| [[Parkinson disease]], dementia with Lewy bodies
| morphology dependent on location in brain; +ve for alpha-synuclein, alpha-B crystallin, ubiquitin
| [[Image:Lewy_Koerperchen.JPG |thumb|center|150px|]], [http://firstaidteam.com/usmlerximages/v/USMLERxLewy+bodies.gif.html]
|-
| Lafora body
| round
| myoclonic [[epilepsy]]
| look like corpora amylacea; location: dentate nucleus, liver, skeletal muscle, sweat glands
| ?Image
|-
| Lipofuscin
| yellow & granular
| aging
| olive, dendate
| ?Image
|-
| Negri body
| small eosinophic bodies
| rabies
| found in hippocampal neurons and Purkinje cells
| [[Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg|thumb|center|150px|]]
|-
| Hirano body
| concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron
| Alzheimer disease, Pick disease<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| actin crystals, may look like capillaries; location: CA1 of hippocampus
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adhirano.jpg]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>
|-
| Neurofibrillary tangles
| flame-shaped cytoplasmic thingy ~30 micrometers
| aging, Alzheimer's disease
| seen with silver stain
| [http://www.pakmed.net/academic/age/alz/plaques_tanglesBorder.jpg Schematic]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>, [http://faculty.washington.edu/alexbert/MEDEX/Fall/adtangle.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Granulovacuolar degeneration
| cytoplasmic vacuoles 4-5 micrometers
| ageing, [[Alzheimer's disease]], Pick's disease
| main found in Ammon horn<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adgvd.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Pick bodies
| round, homogenous, intracytoplasmic, ~10 micrometers
| [[Pick's disease]]
| pyramidal neurons, dentate granule cells (hippocampus); +ve for tau, tubulin, ubiquitin
| [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?action=view&current=Picks60x.jpg&mediafilter=images]
|-
| Bunina body
| size of Nissl granules, eosinophilic
| [[amyotrophic lateral sclerosis]] (ALS)
| EM: membrane-bound bodies; ubiquitin +ve
| [http://pathol.umin.ac.jp/gakubu/exam/2006jpg/19.jpg]
|-

|}

Image collection: [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?mediafilter=images Inclusion bodies (photobucket.com)].

==Immunohistochemistry==
{{Main|Immunohistochemistry}}
===General===
*S-100.
**Sensitive... but non-specific, e.g. also stains [[melanoma]].

===Glial===
*GFAP (glial fibrillary acidic protein) - should stain perikaryon.

====Glial tumours====
Standard work-up:
*GFAP.
*p53.
*Ki-67.

===Neuronal===
*Synaptophysin.
*Chromogranin.

===Carcinoma vs. glial tumours===
*AE1/AE3 often +ve in glial tumours (e.g. astrocytomas, oligodendrogliomas); CAM5.2 is usu. -ve in glial tumours.<ref name=Ref_PSNP_12>{{Ref PSNP|12}}</ref>

===Others===
*APP (amyloid precursor protein) - detects axonal swellings.
*NF (neurofilament) - detects axonal swellings.

=Brain tumours=
{{main|Neuropathology tumours}}
Tumours are a big part of neuropathology. The most common brain tumour (in adults) is a metastasis. The most common primary tumour (in adults) is glioblastoma which has a horrible prognosis.

=Non-tumour=
==Cerebral hemorrhage==
:See: ''[[Intracranial hematoma]]'' for intracranial bleeds

Includes discussion of:
*[[Epidural hematoma]].
*[[Subdural hematoma]].
*[[Subarachnoid hematoma]].
*[[Intracerebral hematoma]]s.

==Duret hematoma==
*[[AKA]] Duret hemorrhage.
===General===
*Bleed in the upper brainstem (midbrain and pons).
**Thought to be due to transtentorial herniation secondary to supratentorial mass effect (e.g. supratentorial tumour, [[intracranial hemorrhage]]).<ref name=pmid11819006>{{Cite journal | last1 = Parizel | first1 = PM. | last2 = Makkat | first2 = S. | last3 = Jorens | first3 = PG. | last4 = Ozsarlak | first4 = O. | last5 = Cras | first5 = P. | last6 = Van Goethem | first6 = JW. | last7 = van den Hauwe | first7 = L. | last8 = Verlooy | first8 = J. | last9 = De Schepper | first9 = AM. | title = Brainstem hemorrhage in descending transtentorial herniation (Duret hemorrhage). | journal = Intensive Care Med | volume = 28 | issue = 1 | pages = 85-8 | month = Jan | year = 2002 | doi = 10.1007/s00134-001-1160-y | PMID = 11819006 }}</ref>
*Often fatal.<ref name=pmid11098635>{{Cite journal | last1 = Fujimoto | first1 = Y. | last2 = Aguiar | first2 = PH. | last3 = Freitas | first3 = AB. | last4 = de Andrade | first4 = AF. | last5 = Marino Júnior | first5 = R. | title = Recovery from Duret hemorrhage: a rare complication after craniotomy--case report. | journal = Neurol Med Chir (Tokyo) | volume = 40 | issue = 10 | pages = 508-10 | month = Oct | year = 2000 | doi = | PMID = 11098635 }}</ref>
===Gross===
*Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).<ref name=pmid11819006/>

Image:
*[http://library.med.utah.edu/WebPath/jpeg5/CNS037.jpg Duret hemorrhage (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html]. Accessed on: 4 December 2011.</ref>

===Microscopic===
Features:
*RBC extravasation.
*+/-Hemosiderin-laden macrophages.
*+/-Ischemic neurons.

==Alcohol & CNS==
===Clinical===
*Wernicke's encephalopathy
**Mnemonic ''WACO'':
***Wernicke's.
***Ataxia.
***Confusion, confabulation -- Korsakoff.
***Ocular Sx (CN IV palsy).
**Cause: thiamine deficiency.

===Pathology===
Features:<ref>http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract</ref>
*Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex<ref>URL: [http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939 http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939]. Accessed on: 22 September 2010.</ref> usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>
*Central pontine myelinolysis (CPM).<ref name=pmid21085565>{{cite journal |author=Campbell MC |title=Hyponatremia and central pontine myelinolysis as a result of beer potomania: a case report |journal=Prim Care Companion J Clin Psychiatry |volume=12 |issue=4 |pages= |year=2010 |pmid=21085565 |pmc=2983455 |doi=10.4088/PCC.09l00936ecr |url=}}</ref>
**Just what it sound like - myelin loss in the central pons.
**Classically associated with rapid correction of hyponatremia.<ref>{{cite journal |author=Bernsen HJ, Prick MJ |title=Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia |journal=Acta Neurol Belg |volume=99 |issue=3 |pages=189–93 |year=1999 |month=September |pmid=10544728 |doi= |url=}}</ref>
*Mammillary body shrinkage.<ref name=pmid8947329>{{cite journal |author=Shear PK, Sullivan EV, Lane B, Pfefferbaum A |title=Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia |journal=Alcohol. Clin. Exp. Res. |volume=20 |issue=8 |pages=1489-95 |year=1996 |month=November |pmid=8947329 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=1996&volume=20&issue=8&spage=1489}}</ref>
*Anterior cerebellar vermis atrophy; weak finding - as also age-related.<ref name=pmid3478969>{{cite journal |author=Torvik A |title=Brain lesions in alcoholics: neuropathological observations |journal=Acta Med. Scand. Suppl. |volume=717 |issue= |pages=47–54 |year=1987 |pmid=3478969 |doi= |url=}}</ref>
**Vermis atrophy is also seen in schizophrenia.<ref name=pmid1938163>{{cite journal |author=Sandyk R, Kay SR, Merriam AE |title=Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia |journal=Int. J. Neurosci. |volume=57 |issue=3-4 |pages=205–12 |year=1991 |month=April |pmid=1938163 |doi= |url=}}</ref>

====Marchiafava-Bignami Disease====
*Rare.
*Demyelination of the corpus callosum.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>

====Wernicke's encephalopathy====
General:
*Due to thiamine deficiency.
**Malnourishment often accompanies [[alcoholism]].

Features:<ref name=pmid3929155>{{Cite journal | last1 = Torvik | first1 = A. | title = Two types of brain lesions in Wernicke's encephalopathy. | journal = Neuropathol Appl Neurobiol | volume = 11 | issue = 3 | pages = 179-90 | month = | year = | doi = | PMID = 3929155 }}</ref>
*Neurons of mammillary bodies preserved - '''key'''.
*Loss of myelin.
*Hemorrhage.
*Edema.
*Reactive blood vessels.

Note:
*The thalamus and inferior olives show neuronal loss.<ref name=pmid3929155/>

====Common non-specific findings====
*[[Intracranial haemorrhage]] - due to trauma.

==Meningitis==
===General===
*Definition: inflammation of the meninges (pia mater, arachnoid membranes, dura mater).

Classic clinical presentation:
*Neck stiffness.
*Fever.
*+/-Headache.
*+/-Decreased level of consciousness.

CSF findings:
{| class="wikitable sortable"
! Type
! Glucose
! Protein
! Cells
|-
| Bacterial, acute
| low
| high
| neutrophils
|-
| Viral
| normal
| slight elevation
| lymphocytes
|}

====Etiology====
*Infectious.
**Bacterial.
**Viral.
**Parasitic
*Autoimmune.
*Toxic.
*Aseptic - see ''[[Mollaret's meningitis]]''.

Bacterial meningitis - most probably cause by age:<ref>{{Ref PCPBoD8|666-7}}</ref>
{| class="wikitable sortable"
! Age
! Organism
|-
| Neonate
| ''Escherichia coli'', Group B Streptococcus
|-
| Infants, children
| ''Streptococcus pneumoniae''
|-
| Adolescents, young adults
| ''Neisseria meningitidis''
|-
| Elderly
| ''Streptococcus pneumoniae'', ''Listeria monocytogenes''
|}

===Gross===
Features:
*+/-Clouded appearance of the meninges.
*+/-Pus.
*+/-Petechiae.
*+/-Cerebral edema.

====Image====
<gallery>
Image:Streptococcus_pneumoniae_meningitis,_gross_pathology_33_lores.jpg | Meningitis. (WC)
</gallery>

===Microscopic===
Features:
*Inflammation of the meninges:
**+/-[[Neutrophil]]s.
**+/-Lymphocytes.
**+/-[[Plasma cell]]s.
*+/-Microorganisms (infectious meningitis):
**Bacteria.
**[[Fungi]], e.g. [[aspergillosis]] (may be intravascular).

Main DDx:
*[[Lymphoma]].

====Image====
<gallery>
Image:Meningitis_Histopathology.jpg | Bacterial meningitis. (WC)
</gallery>

==Cerebral abscess==
===General===
*May mimic malignancy clinically.

===Microscopic===
Features:
*Sheets of neutrophils surrounded by fibrosing brain.
**Fibrosing brain: pale (lighter pink than normal brain tissue), dense.

Images:
*[http://pathology.class.kmu.edu.tw/ch01/4-1.jpg Cerebral abscess - very low mag. (kmu.edu.tw)].<ref>URL: [http://pathology.class.kmu.edu.tw/ch01/Slide4.htm http://pathology.class.kmu.edu.tw/ch01/Slide4.htm]. Accessed on: 1 January 2012.</ref>
*[http://pathology.class.kmu.edu.tw/ch01/4-5.jpg Cerebral abscess - low mag. (kmu.edu.tw)].

==Neurodegenerative diseases==
{{Main|Neurodegenerative diseases}}
This is a hueueuge topic. It is covered in its own article and includes a general discussion of dementia.

==Epilepsy==
{{Main|Epilepsy}}

==Cerebrovascular accident==
*Abbreviated ''CVA''.
*[[AKA]] ''stroke''.
{{Main|Cerebrovascular accident}}

==Hypoxic-ischemic encephalopathy==
*Abbreviated ''HIE''.
{{Main|Hypoxic-ischemic encephalopathy}}

==Multiple sclerosis==
*Abbreviated ''MS''.
{{Main|Multiple sclerosis}}

==Cerebral amyloid angiopathy==
===General===
*Abbreviated ''CAA''.
*Disease of the old.
*Strong association with ''[[lobar haemorrhage]]'' (bleeds of the cerebellar cortex and cerebral cortex).<ref name=pmid16982664>{{cite journal |author=Thanvi B, Robinson T |title=Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage in older people |journal=Age Ageing |volume=35 |issue=6 |pages=565–71 |year=2006 |month=November |pmid=16982664 |doi=10.1093/ageing/afl108 |url=}}</ref>

Etiology:
*[[Amyloid]] deposition in the basal lamina of smooth muscle (in the cerebellar cortex and cerebral cortex).

===Gross===
*Bleeds typically superficial (cortex and subcortical white matter) and in the frontal lobe or parietal lobe.<ref name=pmid17297004>{{Cite journal | last1 = Haacke | first1 = EM. | last2 = DelProposto | first2 = ZS. | last3 = Chaturvedi | first3 = S. | last4 = Sehgal | first4 = V. | last5 = Tenzer | first5 = M. | last6 = Neelavalli | first6 = J. | last7 = Kido | first7 = D. | title = Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging. | journal = AJNR Am J Neuroradiol | volume = 28 | issue = 2 | pages = 316-7 | month = Feb | year = 2007 | doi = | PMID = 17297004 | URL = http://www.ajnr.org/content/28/2/316.long }}</ref>

===Microscopic===
Features:
*Amorphous, acellular eosinophilic material within walls of small arteries.
**This is a high power diagnosis with congo red staining.

Notes:
*Amyloidosis is seen in all individuals with [[Alzheimer's disease]]; the amount of amyloid is what differs -- in CAA it is lots and lots.
*The white matter is typically spared by CAA.<ref name=pmid19225408>{{Cite journal | last1 = Schröder | first1 = R. | last2 = Deckert | first2 = M. | last3 = Linke | first3 = RP. | title = Novel isolated cerebral ALlambda amyloid angiopathy with widespread subcortical distribution and leukoencephalopathy due to atypical monoclonal plasma cell proliferation, and terminal systemic gammopathy. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 3 | pages = 286-99 | month = Mar | year = 2009 | doi = 10.1097/NEN.0b013e31819a87f9 | PMID = 19225408 }}
</ref>

====Images====
<gallery>
Image:Cerebral_amyloid_angiopathy_-_very_high_mag.jpg |CAA - congo red - very high mag. (WC)
Image:Cerebral_amyloid_angiopathy_-_low_mag.jpg |CAA - congo red - low mag. (WC)
Image:Cerebral_amyloid_angiopathy_-2b-_amyloid_beta_-_high_mag.jpg |CAA - beta-amyloid - high mag. (WC)
</gallery>
===Stains===
*[[Congo red]].

===IHC===
*Abeta-amyloid (AKA beta-amyloid).

==Central pontine myelinolysis==
*Abbreviated ''CPM''.
*[[AKA]] ''pontine myelinolysis''.
===General===
*Classically in the pons, ergo "pontine" is in the name.
*Classically midline, ergo "central" is in the name.
**May occur elsewhere -- known as ''extrapontine myelinolysis''.

Etiology:
*Rapid correction of hyponatremia.<ref name=pmid22080394>{{Cite journal | last1 = Chang | first1 = Y. | last2 = An | first2 = DH. | last3 = Xing | first3 = Y. | last4 = Qi | first4 = X. | title = Central pontine and extrapontine myelinolysis associated with acute hepatic dysfunction. | journal = Neurol Sci | volume = | issue = | pages = | month = Nov | year = 2011 | doi = 10.1007/s10072-011-0838-3 | PMID = 22080394 }}</ref>
*Tacrolimus post-liver transplant.<ref name=pmid21959523>{{Cite journal | last1 = Fukazawa | first1 = K. | last2 = Nishida | first2 = S. | last3 = Aguina | first3 = L. | last4 = Pretto | first4 = E. | title = Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation. | journal = Ann Transplant | volume = 16 | issue = 3 | pages = 139-42 | month = Sep | year = 2011 | doi = | PMID = 21959523 }}</ref>
*Associated with [[alcoholism]] and malnourishment.

Clinical:<ref>{{Cite journal | last1 = Lai | first1 = CC. | last2 = Tan | first2 = CK. | last3 = Lin | first3 = SH. | last4 = Chen | first4 = HW. | title = Central pontine myelinolysis. | journal = CMAJ | volume = 183 | issue = 9 | pages = E605 | month = Jun | year = 2011 | doi = 10.1503/cmaj.090186 | PMID = 21543311 | PMC = 3114939 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114939/?tool=pubmed }}</ref>
*Decreased level of consciousness - most common.
*Quadriplegia.
*Poor prognosis.

===Microscopic===
Features:<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*Myelin loss.
*No inflammation.
*Relative preservation of neurons.

Images:
*[http://neuropathology-web.org/chapter6/images6/6-9l.jpg CPM (neuropathology-web.org)].<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*[http://dartmed.dartmouth.edu/spring09/html/virtual_microscopy_we/ CPM (dartmouth.edu)].

==Vascular malformations==
{{Main|Vascular malformations}}
Types:<ref name=pmid17076525>{{cite journal |author=Prayson RA, Kleinschmidt-DeMasters BK |title=An algorithmic approach to the brain biopsy--part II |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1639–48 |year=2006 |month=November |pmid=17076525 |doi= |url=}}</ref>
#Arteriovenous malformation.
#*Most important clinically - highest risk of bleeding.
#Varix.
#*One large (dilated) vein.
#Venous angioma.
#*Many small veins.
#Cavernous malformation.
#*Vessels are back-to-back (no intervening parenchyma).

Also see: ''[[Sturge-Weber syndrome]]''.

=Cysts=
===General===
*All are "benign", but some may be fatal due to spatial constraints.

===List of cysts===
*[[Colloid cyst]].
**Columnar epithelium.
*Arachnoid cyst - considered precursor of [[meningioma]].
**[[Psammoma bodies]].
**Clumps of cells.
**Whorled pattern.
*[[Dermoid cyst]].
**Skin + adnexal structures.
**... think of ovarian dermoid.
*Epidermoid cyst.
*Choroid plexus cyst.
*Neuroenteric cyst.
**Foregut cyst with connection to dura.<ref>URL: [http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm]. Accessed on: 19 December 2011.</ref>
***Gastrointestinal tract epithelium.
***Usually seen with vertebral anomalies.
*Epithelial cyst.
*Others.

==Colloid cyst==
===General===
Classic presentation:<ref name=pmid15228889>{{Cite journal | last1 = Spears | first1 = RC. | title = Colloid cyst headache. | journal = Curr Pain Headache Rep | volume = 8 | issue = 4 | pages = 297-300 | month = Aug | year = 2004 | doi = | PMID = 15228889 }}</ref>
*Headache - may be relieved by lying down.
*Can cause [[sudden natural death]].<ref name=pmid14716130>{{Cite journal | last1 = Kava | first1 = MP. | last2 = Tullu | first2 = MS. | last3 = Deshmukh | first3 = CT. | last4 = Shenoy | first4 = A. | title = Colloid cyst of the third ventricle: a cause of sudden death in a child. | journal = Indian J Cancer | volume = 40 | issue = 1 | pages = 31-3 | month = | year = | doi = | PMID = 14716130 }}</ref>

===Gross===
*Fluid filled cyst - classically in the third ventricle.

====Images====
<gallery>
Image:Human brain showning a colloid cyst in the third ventricle.jpg| Colloid cyst at autopsy. (Shaktawat ''et al.''<ref name=pmid16867192>{{Cite journal | last1 = Shaktawat | first1 = SS. | last2 = Salman | first2 = WD. | last3 = Twaij | first3 = Z. | last4 = Al-Dawoud | first4 = A. | title = Unexpected death after headache due to a colloid cyst of the third ventricle. | journal = World J Surg Oncol | volume = 4 | issue = | pages = 47 | month = | year = 2006 | doi = 10.1186/1477-7819-4-47 | PMID = 16867192 }}</ref>)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F3.expansion.html Colloid cyst of third ventricle (ajnr.org)].<ref name=pmid11003281/>

===Microscopic===
Features:<ref name=pmid11003281>{{Cite journal | last1 = Armao | first1 = D. | last2 = Castillo | first2 = M. | last3 = Chen | first3 = H. | last4 = Kwock | first4 = L. | title = Colloid cyst of the third ventricle: imaging-pathologic correlation. | journal = AJNR Am J Neuroradiol | volume = 21 | issue = 8 | pages = 1470-7 | month = Sep | year = 2000 | doi = | PMID = 11003281 }}</ref>
*Simple epithelium with ciliated cells and goblet cells.

====Images====
<gallery>
Image:Colloid_Cyst_HE_40x.jpg | Colloid cyst. (WC)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F4.expansion.html Colloid cyst (ajnr.org)].<ref name=pmid11003281/>

=Paediatric pathology=
==Kernicterus==
===General===
*Due to hyperbilirubinemia.<ref name=pmid7063283>{{Cite journal | last1 = Turkel | first1 = SB. | last2 = Miller | first2 = CA. | last3 = Guttenberg | first3 = ME. | last4 = Moynes | first4 = DR. | last5 = Godgman | first5 = JE. | title = A clinical pathologic reappraisal of kernicterus. | journal = Pediatrics | volume = 69 | issue = 3 | pages = 267-72 | month = Mar | year = 1982 | doi = | PMID = 7063283 }}</ref>

===Gross===
*Yellow staining:<ref name=npw>URL: [http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html]. Accessed on: 30 May 2012.</ref>
**Basal ganglia.<ref name=pmid10920171>{{Cite journal | last1 = Hansen | first1 = TW. | last2 = Hervieux | first2 = JF. | last3 = Orth | first3 = J. | last4 = Schmorl | first4 = CG. | last5 = Baumes | first5 = JB. | title = Pioneers in the scientific study of neonatal jaundice and kernicterus. | journal = Pediatrics | volume = 106 | issue = 2 | pages = E15 | month = Aug | year = 2000 | doi = | PMID = 10920171 }}</ref>
**Hippocampus.<ref name=pmid15091133>{{Cite journal | last1 = Paksoy | first1 = Y. | last2 = Koç | first2 = H. | last3 = Genç | first3 = BO. | title = Bilateral mesial temporal sclerosis and kernicterus. | journal = J Comput Assist Tomogr | volume = 28 | issue = 2 | pages = 269-72 | month = | year = | doi = | PMID = 15091133 }}</ref>
**Subthalamic nucleus.

Note:
*May not be specific.<ref name=pmid7063283/>

Image:
*[http://www.flickr.com/photos/neonatal-box/6275988844/ Kernicterus (flickr.com)].

===Microscopic===
Features - similar to [[HIE]]:<ref name=npw/>
*+/-Red neurons.
*+/-Gliosis.

==Joubert syndrome==
*Malformation of the cerebellar vermis.<ref name=ninds_joubert>[http://www.ninds.nih.gov/disorders/joubert/joubert.htm http://www.ninds.nih.gov/disorders/joubert/joubert.htm]</ref>

===Epidemiology===
*Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.<ref name=ninds_joubert/>

=Weird stuff=
==Acute disseminated encephalomyelitis==
*Abbreviated ''ADEM''.
{{Main|Acute disseminated encephalomyelitis}}

==Neuromyelitis optica==
*Abbreviated ''NMO''.
===General===
*Rare autoimmune disease - once considered a variant of [[multiple sclerosis]].
**Autoantibodies directed at aquaporin-4.<ref name=pmid22087205>{{Cite journal | last1 = Kim | first1 = W. | last2 = Kim | first2 = SH. | last3 = Kim | first3 = HJ. | title = New insights into neuromyelitis optica. | journal = J Clin Neurol | volume = 7 | issue = 3 | pages = 115-27 | month = Sep | year = 2011 | doi = 10.3988/jcn.2011.7.3.115 | PMID = 22087205 }}</ref>

Diagnosis:
*NMO-IgG.

Clinical - preferentially:
*Eye (optic neuritis).
*Spinal cord (myelitis).

===Microscopic===
Features:
*Inflammation - lymphocytes, macrophages.
*Reactive astrocytes.

Images:
*[http://path.upmc.edu/cases/case637.html Neuromyelitis optica - several images (upmc.edu)].

===IHC===
*Mixed lymphocyte population with CD3 > CD20.
*Aquaporin-4 loss.

==Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy==
*Commonly abbreviated ''CADASIL''.
{{Main|Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy}}

==Progressive multifocal leukoencephalopathy==
*Abbreviated ''PML''.
{{Main|Progressive multifocal leukoencephalopathy}}

=See also=
*[[Brain tumours]].
*[[Pituitary gland]].
*[[Histiocytoses]].
*[[Intracranial hematomas]].
*[[Spine]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
**[http://www.neuropathologyweb.org/test6/6test.html Quiz (neuropathologyweb.org)].
*[http://blog.lib.umn.edu/santa013/neuropathology/ Neuropathology cases (lib.umn.edu)].
*[http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 Neuropathology micrographs - identifying the site (stonybrookmedicalcenter.org)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/AAQuestion-41-60.htm Neurocytopathology quiz (ouhsc.edu)].
*[http://wiki.cns.org/wiki/index.php/Main_Page WikiCNS (wiki.cns.org)].

[[Category:Neuropathology]]

Neuropathology tumours

2015-02-16T18:03:02Z

Ana: /* Children */

[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''. Tumours are a large part of [[neuropathology]]. [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.

There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===Adult===
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]] (previously known as ''glioblastoma multiforme'').
# [[Anaplastic astrocytoma]].
# [[Meningioma]].

===Children===
# Pilocytic astrocytoma.
# [[Medulloblastoma]].
# [[Ependymoma]].

===Location (most common)===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
*Cerebrum:
**Cortical based - [[oligodendroglioma]].
**Grey-white junction - metastases.
**White matter - astrocytoma, [[glioblastoma]].
**Periventricular - CNS lymphoma.
**Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
*Cerebellum:
**Midline/central - [[medulloblastoma]].
**Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
**Solid lesion (older individual) - [[metastasis]].
*Spinal cord:
**[[Ependymoma]], glioblastoma.
**Filum terminale - [[myxopapillary ependymoma]], [[paraganglioma]].

====Filum terminale====
*Filum terminale = bottom end of the spinal cord - has a limited differential.

DDx:<ref>JLK. 31 May 2010.</ref>
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].

====Cerebellopontine angle====
*Abbreviated ''CP angle''.

DDx:<ref>R. Kiehl. 8 November 2010.</ref>
*[[Schwannoma]].
*[[Meningioma]].
*[[Dermoid cyst]]/epidermoid cyst.
*[[Ependymoma]].
*[[Choroid plexus papilloma]].

===Cystic tumours===
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>

===Primary versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
Glial tumours:
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain.

[[Lymphoma]]:
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.

====Secondary====
Carcinomas:
*Well-demarcated border between brain and lesion - '''key feature'''.
*No cytoplasmic processes.
*Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
*+/-Glandular arrangement.
*+/-Nucleoli.

===Common neuropathology tumours in a table===
{| class="wikitable"
|'''Type'''
|'''Key feature(s)'''
|'''Imaging'''
|'''History'''
|'''Notes'''
|'''IHC'''
|'''Images'''
|-
|Normal tissue
|cells regularly spaced, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion?
|nil
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|nil
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|Infiltrative [[astrocytoma]] ([[WHO]] grade II or grade III)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|[[Glioblastoma]] (WHO grade IV)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|usu. old
|often suspected to have metastatic disease
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

==Infiltrative astrocytomas==
{{Main|Astrocytoma}}

===Overview===
*Low-grade (diffuse) astrocytomas (Grade II).
*Anaplastic astrocytomas (Grade III).
*[[Glioblastoma]] (Grade IV).

Notes:
*Non-infiltrative gliomas:
**[[Pilocytic astrocytoma]] (WHO Grade I).
**[[Dysembryoplastic neuroepithelial tumour]] (DNT), (WHO Grade I).

===Microscopic===
Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no glial processes.
*Rosenthal fibres within the tumour... make it into a [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>

====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).

Mitotic figures present:
*At least grade III (anaplastic astrocytoma).

Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).

Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.

====Images====
Glioblastoma:
<gallery>
Image:Glioblastoma_%281%29.jpg | Glioblastoma - pseudopalisading of tumour cells (WC)
Image:Glioblastoma_-_high_mag.jpg | Glioblastoma with fragment of near-normal white matter - high mag. (WC)
</gallery>
Anaplastic astrocytoma:
<gallery>
Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | Anaplastic astrocytoma - very high mag. (WC)
Image:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg | Anaplastic astrocytoma - GFAP - very high mag. (WC)
</gallery>

=====Table of common gliomas - grading=====
Histomorphologic comparison of common gliomas:
{| class="wikitable"
|'''Entity''' || '''Rosenthal fibres / EGBs''' ||'''Nuclear atypia''' ||'''Mitoses''' || '''Necrosis or MVP''' || '''Infiltrative''' || '''Image'''
|-
|Pilocytic astrocytoma || yes || usu. no || usu. no || usu. no || no || [[Image:Rosenthal_HE_40x.jpg|thumb|150px]]
|-
|Low-grade astrocytoma || no || yes || no || no || yes || image?
|-
|Anaplastic astrocytoma || no || yes || yes || no || yes || [[Image:Anaplastic_astrocytoma_-_high_mag.jpg|thumb|150px]]
|-
|Glioblastoma || no || yes || yes || yes || yes || [[Image:Glioblastoma_-_high_mag.jpg|thumb|150px]]
|}
Notes:
*''MVP'' = microvascular proliferation.
*''EGBs'' = eosinophilic granular bodies.

===IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane).
*Ki-67 - usu. high >20% of cells.
*p53 - often +ve.
*IDH1 (isocitrate dehydrogenase 1).
**+ve in tumours that arose from low-grade gliomas.<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref>
***Image: [http://en.wikipedia.org/wiki/File:IDH1_GBM_20x.jpg IDH1 +ve in glioblastoma (WP)].

Notes:
*IDH1 and IDH2 mutations - better survival.<ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>

==Pilocytic astrocytoma==
{{Main|Pilocytic astrocytoma}}

==Pleomorphic xanthoastrocytoma==
*Abbreviated ''PXA''.
{{Main|Pleomorphic xanthoastrocytoma}}

==Dysembryoplastic neuroepithelial tumour==
*Abbreviated ''DNT''.
{{Main|Dysembryoplastic neuroepithelial tumour}}

==Subependymal giant cell astrocytoma==
*Abbreviated ''SEGA''.
{{Main|Subependymal giant cell astrocytoma}}

==Pilomyxoid astrocytoma==
{{Main|Pilomyxoid astrocytoma}}

==Atypical teratoid/rhabdoid tumour==
:See also: ''[[Extrarenal malignant rhabdoid tumour]]''.
*Commonly abbreviated ''AT/RT''.
*May be written ''atypical teratoid rhabdoid tumour'', i.e. without the forward slash, or ''atypical teratoid-rhabdoid tumour'' (AT-RT).
{{Main|Atypical teratoid/rhabdoid tumour}}

==Oligodendroglioma==
{{Main|Oligodendroglioma}}

==Oligoastrocytoma==
{{Main|Oligoastrocytoma}}

==Meningioma==
{{Main|Meningioma}}

==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
*Benign:
**[[Schwannoma]].
**[[Neurofibroma]].
**[[Perineurioma]].
**[[Traumatic neuroma]].
*Malignant:
**[[Malignant peripheral nerve sheath tumour]] (MPNST).

==Schwannoma==
{{Main|Schwannoma}}

==Neurofibroma==
{{Main|Neurofibroma}}

==Ganglioneuroma==
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}

==Ependymoma==
{{Main|Ependymoma}}

==Subependymoma==
{{Main|Subependymoma}}

==Choroid plexus papilloma==
{{Main|Choroid plexus papilloma}}

==Choroid plexus carcinoma==
{{Main|Choroid plexus carcinoma}}

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==Medulloblastoma==
{{Main|Medulloblastoma}}
*Tumour of cerebellum - key feature.
*Morphologically identical supratentorial tumours are called [[primitive neuroectodermal tumour]] (PNET).

==Primitive neuroectodermal tumour==
{{Main|Primitive neuroectodermal tumour}}

==Embryonal tumour with abundant neuropil and true rosettes==
*Abbreviated ''ETANTR''.
{{Main|Embryonal tumour with abundant neuropil and true rosettes}}

==CNS lymphoma==
Classification:
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.

===General - primary CNS===
*Classically periventicular distribution.
*Usually large B cell; can be considered a type of [[diffuse large B cell lymphoma]] (DLBCL).
**Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>

===Microscopic===
Features:
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*Perivascular clustering.

====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>

===IHC===
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>

Common pattern:
*CD20 +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-1 -ve.

==Neurocytoma==
{{Main|Neurocytoma}}

==Central neurocytoma==
*Abbreviated ''CNC''.
{{Main|Central neurocytoma}}

==Ganglioglioma==
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
===General===
*Rare.
*Usu. temporal lobe.
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi = | PMID = 12125968 }}</ref>

===Microscopic===
Features:
*Atypical neurons.
*Atypical glia.

Images:
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].

==Lhermitte-Duclos disease==
*Abbreviated ''LDD''.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.

Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].

===IHC===
*NSE +ve -- small cells.

==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.

==See also==
*[[Neuropathology]].
*[[Muscle biopsy]].

==References==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].

[[Category:Neuropathology]]

Neuropathology

2015-02-16T17:54:50Z

Ana: /* Neuroradiology */

[[Image:MCA-Stroke-Brain-Human-2.JPG|thumb|right|Gross image showing changes of a [[stroke]]. (WC/Marvin 101)]]
This article is an introduction to '''neuropathology'''. There are separate articles for [[brain tumours]], the [[pituitary gland]], the [[spine]], the [[eye]], [[muscle pathologies]], [[neurohistology]] and [[neuroanatomy]].

Neuropathology is the bane of many anatomical pathologists in teaching hospitals... 'cause they have to fill in for the neuropathologist when he or she is on vacation.

==Neuroanatomy==
{{Main|Neuroanatomy}}
This is a large topic. It covered in a separate article, that also covers grossing.

==Neuroradiology==
Key factors to consider in evaluation:
*1) location
*2) number of lesions - single vs. multiple
*3) cystic vs. solid lesion
*4) enhancement

==Lesion location==
In neuroradiology and neuropathology, real estate is crucial. Lesion location can often narrow your differential.

Cortical lesions (gray matter):
* oligodendroglioma
* DNET
* ganglioglioma
* pleomorphic xanthoastrocytoma
* extraventricular ependymoma

Cortical-subcortical junction:
* metastases
* abscesses (hematogenous spread)

Subcortical lesions (white matter):
* glioblastoma
* diffuse gliomas
* demyelinating plaques

Deep gray matter lesions (e.g. basal ganglia);
* gliomas
* hypertensive hemorrhage

Cerebellar lesions:
* medulloblastoma
* pilocytic astrocytoma
* AT/RT

Intraventricular lesions:
* ependymoma
* subependymoma
* pilocytic astrocytoma
* central neurocytoma
* rosette forming glioneuronal tumour of the fourth ventricle

Suprasellar (above the pituitary):
* craniopharyngioma
* germinoma
* pilomyxoid astrocytoma

==Number of lesions==
If ''single'' lesion = think primary, neoplastic
If ''multiple'' lesions = think metastatic, neoplastic or infectious
'''NB: glioblastoma can be multifocal''' (and the foci can be quite far apart)

==Cystic vs. solid lesions==
Some tumours are classically cystic with a small solid component (so-called cyst with a mural nodule) -- e.g. pilocytic astrocytoma, ganglioglioma, hemangioblastoma

==Enhancing vs. non-enhancing:==
*In adults, enhancing generally = high grade.
*In pediatrics, it often depends on the pattern.
Two main patterns to be mindful of -- ring enhancing lesions, and cystic lesions with a mural nodule.

===Ring enhancing lesions===
In [[HIV]]/AIDS patients... mass on CT if infection:
*[[Toxoplasmosis]] - most common.<ref>MUN. Feb 3, 2009.</ref>

Ring enhancing lesion (DDx) - mnemonic ''MAGICAL DR'':<ref>{{Ref TN2005 |NS7}}</ref>
*Metstasis.
*Abscess.
*[[Glioblastoma]].
*[[Infarct]].
*Contusion.
*AIDS-related.
*[[Lymphoma]] + [[HIV]] assoc. disease (toxoplasma).
*Demyelination (e.g. [[multiple sclerosis]]).
*Resolving hematoma.

===Cyst with enhancing mural nodule===
*hemangioblastoma (#1 in adults)
*pilocytic astrocytoma (#1 in peds)
*pleomorphic xanthoastrocytoma
*ganglioglioma

==Grossing==
This is covered in the ''[[neuroanatomy]]'' article.

===Gross pathology===
The gross usually useless for arriving at a definitive diagnosis.

Exceptions:<ref>R. Kiehl. 8 November 2010.</ref>
*Sausage shape lesion of filum terminale = [[myxopapillary ependymoma]].
*Soft & tan colour = [[pituitary adenoma]].

==Normal histology==
{{main|Neurohistology}}
This is a big topic. It is covered in a separate article called ''[[neurohistology]]''.

==Histopathology==
===Neuronal changes===
====Anoxic neurons====
*[[AKA]] ''red neurons''.

Features:
*Intensely red cytoplasm.
*Pyknosis = nuclear shrinkage + darker staining.

=====Images=====
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons (WC)
Image:AcuteStroke_HE400x.jpg | Neurons in an acute stroke. (WC)
</gallery>
www:
*[http://neuropathology-web.org/chapter2/images2/2-anoxic.png Anoxic neurons (neuropathologyweb.org)].<ref>URL: [http://neuropathology-web.org/chapter2/chapter2aHIE.html http://neuropathology-web.org/chapter2/chapter2aHIE.html]. Accessed on: 10 December 2014.</ref>
*[http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-16.gif Anoxic neurons (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>

====Central chromatolysis====
Features:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html]. Accessed on: 22 December 2010.</ref>
*Central clearing.
**Nucleus and Nissl substance are pushed to cell periphery.

DDx:
*Axonal injury (traumatic).<ref name=pmid8909880>{{cite journal |author=Holland GR |title=Experimental trigeminal nerve injury |journal=Crit. Rev. Oral Biol. Med. |volume=7 |issue=3 |pages=237–58 |year=1996 |pmid=8909880 |doi= |url=}}</ref>
*Vitamin deficiency ([[pellagra]]).<ref name=pmid15577526>{{cite journal |author=Piercecchi-Marti MD, Pélissier-Alicot AL, Leonetti G, Tervé JP, Cianfarani F, Pellissier JF |title=Pellagra: a rare disease observed in a victim of mental and physical abuse |journal=Am J Forensic Med Pathol |volume=25 |issue=4 |pages=342–4 |year=2004 |month=December |pmid=15577526 |doi= |url=}}</ref>

=====Images=====
<gallery>
Image:Central_chromatolysis_-_intermed_mag_-_cropped.jpg | Central chromatolysis - intermed. mag. (WC)
Image:Central_chromatolysis_-_nf_-_very_high_mag.jpg | Central chromatolysis - NF stain - very high mag. (WC)
</gallery>
====Axonal swellings====
H&E:
*Eosinophilic (light pink) - ground glass-like appearance.
*Shape:
**Round if sectioned perpendicular to axis of axon.
***Bound by cell membrane.
***Large ~ typically 2-4x RBC diameter.
**Sausage-shaped if cut in along axis.

Images:
*[http://frontalcortex.com/gallery/pics/gliageek_VWMDx200.jpg Axonal swelling (frontalcortex.com)].<ref>URL: [http://frontalcortex.com/?page=oll&topic=24&qid=602 http://frontalcortex.com/?page=oll&topic=24&qid=602]. Accessed on: 3 November 2010.</ref>
*[http://www.neuropathologyweb.org/chapter3/images3/3-pvlaxonsweling.jpg Axonal swelling (neuropathologyweb.org)].

=====IHC=====
*APP.

Image:
*[http://vet.sagepub.com/content/37/6/677/F7.expansion.html Axonal swelling - APP (sagepub.com)].<ref>{{cite journal |author=Finnie JW, Manavis J, Blumbergs PC, Kuchel TR |title=Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin |journal=Vet. Pathol. |volume=37 |issue=6 |pages=677–80 |year=2000 |month=November |pmid=11105962 |doi= |url=http://vet.sagepub.com/content/37/6/677.full}}</ref>

===Glial changes===
====Astrocyte changes====
Reactive astrocytes:
*Approximately equally-spaced; distance between neighbouring astrocytes is ~2x (or more) the cell size.
*Well-defined cell border.
*Eosinophilic cytoplasm with many branching processes.
**Classically described as "funnel-shaped" in benign astrocytes.<ref>MUN. 15 November 2010.</ref>
*Peripheral nucleus.
<gallery>
Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg | Reactive astrocytes - high mag. (WC)
</gallery>

Alzheimer type II astrocyte:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 2 July 2010.</ref>
*Large cleared nucleus - '''key feature'''.
*Indistinct cytoplasm.
*Found in the context of ''hepatic encephalopathy'' in basal ganglia and lower layers of cortex.<ref name=Ref_Klatt202>{{Ref Klatt|202}}</ref>
*Images:
**[http://neuroquiz.com/?page=image&topic=1&qid=2714 Alzheimer type II astrocytes (neuroquiz.com)].
**[http://www.neuropathologyweb.org/chapter10/images10/10-AlzIIl.jpg Alzheimer type II astrocytes (neuropathologyweb.org)] .
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag.jpg| Alzheimer type II astrocytes. (WC)
</gallery>

Creutzfeldt cell:<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
*Finding associated with demyelinating disease.
*Image: [http://path.upmc.edu/cases/case336/images/fig03.jpg Crutzfeldt cell (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case336.html http://path.upmc.edu/cases/case336.html]. Accessed on: 15 January 2012.</ref>

Gemistocytic astrocytes:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 7 November 2010.</ref>
*Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:<ref name=Ref_MBNP173>{{Ref MBNP|173}}</ref>
*Cellular processes loaded with tau protein (as may be seen with tau [[IHC]] or Gallyas silver stain); Parisian-star-like appearance with special stain.
*+/-Multinucleated.
*A classic feature of ''[[progressive supranuclear palsy]]''.

====Other glial====
Bergmann gliosis (in the cerebellum):<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Thin layer of cells (2-3 cells) with open nuclei that are larger than granular cell layer nuclei; seen with Purkinje cell loss.

<gallery>
Image:Bergmann_gliosis_-_intermed_mag.jpg | Bergmann gliosis - intermed. mag. (WC)
Image:Bergmann_gliosis_-_high_mag.jpg | Bergmann gliosis - high mag. (WC)
Image:Metastatic_adenocarcinoma_-_cerebellum_-_intermed_mag.jpg | Bergmann gliosis due to compression by metastasis - intermed mag. (WC)
</gallery>
Image:
*[http://tpx.sagepub.com/content/35/5/676/F5.expansion.html Bergmann gliosis (sagepub.com)].

====Reactive change vs. malignancy====
Reactive changes vs. malignancy (mnemonic ''MIMICS''):<ref name=Ref_TPoSP254>{{Ref TPoSP|254}}</ref>
*'''MI'''crovesicular pattern.
*'''M'''itoses.
*'''I'''rregular spacing.
*'''C'''alcifications.
*'''S'''atellitosis, perineuronal.
**Large "crowds" of glial cells associated with nuclei.

===Inflammatory===
DDx:
*Autoimmune - [[Multiple sclerosis]].
*Neoplastic - [[Neuropathology tumours#CNS lymphoma|CNS lymphoma]].
*Infectious - [[HSV]].

====Encephalitis====
=====General=====
DDx:
*Viral encephalitis.
*Paraneoplastic syndromes.

=====Gross=====
*Frontal and temporal lobe - most common for HSV encephalitis.<ref>{{Ref APBR|416 Q47}}</ref>

=====Microscopic=====
Features:<ref name=pmid20051019>{{Cite journal | last1 = Takei | first1 = H. | last2 = Wilfong | first2 = A. | last3 = Malphrus | first3 = A. | last4 = Yoshor | first4 = D. | last5 = Hunter | first5 = JV. | last6 = Armstrong | first6 = DL. | last7 = Bhattacharjee | first7 = MB. | title = Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of the literature. | journal = Neuropathology | volume = 30 | issue = 4 | pages = 381-91 | month = Aug | year = 2010 | doi = 10.1111/j.1440-1789.2009.01079.x | PMID = 20051019 }}</ref>
*Perivascular inflammation.
*Microglia.
*+/-Neuronophagia.
**Phagocytosis of neurons.<ref>URL: [http://medical-dictionary.thefreedictionary.com/neuronophagia http://medical-dictionary.thefreedictionary.com/neuronophagia]. Accessed on: 11 April 2012.</ref>
*+/-Viral cytopathic changes.
*+/-Perineuronal inflammation.

Notes:
*Hemorrhage<ref name=pmid18246335>{{Cite journal | last1 = Vossough | first1 = A. | last2 = Zimmerman | first2 = RA. | last3 = Bilaniuk | first3 = LT. | last4 = Schwartz | first4 = EM. | title = Imaging findings of neonatal herpes simplex virus type 2 encephalitis. | journal = Neuroradiology | volume = 50 | issue = 4 | pages = 355-66 | month = Apr | year = 2008 | doi = 10.1007/s00234-007-0349-3 | PMID = 18246335 }}</ref> and necrosis - characteristic of HSV encephalitis.

Image:
*[http://neuropathology-web.org/chapter5/images5/5-21l.jpg HSV encephalitis (neuropathology-web.org)].<ref>URL: [http://neuropathology-web.org/chapter5/chapter5dViruses.html http://neuropathology-web.org/chapter5/chapter5dViruses.html]. Accessed on: 27 January 2012.</ref>

=====IHC=====
IHC stains for:
*Viral etiologies, e.g. [[HSV]], [[CMV]].
*Parasites, e.g. [[toxoplasma]].
*[[Fungi]], e.g. PASD.

===Architecture===
====Rosettes====
*Rosette = circular/flower-like arrangement of cells.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>

*Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**[[Ependymoma]].
**[[Medulloblastoma]], PNET.
**[[Central neurocytoma]].
**[[Glioblastoma]]s.

*Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**Medulloblastoma.
***Image: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Images/N1-TU-01-17.gif Medulloblastoma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17 http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17]. Accessed on: 3 December 2010.</ref>
**PNET (can be thought of as a supratentorial medulloblastoma) .

*Flexner-Wintersteiner rosette = rosette with empty centre (donut hole).<ref name=pmid16551982/>
**[[Retinoblastoma]]s.
**Pineoblastomas.
**Medulloepitheliomas.

*True ependymal rosette = surrounds a space.<ref name=pmid16551982/>
**[[Ependymoma]].

*Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
**Similar to Homer-Wright rosette.
**[[Pineocytoma]].
**[[Neurocytoma]].

====Other====
*Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
**Key feature: variable thickness; helps separate from RBCs.
**Well-seen on trichrome stains.
<gallery>
Image:Rosenthal_HE_40x.jpg | Rosenthal fibres. (WP)
Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear (WC/AFIP)
</gallery>
*Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.<ref>{{Ref MBNP|11}}</ref>
**Image: [Image:Pilocytic_Micro.jpg EGBs (WC/AFIP)].
*Pseudopalisading - picket fence-like alignment of cells; long axis of cells perpendicular to interface with other structures/cells.
**Pseudopalisading of tumour cells (around necrotic regions) is seen in [[glioblastoma]].

Note:
*Good set of articles: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=Neuropathology%20for%20the%20neuroradiologist Neuropathology for radiologists (ncbi.nlm.nih.gov)].

===Inclusion bodies===
*Negri bodies.
**Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
**[[Rabies]].
<gallery>
Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg | Negri bodies. (WC/CDC)
</gallery>

*Lewy bodies.
**Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.<ref name=pmid15235805>{{cite journal |author=Marui W, Iseki E, Kato M, Akatsu H, Kosaka K |title=Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease |journal=Acta Neuropathol. |volume=108 |issue=2 |pages=121–8 |year=2004 |month=August |pmid=15235805 |doi=10.1007/s00401-004-0869-4 |url=}}</ref>
<gallery>
Image:Lewy_Koerperchen.JPG | Lewy body. (WC)
</gallery>
====Table of inclusions====
{| class="wikitable sortable"
! Feature
! Appearance
! Associated disease
! Comment
! Image
|-
| Grumous bodies [[AKA]] granular bodies
| granular and eosinophilic ~50 micrometers
| neurodegenerative disease, neuroaxonal dystrophies, aging
| ?Comment
| ?Image
|-
| Cowdry type 1 AKA Cowdry type A
| eosinophilic & round + halo
| [[herpes simplex virus]]
| can be confused with Lewy body, Marinesco body
| ?Image
|-
| Lewy body
| round cytoplasmic eosinophilic body +/- pale halo
| [[Parkinson disease]], dementia with Lewy bodies
| morphology dependent on location in brain; +ve for alpha-synuclein, alpha-B crystallin, ubiquitin
| [[Image:Lewy_Koerperchen.JPG |thumb|center|150px|]], [http://firstaidteam.com/usmlerximages/v/USMLERxLewy+bodies.gif.html]
|-
| Lafora body
| round
| myoclonic [[epilepsy]]
| look like corpora amylacea; location: dentate nucleus, liver, skeletal muscle, sweat glands
| ?Image
|-
| Lipofuscin
| yellow & granular
| aging
| olive, dendate
| ?Image
|-
| Negri body
| small eosinophic bodies
| rabies
| found in hippocampal neurons and Purkinje cells
| [[Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg|thumb|center|150px|]]
|-
| Hirano body
| concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron
| Alzheimer disease, Pick disease<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| actin crystals, may look like capillaries; location: CA1 of hippocampus
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adhirano.jpg]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>
|-
| Neurofibrillary tangles
| flame-shaped cytoplasmic thingy ~30 micrometers
| aging, Alzheimer's disease
| seen with silver stain
| [http://www.pakmed.net/academic/age/alz/plaques_tanglesBorder.jpg Schematic]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>, [http://faculty.washington.edu/alexbert/MEDEX/Fall/adtangle.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Granulovacuolar degeneration
| cytoplasmic vacuoles 4-5 micrometers
| ageing, [[Alzheimer's disease]], Pick's disease
| main found in Ammon horn<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adgvd.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Pick bodies
| round, homogenous, intracytoplasmic, ~10 micrometers
| [[Pick's disease]]
| pyramidal neurons, dentate granule cells (hippocampus); +ve for tau, tubulin, ubiquitin
| [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?action=view&current=Picks60x.jpg&mediafilter=images]
|-
| Bunina body
| size of Nissl granules, eosinophilic
| [[amyotrophic lateral sclerosis]] (ALS)
| EM: membrane-bound bodies; ubiquitin +ve
| [http://pathol.umin.ac.jp/gakubu/exam/2006jpg/19.jpg]
|-

|}

Image collection: [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?mediafilter=images Inclusion bodies (photobucket.com)].

==Immunohistochemistry==
{{Main|Immunohistochemistry}}
===General===
*S-100.
**Sensitive... but non-specific, e.g. also stains [[melanoma]].

===Glial===
*GFAP (glial fibrillary acidic protein) - should stain perikaryon.

====Glial tumours====
Standard work-up:
*GFAP.
*p53.
*Ki-67.

===Neuronal===
*Synaptophysin.
*Chromogranin.

===Carcinoma vs. glial tumours===
*AE1/AE3 often +ve in glial tumours (e.g. astrocytomas, oligodendrogliomas); CAM5.2 is usu. -ve in glial tumours.<ref name=Ref_PSNP_12>{{Ref PSNP|12}}</ref>

===Others===
*APP (amyloid precursor protein) - detects axonal swellings.
*NF (neurofilament) - detects axonal swellings.

=Brain tumours=
{{main|Neuropathology tumours}}
Tumours are a big part of neuropathology. The most common brain tumour is a metastasis. The most common primary tumour (in adults) is glioblastoma which has a horrible prognosis.

=Non-tumour=
==Cerebral hemorrhage==
:See: ''[[Intracranial hematoma]]'' for intracranial bleeds

Includes discussion of:
*[[Epidural hematoma]].
*[[Subdural hematoma]].
*[[Subarachnoid hematoma]].
*[[Intracerebral hematoma]]s.

==Duret hematoma==
*[[AKA]] Duret hemorrhage.
===General===
*Bleed in the upper brainstem (midbrain and pons).
**Thought to be due to transtentorial herniation secondary to supratentorial mass effect (e.g. supratentorial tumour, [[intracranial hemorrhage]]).<ref name=pmid11819006>{{Cite journal | last1 = Parizel | first1 = PM. | last2 = Makkat | first2 = S. | last3 = Jorens | first3 = PG. | last4 = Ozsarlak | first4 = O. | last5 = Cras | first5 = P. | last6 = Van Goethem | first6 = JW. | last7 = van den Hauwe | first7 = L. | last8 = Verlooy | first8 = J. | last9 = De Schepper | first9 = AM. | title = Brainstem hemorrhage in descending transtentorial herniation (Duret hemorrhage). | journal = Intensive Care Med | volume = 28 | issue = 1 | pages = 85-8 | month = Jan | year = 2002 | doi = 10.1007/s00134-001-1160-y | PMID = 11819006 }}</ref>
*Often fatal.<ref name=pmid11098635>{{Cite journal | last1 = Fujimoto | first1 = Y. | last2 = Aguiar | first2 = PH. | last3 = Freitas | first3 = AB. | last4 = de Andrade | first4 = AF. | last5 = Marino Júnior | first5 = R. | title = Recovery from Duret hemorrhage: a rare complication after craniotomy--case report. | journal = Neurol Med Chir (Tokyo) | volume = 40 | issue = 10 | pages = 508-10 | month = Oct | year = 2000 | doi = | PMID = 11098635 }}</ref>
===Gross===
*Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).<ref name=pmid11819006/>

Image:
*[http://library.med.utah.edu/WebPath/jpeg5/CNS037.jpg Duret hemorrhage (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html]. Accessed on: 4 December 2011.</ref>

===Microscopic===
Features:
*RBC extravasation.
*+/-Hemosiderin-laden macrophages.
*+/-Ischemic neurons.

==Alcohol & CNS==
===Clinical===
*Wernicke's encephalopathy
**Mnemonic ''WACO'':
***Wernicke's.
***Ataxia.
***Confusion, confabulation -- Korsakoff.
***Ocular Sx (CN IV palsy).
**Cause: thiamine deficiency.

===Pathology===
Features:<ref>http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract</ref>
*Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex<ref>URL: [http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939 http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939]. Accessed on: 22 September 2010.</ref> usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>
*Central pontine myelinolysis (CPM).<ref name=pmid21085565>{{cite journal |author=Campbell MC |title=Hyponatremia and central pontine myelinolysis as a result of beer potomania: a case report |journal=Prim Care Companion J Clin Psychiatry |volume=12 |issue=4 |pages= |year=2010 |pmid=21085565 |pmc=2983455 |doi=10.4088/PCC.09l00936ecr |url=}}</ref>
**Just what it sound like - myelin loss in the central pons.
**Classically associated with rapid correction of hyponatremia.<ref>{{cite journal |author=Bernsen HJ, Prick MJ |title=Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia |journal=Acta Neurol Belg |volume=99 |issue=3 |pages=189–93 |year=1999 |month=September |pmid=10544728 |doi= |url=}}</ref>
*Mammillary body shrinkage.<ref name=pmid8947329>{{cite journal |author=Shear PK, Sullivan EV, Lane B, Pfefferbaum A |title=Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia |journal=Alcohol. Clin. Exp. Res. |volume=20 |issue=8 |pages=1489-95 |year=1996 |month=November |pmid=8947329 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=1996&volume=20&issue=8&spage=1489}}</ref>
*Anterior cerebellar vermis atrophy; weak finding - as also age-related.<ref name=pmid3478969>{{cite journal |author=Torvik A |title=Brain lesions in alcoholics: neuropathological observations |journal=Acta Med. Scand. Suppl. |volume=717 |issue= |pages=47–54 |year=1987 |pmid=3478969 |doi= |url=}}</ref>
**Vermis atrophy is also seen in schizophrenia.<ref name=pmid1938163>{{cite journal |author=Sandyk R, Kay SR, Merriam AE |title=Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia |journal=Int. J. Neurosci. |volume=57 |issue=3-4 |pages=205–12 |year=1991 |month=April |pmid=1938163 |doi= |url=}}</ref>

====Marchiafava-Bignami Disease====
*Rare.
*Demyelination of the corpus callosum.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>

====Wernicke's encephalopathy====
General:
*Due to thiamine deficiency.
**Malnourishment often accompanies [[alcoholism]].

Features:<ref name=pmid3929155>{{Cite journal | last1 = Torvik | first1 = A. | title = Two types of brain lesions in Wernicke's encephalopathy. | journal = Neuropathol Appl Neurobiol | volume = 11 | issue = 3 | pages = 179-90 | month = | year = | doi = | PMID = 3929155 }}</ref>
*Neurons of mammillary bodies preserved - '''key'''.
*Loss of myelin.
*Hemorrhage.
*Edema.
*Reactive blood vessels.

Note:
*The thalamus and inferior olives show neuronal loss.<ref name=pmid3929155/>

====Common non-specific findings====
*[[Intracranial haemorrhage]] - due to trauma.

==Meningitis==
===General===
*Definition: inflammation of the meninges (pia mater, arachnoid membranes, dura mater).

Classic clinical presentation:
*Neck stiffness.
*Fever.
*+/-Headache.
*+/-Decreased level of consciousness.

CSF findings:
{| class="wikitable sortable"
! Type
! Glucose
! Protein
! Cells
|-
| Bacterial, acute
| low
| high
| neutrophils
|-
| Viral
| normal
| slight elevation
| lymphocytes
|}

====Etiology====
*Infectious.
**Bacterial.
**Viral.
**Parasitic
*Autoimmune.
*Toxic.
*Aseptic - see ''[[Mollaret's meningitis]]''.

Bacterial meningitis - most probably cause by age:<ref>{{Ref PCPBoD8|666-7}}</ref>
{| class="wikitable sortable"
! Age
! Organism
|-
| Neonate
| ''Escherichia coli'', Group B Streptococcus
|-
| Infants, children
| ''Streptococcus pneumoniae''
|-
| Adolescents, young adults
| ''Neisseria meningitidis''
|-
| Elderly
| ''Streptococcus pneumoniae'', ''Listeria monocytogenes''
|}

===Gross===
Features:
*+/-Clouded appearance of the meninges.
*+/-Pus.
*+/-Petechiae.
*+/-Cerebral edema.

====Image====
<gallery>
Image:Streptococcus_pneumoniae_meningitis,_gross_pathology_33_lores.jpg | Meningitis. (WC)
</gallery>

===Microscopic===
Features:
*Inflammation of the meninges:
**+/-[[Neutrophil]]s.
**+/-Lymphocytes.
**+/-[[Plasma cell]]s.
*+/-Microorganisms (infectious meningitis):
**Bacteria.
**[[Fungi]], e.g. [[aspergillosis]] (may be intravascular).

Main DDx:
*[[Lymphoma]].

====Image====
<gallery>
Image:Meningitis_Histopathology.jpg | Bacterial meningitis. (WC)
</gallery>

==Cerebral abscess==
===General===
*May mimic malignancy clinically.

===Microscopic===
Features:
*Sheets of neutrophils surrounded by fibrosing brain.
**Fibrosing brain: pale (lighter pink than normal brain tissue), dense.

Images:
*[http://pathology.class.kmu.edu.tw/ch01/4-1.jpg Cerebral abscess - very low mag. (kmu.edu.tw)].<ref>URL: [http://pathology.class.kmu.edu.tw/ch01/Slide4.htm http://pathology.class.kmu.edu.tw/ch01/Slide4.htm]. Accessed on: 1 January 2012.</ref>
*[http://pathology.class.kmu.edu.tw/ch01/4-5.jpg Cerebral abscess - low mag. (kmu.edu.tw)].

==Neurodegenerative diseases==
{{Main|Neurodegenerative diseases}}
This is a hueueuge topic. It is covered in its own article and includes a general discussion of dementia.

==Epilepsy==
{{Main|Epilepsy}}

==Cerebrovascular accident==
*Abbreviated ''CVA''.
*[[AKA]] ''stroke''.
{{Main|Cerebrovascular accident}}

==Hypoxic-ischemic encephalopathy==
*Abbreviated ''HIE''.
{{Main|Hypoxic-ischemic encephalopathy}}

==Multiple sclerosis==
*Abbreviated ''MS''.
{{Main|Multiple sclerosis}}

==Cerebral amyloid angiopathy==
===General===
*Abbreviated ''CAA''.
*Disease of the old.
*Strong association with ''[[lobar haemorrhage]]'' (bleeds of the cerebellar cortex and cerebral cortex).<ref name=pmid16982664>{{cite journal |author=Thanvi B, Robinson T |title=Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage in older people |journal=Age Ageing |volume=35 |issue=6 |pages=565–71 |year=2006 |month=November |pmid=16982664 |doi=10.1093/ageing/afl108 |url=}}</ref>

Etiology:
*[[Amyloid]] deposition in the basal lamina of smooth muscle (in the cerebellar cortex and cerebral cortex).

===Gross===
*Bleeds typically superficial (cortex and subcortical white matter) and in the frontal lobe or parietal lobe.<ref name=pmid17297004>{{Cite journal | last1 = Haacke | first1 = EM. | last2 = DelProposto | first2 = ZS. | last3 = Chaturvedi | first3 = S. | last4 = Sehgal | first4 = V. | last5 = Tenzer | first5 = M. | last6 = Neelavalli | first6 = J. | last7 = Kido | first7 = D. | title = Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging. | journal = AJNR Am J Neuroradiol | volume = 28 | issue = 2 | pages = 316-7 | month = Feb | year = 2007 | doi = | PMID = 17297004 | URL = http://www.ajnr.org/content/28/2/316.long }}</ref>

===Microscopic===
Features:
*Amorphous, acellular eosinophilic material within walls of small arteries.
**This is a high power diagnosis with congo red staining.

Notes:
*Amyloidosis is seen in all individuals with [[Alzheimer's disease]]; the amount of amyloid is what differs -- in CAA it is lots and lots.
*The white matter is typically spared by CAA.<ref name=pmid19225408>{{Cite journal | last1 = Schröder | first1 = R. | last2 = Deckert | first2 = M. | last3 = Linke | first3 = RP. | title = Novel isolated cerebral ALlambda amyloid angiopathy with widespread subcortical distribution and leukoencephalopathy due to atypical monoclonal plasma cell proliferation, and terminal systemic gammopathy. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 3 | pages = 286-99 | month = Mar | year = 2009 | doi = 10.1097/NEN.0b013e31819a87f9 | PMID = 19225408 }}
</ref>

====Images====
<gallery>
Image:Cerebral_amyloid_angiopathy_-_very_high_mag.jpg |CAA - congo red - very high mag. (WC)
Image:Cerebral_amyloid_angiopathy_-_low_mag.jpg |CAA - congo red - low mag. (WC)
Image:Cerebral_amyloid_angiopathy_-2b-_amyloid_beta_-_high_mag.jpg |CAA - beta-amyloid - high mag. (WC)
</gallery>
===Stains===
*[[Congo red]].

===IHC===
*Abeta-amyloid (AKA beta-amyloid).

==Central pontine myelinolysis==
*Abbreviated ''CPM''.
*[[AKA]] ''pontine myelinolysis''.
===General===
*Classically in the pons, ergo "pontine" is in the name.
*Classically midline, ergo "central" is in the name.
**May occur elsewhere -- known as ''extrapontine myelinolysis''.

Etiology:
*Rapid correction of hyponatremia.<ref name=pmid22080394>{{Cite journal | last1 = Chang | first1 = Y. | last2 = An | first2 = DH. | last3 = Xing | first3 = Y. | last4 = Qi | first4 = X. | title = Central pontine and extrapontine myelinolysis associated with acute hepatic dysfunction. | journal = Neurol Sci | volume = | issue = | pages = | month = Nov | year = 2011 | doi = 10.1007/s10072-011-0838-3 | PMID = 22080394 }}</ref>
*Tacrolimus post-liver transplant.<ref name=pmid21959523>{{Cite journal | last1 = Fukazawa | first1 = K. | last2 = Nishida | first2 = S. | last3 = Aguina | first3 = L. | last4 = Pretto | first4 = E. | title = Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation. | journal = Ann Transplant | volume = 16 | issue = 3 | pages = 139-42 | month = Sep | year = 2011 | doi = | PMID = 21959523 }}</ref>
*Associated with [[alcoholism]] and malnourishment.

Clinical:<ref>{{Cite journal | last1 = Lai | first1 = CC. | last2 = Tan | first2 = CK. | last3 = Lin | first3 = SH. | last4 = Chen | first4 = HW. | title = Central pontine myelinolysis. | journal = CMAJ | volume = 183 | issue = 9 | pages = E605 | month = Jun | year = 2011 | doi = 10.1503/cmaj.090186 | PMID = 21543311 | PMC = 3114939 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114939/?tool=pubmed }}</ref>
*Decreased level of consciousness - most common.
*Quadriplegia.
*Poor prognosis.

===Microscopic===
Features:<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*Myelin loss.
*No inflammation.
*Relative preservation of neurons.

Images:
*[http://neuropathology-web.org/chapter6/images6/6-9l.jpg CPM (neuropathology-web.org)].<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*[http://dartmed.dartmouth.edu/spring09/html/virtual_microscopy_we/ CPM (dartmouth.edu)].

==Vascular malformations==
{{Main|Vascular malformations}}
Types:<ref name=pmid17076525>{{cite journal |author=Prayson RA, Kleinschmidt-DeMasters BK |title=An algorithmic approach to the brain biopsy--part II |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1639–48 |year=2006 |month=November |pmid=17076525 |doi= |url=}}</ref>
#Arteriovenous malformation.
#*Most important clinically - highest risk of bleeding.
#Varix.
#*One large (dilated) vein.
#Venous angioma.
#*Many small veins.
#Cavernous malformation.
#*Vessels are back-to-back (no intervening parenchyma).

Also see: ''[[Sturge-Weber syndrome]]''.

=Cysts=
===General===
*All are "benign", but some may be fatal due to spatial constraints.

===List of cysts===
*[[Colloid cyst]].
**Columnar epithelium.
*Arachnoid cyst - considered precursor of [[meningioma]].
**[[Psammoma bodies]].
**Clumps of cells.
**Whorled pattern.
*[[Dermoid cyst]].
**Skin + adnexal structures.
**... think of ovarian dermoid.
*Epidermoid cyst.
*Choroid plexus cyst.
*Neuroenteric cyst.
**Foregut cyst with connection to dura.<ref>URL: [http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm]. Accessed on: 19 December 2011.</ref>
***Gastrointestinal tract epithelium.
***Usually seen with vertebral anomalies.
*Epithelial cyst.
*Others.

==Colloid cyst==
===General===
Classic presentation:<ref name=pmid15228889>{{Cite journal | last1 = Spears | first1 = RC. | title = Colloid cyst headache. | journal = Curr Pain Headache Rep | volume = 8 | issue = 4 | pages = 297-300 | month = Aug | year = 2004 | doi = | PMID = 15228889 }}</ref>
*Headache - may be relieved by lying down.
*Can cause [[sudden natural death]].<ref name=pmid14716130>{{Cite journal | last1 = Kava | first1 = MP. | last2 = Tullu | first2 = MS. | last3 = Deshmukh | first3 = CT. | last4 = Shenoy | first4 = A. | title = Colloid cyst of the third ventricle: a cause of sudden death in a child. | journal = Indian J Cancer | volume = 40 | issue = 1 | pages = 31-3 | month = | year = | doi = | PMID = 14716130 }}</ref>

===Gross===
*Fluid filled cyst - classically in the third ventricle.

====Images====
<gallery>
Image:Human brain showning a colloid cyst in the third ventricle.jpg| Colloid cyst at autopsy. (Shaktawat ''et al.''<ref name=pmid16867192>{{Cite journal | last1 = Shaktawat | first1 = SS. | last2 = Salman | first2 = WD. | last3 = Twaij | first3 = Z. | last4 = Al-Dawoud | first4 = A. | title = Unexpected death after headache due to a colloid cyst of the third ventricle. | journal = World J Surg Oncol | volume = 4 | issue = | pages = 47 | month = | year = 2006 | doi = 10.1186/1477-7819-4-47 | PMID = 16867192 }}</ref>)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F3.expansion.html Colloid cyst of third ventricle (ajnr.org)].<ref name=pmid11003281/>

===Microscopic===
Features:<ref name=pmid11003281>{{Cite journal | last1 = Armao | first1 = D. | last2 = Castillo | first2 = M. | last3 = Chen | first3 = H. | last4 = Kwock | first4 = L. | title = Colloid cyst of the third ventricle: imaging-pathologic correlation. | journal = AJNR Am J Neuroradiol | volume = 21 | issue = 8 | pages = 1470-7 | month = Sep | year = 2000 | doi = | PMID = 11003281 }}</ref>
*Simple epithelium with ciliated cells and goblet cells.

====Images====
<gallery>
Image:Colloid_Cyst_HE_40x.jpg | Colloid cyst. (WC)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F4.expansion.html Colloid cyst (ajnr.org)].<ref name=pmid11003281/>

=Paediatric pathology=
==Kernicterus==
===General===
*Due to hyperbilirubinemia.<ref name=pmid7063283>{{Cite journal | last1 = Turkel | first1 = SB. | last2 = Miller | first2 = CA. | last3 = Guttenberg | first3 = ME. | last4 = Moynes | first4 = DR. | last5 = Godgman | first5 = JE. | title = A clinical pathologic reappraisal of kernicterus. | journal = Pediatrics | volume = 69 | issue = 3 | pages = 267-72 | month = Mar | year = 1982 | doi = | PMID = 7063283 }}</ref>

===Gross===
*Yellow staining:<ref name=npw>URL: [http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html]. Accessed on: 30 May 2012.</ref>
**Basal ganglia.<ref name=pmid10920171>{{Cite journal | last1 = Hansen | first1 = TW. | last2 = Hervieux | first2 = JF. | last3 = Orth | first3 = J. | last4 = Schmorl | first4 = CG. | last5 = Baumes | first5 = JB. | title = Pioneers in the scientific study of neonatal jaundice and kernicterus. | journal = Pediatrics | volume = 106 | issue = 2 | pages = E15 | month = Aug | year = 2000 | doi = | PMID = 10920171 }}</ref>
**Hippocampus.<ref name=pmid15091133>{{Cite journal | last1 = Paksoy | first1 = Y. | last2 = Koç | first2 = H. | last3 = Genç | first3 = BO. | title = Bilateral mesial temporal sclerosis and kernicterus. | journal = J Comput Assist Tomogr | volume = 28 | issue = 2 | pages = 269-72 | month = | year = | doi = | PMID = 15091133 }}</ref>
**Subthalamic nucleus.

Note:
*May not be specific.<ref name=pmid7063283/>

Image:
*[http://www.flickr.com/photos/neonatal-box/6275988844/ Kernicterus (flickr.com)].

===Microscopic===
Features - similar to [[HIE]]:<ref name=npw/>
*+/-Red neurons.
*+/-Gliosis.

==Joubert syndrome==
*Malformation of the cerebellar vermis.<ref name=ninds_joubert>[http://www.ninds.nih.gov/disorders/joubert/joubert.htm http://www.ninds.nih.gov/disorders/joubert/joubert.htm]</ref>

===Epidemiology===
*Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.<ref name=ninds_joubert/>

=Weird stuff=
==Acute disseminated encephalomyelitis==
*Abbreviated ''ADEM''.
{{Main|Acute disseminated encephalomyelitis}}

==Neuromyelitis optica==
*Abbreviated ''NMO''.
===General===
*Rare autoimmune disease - once considered a variant of [[multiple sclerosis]].
**Autoantibodies directed at aquaporin-4.<ref name=pmid22087205>{{Cite journal | last1 = Kim | first1 = W. | last2 = Kim | first2 = SH. | last3 = Kim | first3 = HJ. | title = New insights into neuromyelitis optica. | journal = J Clin Neurol | volume = 7 | issue = 3 | pages = 115-27 | month = Sep | year = 2011 | doi = 10.3988/jcn.2011.7.3.115 | PMID = 22087205 }}</ref>

Diagnosis:
*NMO-IgG.

Clinical - preferentially:
*Eye (optic neuritis).
*Spinal cord (myelitis).

===Microscopic===
Features:
*Inflammation - lymphocytes, macrophages.
*Reactive astrocytes.

Images:
*[http://path.upmc.edu/cases/case637.html Neuromyelitis optica - several images (upmc.edu)].

===IHC===
*Mixed lymphocyte population with CD3 > CD20.
*Aquaporin-4 loss.

==Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy==
*Commonly abbreviated ''CADASIL''.
{{Main|Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy}}

==Progressive multifocal leukoencephalopathy==
*Abbreviated ''PML''.
{{Main|Progressive multifocal leukoencephalopathy}}

=See also=
*[[Brain tumours]].
*[[Pituitary gland]].
*[[Histiocytoses]].
*[[Intracranial hematomas]].
*[[Spine]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
**[http://www.neuropathologyweb.org/test6/6test.html Quiz (neuropathologyweb.org)].
*[http://blog.lib.umn.edu/santa013/neuropathology/ Neuropathology cases (lib.umn.edu)].
*[http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 Neuropathology micrographs - identifying the site (stonybrookmedicalcenter.org)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/AAQuestion-41-60.htm Neurocytopathology quiz (ouhsc.edu)].
*[http://wiki.cns.org/wiki/index.php/Main_Page WikiCNS (wiki.cns.org)].

[[Category:Neuropathology]]