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'''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.
[[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]].


This article is an introduction to neuropathology.  There are separate articles for [[brain tumours]], the [[pituitary gland]] and [[muscle pathologies]].
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.


==Gross==
==Neuroanatomy==
*Uncus (as in ''uncal herniation'').
{{Main|Neuroanatomy}}
*Cerebellar tonsils (as in ''tonsillar herniation'').
This is a large topic. It covered in a separate article, that also covers grossing.


*Longitudinal fissure - divides cerebrum into hemispheres.
==Neuroradiology==
*Central sulcus - separate ''parietal lobe'' from ''frontal lobe''.
Key factors to consider in evaluation:
*Lateral sulcus (Sylvian fissure, lateral fissure) - separates temporal lobe from frontal lobe & parietal lobe.
# Location.
# Number of lesions - single versus multiple.
# Cystic versus solid lesion.
# Enhancement.


===Less important===
==Lesion location==
*Glomeruli of Arnold.
In neuroradiology and neuropathology, real estate is crucial. Lesion location can often narrow your differential.
**Over lies hippocampus.


*Calcarine cortex - occipital lobe
Cortical lesions (gray matter):
**Line of Gennari -- very thin white line in the grey matter.
* [[Oligodendroglioma]].
**Image: [http://library.med.utah.edu/WebPath/HISTHTML/NEURANAT/CNS227A.html Calcarine cortex (med.utah.edu)] as part of [http://www.gfmer.ch/selected_images_v2/detail_list.php?offset=15&cat1=3&cat2=13&cat3=0&cat4=2&stype=n CNS collection (gfmer.ch)].
* [[DNET]].
* [[Ganglioglioma]].
* [[Pleomorphic xanthoastrocytoma]].
* Extraventricular [[ependymoma]].


===Vascular structures===
Cortical-subcortical junction:
*Posterior cerebellar arteries.
* [[brain metastasis|Metastases]].
**Inferior of ''posterior cerebral arteries''.
* Abscesses (hematogenous spread).
*Anterior inferior cerebellar arteries.
**Branch off ''basilar artery''.
*Posterior inferior cerebellar arteries - [[AKA]] ''PICA''.
**Branch off ''vertebral arteries''.


Images:
Subcortical lesions (white matter):
*[http://en.wikipedia.org/wiki/File:Circle_of_Willis_en.svg Circle of Willis (WP)] .
* [[Glioblastoma]].
*[http://library.med.utah.edu/WebPath/HISTHTML/NEURANAT/CNS334A.html Interactive schematic (utah.edu)].
* Diffuse gliomas.
* Demyelinating plaques.
 
Deep gray matter lesions (e.g. basal ganglia):
* Gliomas.
* [[Hypertensive hemorrhage]]
 
Cerebellar lesions:
* [[Medulloblastoma]].
* [[Pilocytic astrocytoma]].
* [[AT/RT]].


==Normal histology==
Intraventricular lesions:
===Normal cells===
* [[Ependymoma]].
*Neuron:
* [[Subependymoma]].
**Abundant cytoplasm - '''key feature'''.
* [[Pilocytic astrocytoma]].
**Often very large cells, with angled edges.
* [[Central neurocytoma]].
**Prominent nucleolus.
* Rosette forming glioneuronal tumour of the fourth ventricle.
**Nissl substance (granular perinuclear material - rough ER).
*Glial cells.
**Oligodendrocyte.
***Small round nuclei (lymphocyte-like nucleus) - '''key feature'''.
***May resemble a ''fried egg'' on H&E (clear cytoplasm, central nucleus).
**Astrocyte.
***Irregular non-ovoid nucleus - '''key feature'''.
***Nuclei less dense than in oligodendrocyte.
***Close to blood vessels.
***Form blood-brain barrier.
***Cytoplasm normally ''not'' visible.
***Image: [http://embryology.med.unsw.edu.au/histology/endocrine/pin42he.jpg astrocyte (med.unsw.edu.au)] (in [http://embryology.med.unsw.edu.au/notes/endocrine12.htm endocrine development]).
**Microglia - macrophage of the brain (derived from monocyte).
***May be large.
***May have vesicles.
***Rarely seen in normal tissue.
*Ependyma.
**Simple ciliated cuboidal epithelium.
**Image: [http://www.stonybrookmedicalcenter.org/sbumcfiles/images/221-001.jpg Ependyma (stonybrookmedicalcenter.org)].


====Normal cellular constituents in a table====
Suprasellar (above the pituitary):
{| class="wikitable"
* [[Craniopharyngioma]].
|
* [[Germinoma]].
|Key feature
* [[Pilomyxoid astrocytoma]].
|Other features
|Image
|-
|Neuron
| cytoplasm
| Nissl substance<br> (prominent RER), "sharp" corners <br>in cell membrane
| [http://commons.wikimedia.org/wiki/File:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg red neurons (WC)]
|-
|Astrocyte
| non-ovoid nucleus
| no cytoplasm
| [http://embryology.med.unsw.edu.au/histology/endocrine/pin42he.jpg (unsw.edu)]
|-
|Oligodendrocyte
| round small nucleus
| peri-nuclear clearing
|
|-
|Microglia
| rod-like shape,<br> may have "bent" nucleus
| rarely seen in normal tissue
| [http://missinglink.ucsf.edu/lm/ids_104_cns_injury/Response%20_to_Injury/Microglia.htm (ucsf.edu)],[http://www.pathology.vcu.edu/WirSelfInst/neuro_medStudents/glialpath.html (vcu.edu)]
|-
|}


====Neurons====
==Number of lesions==
There are many types of 'em.  Broadly, they can be classified as:
If ''single'' lesion = think primary, neoplastic
#Pyramidal - have a pyramidal shape.
If ''multiple'' lesions = think metastatic, neoplastic or infectious
##Dentrites go to molecular layer.
'''NB: glioblastoma can be multifocal''' (and the foci can be quite far apart)
##Axons go to outside of cortex.
#Non-pyramidal.


Motor neurons:
==Cystic vs. solid lesions==
*Coarse Nissl substance - '''key feature'''.
Some tumours are classically cystic with a small solid component (so-called cyst with a mural nodule) -- e.g. pilocytic astrocytoma, ganglioglioma, hemangioblastoma
**Nissl described as having a ''tigroid appearance''.<ref>URL: [http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1]. Accessed on: 5 July 2010.</ref>
*Polygonal shape.
*Send dendrites in all directions.


Image: [http://www.stonybrookmedicalcenter.org/sbumcfiles/images/238-002.jpg Motor neuron (stonybrookmedicalcenter.org)].
==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.


===Histology - where===
===Ring enhancing lesions===
====Subependyma====
In [[HIV]]/AIDS patients... mass on CT if infection:
Features:<ref>Half-day. 28 June 2010.</ref>
*[[Toxoplasmosis]] - most common.<ref>MUN. Feb 3, 2009.</ref>
*Ependyma (simple ciliated cuboidal epithelium).
*Subependymal plate - connective tissue with blood vessels.


====Pons====
Ring enhancing lesion (DDx) - mnemonic ''MAGICAL DR'':<ref>{{Ref TN2005 |NS7}}</ref>
Features:
*Metstasis.
*Looks like bacon.<ref>Half-day. 28 June 2010.</ref>
*Abscess.
*Image: [http://www.stonybrookmedicalcenter.org/sbumcfiles/images/243-scout.jpg Pons (stonybrookmedicalcenter.org)].
*[[Glioblastoma]].
*[[Infarct]].
*Contusion.
*AIDS-related.
*[[Lymphoma]] + [[HIV]] assoc. disease (toxoplasma).
*Demyelination (e.g. [[multiple sclerosis]]).
*Resolving hematoma.


====Caudate====
===Cyst with enhancing mural nodule===
Features:
*hemangioblastoma (#1 in adults)
*Neurons with adjacent ependymal lining.<ref>URL: [http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1]. Accessed on: 2 July 2010.</ref>
*pilocytic astrocytoma (#1 in peds)
**The caudate forms lateral wall of lateral ventricle.
*pleomorphic xanthoastrocytoma
*ganglioglioma


====Putamen====
==Grossing==
Features:
This is covered in the ''[[neuroanatomy]]'' article.
*Histologically identical to the ''caudate'' - but not adjacent to a ventricle, i.e. an ependymal lining.
*Striatopallidal fibers [[AKA]] ''pencils of Wilson'' - bundles of blue fibres (on H&E LFB).
**Image: [http://frontalcortex.com/?page=oll&topic=24&qid=760 Pencils of Wilson (frontalcortex.com)].


====Globus pallidus====
===Gross pathology===
Features:
The gross usually useless for arriving at a definitive diagnosis.  
*Histologically distinct from caudate and putamen.


====Hippocampus====
Exceptions:<ref>R. Kiehl. 8 November 2010.</ref>
Hippocampal formation:<ref>URL: [http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1]. Accessed on: 2 July 2010.</ref>
*Sausage shape lesion of filum terminale = [[myxopapillary ependymoma]].
#Dentate gyrus.
*Soft & tan colour = [[pituitary adenoma]].
#*"Dense" thin layer of nuclei.
#*Quasi "U-shaped"; "open" (top) portion of "U" is superolateral.
#*Image: [http://www.stonybrookmedicalcenter.org/sbumcfiles/images/225-001.jpg Dentate gyrus (stonybrookmedicalcenter.org)].
#Hippocampus proper ([[AKA]] ''Ammon's horn'') - this is subdivided:
#*CA3 - superior.
#*CA1 - inferior (next to subiculum).
#*CA2 - in between CA3 and CA1, lateral.
#*CA4 - medial (closest to dentate gyrus; CA4 sits in "open" part of "U").
#Subicular complex.


Images:
==Normal histology==
*[http://en.wikipedia.org/wiki/File:Brainmaps-macaque-hippocampus.jpg Hippocampus - frontal section (WP)].
{{main|Neurohistology}}
*[http://commons.wikimedia.org/wiki/File:Hippocampus_%28brain%29.jpg Hippocampus - good schematic (WC)].
This is a big topic. It is covered in a separate article called ''[[neurohistology]]''.
*[http://www.ajnr.org/cgi/content-nw/full/28/5/958/F1 Hippocampus (ajnr.org)].
*[http://edoc.hu-berlin.de/dissertationen/schubert-stephan-nicolas-2003-09-26/HTML/schubert_html_21d219b1.png Hippocampus and subiculum (hu-berlin.de)].
*[http://spinwarp.ucsd.edu/NeuroWeb/Text/br-800epi/br-800epi1.gif Hippocampus - crappy schematic (ucsd.edu)].


Important note:
==Histopathology==
*CA1 - weak link, dies in ischemia, affected by hypoglycemia.
===Neuronal changes===
*CA2 - resistant to ischemia.
====Anoxic neurons====
*[[AKA]] ''red neurons''.


DDx of ischemia-like changes in the hippocampus:
Features:
*Toxins.
*Intensely red cytoplasm.
*Pyknosis = nuclear shrinkage + darker staining.  


====Cerebellum====
=====Images=====
Main components:
<gallery>
*Cortex (superficial) - branches (Christmas tree-like).
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons (WC)
*Dentate nucleus (deep) - looks like the bite impression of a molar.
Image:AcuteStroke_HE400x.jpg | Neurons in an acute stroke. (WC)
**Image: [http://www.stonybrookmedicalcenter.org/sbumcfiles/images/227-scout.jpg Cerebellum, cortex & dendate nucleus - low power (stonybrookmedicalcenter.org)].
</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>


Cerebellar cortex:
====Central chromatolysis====
*Layers (superficial to deep) - mnemonic ''MPG'':<ref>URL: [http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1]. Accessed on: 2 July 2010.</ref>
Features:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html]. Accessed on: 22 December 2010.</ref>
*#Molecular layer -- "very pink" on H&E.
*Central clearing.
*#*Inhibitory interneurons: stellate cells, basket cells.
**Nucleus and Nissl substance are pushed to cell periphery.
*#Purkinje cell layer.
*#*One cell layer thick - hueuege cells.
*#Granule cell layer -- "very blue" on H&E.
*#*Granule cells (many), interneurons (Golgi cells --few in number). (???)
*Images:
**[http://www.stonybrookmedicalcenter.org/sbumcfiles/images/227_001.jpg Cerebellar cortex - micrograph (stonybrookmedicalcenter.org)].
**[http://upload.wikimedia.org/wikipedia/commons/7/7c/Gray706.png Cerebellar cortex - schematic (Gray's Anatomy - WC)].


====Cerebral cortex====
DDx:
Layers (superficial to deep):
*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> 
#Molecular layer.
*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>
#*Empty appearing.
 
#Outer granular layer.
=====Images=====
#Outer pyramidal layer.
<gallery>
#Inner granular layer.
Image:Central_chromatolysis_-_intermed_mag_-_cropped.jpg | Central chromatolysis - intermed. mag. (WC)
#*Not prominent in frontal cortex.
Image:Central_chromatolysis_-_nf_-_very_high_mag.jpg | Central chromatolysis - NF stain - very high mag. (WC)
#*Where the thalamic axons end.
</gallery>
#Inner pyramidal layer.
====Axonal swellings====
#*Location of ''Betz neurons'' - large motor neurons of cerebral cortex.
H&E:
#Polymorphic layer.
*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:
Images:
*[http://commons.wikimedia.org/wiki/File:Cajal_cortex_drawings.png Cajal drawings - different areas (WC)].
*[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.ruf.rice.edu/~lngbrain/cglidden/Lab8_fig1.gif Different stains (rice.edu)].
*[http://www.neuropathologyweb.org/chapter3/images3/3-pvlaxonsweling.jpg Axonal swelling (neuropathologyweb.org)].
*[http://williamcalvin.com/bk7/img/bk7p31.jpg (williamcalvin.com)].
 
*[http://www.benbest.com/science/anatmind/anatmd5.html (benbest.com)].
=====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>


==Histopathology==
===Glial changes===
*Reactive astrocytes.
====Astrocyte changes====
**Eosinophilic cytoplasm.
Reactive astrocytes:
**Peripheral nucleus.
*Approximately equally-spaced; distance between neighbouring astrocytes is ~2x (or more) the cell size.
**Well-defined cell border.
*Well-defined cell border.
**Many branching processes.
*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 astrocytes:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 2 July 2010.</ref>
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 nuclei.
*Large cleared nucleus - '''key feature'''.
*Indistinct cytoplasm.
*Indistinct cytoplasm.
*Images:
*Found in the context of ''hepatic encephalopathy'' in basal ganglia and lower layers of cortex.<ref name=Ref_Klatt202>{{Ref Klatt|202}}</ref>
**[http://commons.wikimedia.org/wiki/File:Alzheimer_type_II_astrocyte_high_mag.jpg Alzheimer type II astrocytes (WC)].
*Images:
**[http://neuroquiz.com/?page=image&topic=1&qid=2714 Alzheimer type II astrocytes (neuroquiz.com)].
**[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)] .
**[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)].


*Axonal swellings
====Reactive change vs. malignancy====
**Image: [http://www.neuropathologyweb.org/chapter3/images3/3-pvlaxonsweling.jpg Axonal swelling] - neuropathologyweb.org.
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====
see also:
* [[Viruses]]
* [[Microorganisms]]
 
=====General=====
DDx:
*Viral encephalitis (Neurotrophic viruses):<ref>{{Cite journal  | last1 = Ludlow | first1 = M. | last2 = Kortekaas | first2 = J. | last3 = Herden | first3 = C. | last4 = Hoffmann | first4 = B. | last5 = Tappe | first5 = D. | last6 = Trebst | first6 = C. | last7 = Griffin | first7 = DE. | last8 = Brindle | first8 = HE. | last9 = Solomon | first9 = T. | title = Neurotropic virus infections as the cause of immediate and delayed neuropathology. | journal = Acta Neuropathol | volume = 131 | issue = 2 | pages = 159-84 | month = Feb | year = 2016 | doi = 10.1007/s00401-015-1511-3 | PMID = 26659576 }}</ref>
** Eteroviruses are the most common cause of aseptic meningitis.
***Coxackie Virus.
***Enteric cytopathic human orphan (ECHO) virus.
** Human Herpesviruses (HSV1, HSV2, VZV, CMV, EBV, Roseola)
*** HSV encephalitis has high mortality without acyclovir treatment.
*** Childhood cerebellitis mainly associated with varicella.
*** VZV is the second most common viral meningitis after enterovirus.
** Measles virus(worldwide more than 100.000 deaths annually).
***Is linked to [[acute demyelinating encephalomyelitis]] (ADEM) and Subacute sclerosing encephalitis (SSPE).
** Seasonal influenza A virus (highest patogenic potential: avian influenza H5N1).
** Polio and Non-Polio Enterovirus (mostly children).
***Although massive eradication: Polio still existent in Pakistan, Afghanistan, Nigeria.
** Rabies virus
** Tick-borne encephalitis virus (Europe, Siberia, Russian far-east).
** West-Nile virus (US, Southern europe).
** St. Louis encephalitis virus (US).
** Japanese encephalitis virus (South, south-east asia, high disability rate).
** La Crosse virus (esp. children, midwest & eastern US).
** Borna disease virus (VSBV-1).
** Equine encephalitis viruses (EEEV, VEEV, WEEV, CHIKV).
*Paraneoplastic syndromes.
*Autoimmune antibody-mediated limbic encephalitis (NMDAR).
*Purulent bacterial encephalitis
**Streptococcus, [[Actinomyces]] ....
*Septic metastatic encephalitis
**microabscesses, local astrogliosis, two or more granulocytic infiltrates without relation to vessel.<ref>{{Cite journal  | last1 = Tauber | first1 = SC. | last2 = Bunkowski | first2 = S. | last3 = Brück | first3 = W. | last4 = Nau | first4 = R. | title = Septic metastatic encephalitis: coexistence of brain damage and repair. | journal = Neuropathol Appl Neurobiol | volume = 37 | issue = 7 | pages = 768-76 | month = Dec | year = 2011 | doi = 10.1111/j.1365-2990.2011.01196.x | PMID = 21696418 }}</ref>
*Septic embolic encephalitis
**Embolic endocarditis, Stroke-like lesions.<ref>{{Cite journal  | last1 = Bitsch | first1 = A. | last2 = Nau | first2 = R. | last3 = Hilgers | first3 = RA. | last4 = Verheggen | first4 = R. | last5 = Werner | first5 = G. | last6 = Prange | first6 = HW. | title = Focal neurologic deficits in infective endocarditis and other septic diseases. | journal = Acta Neurol Scand | volume = 94 | issue = 4 | pages = 279-86 | month = Oct | year = 1996 | doi =  | PMID = 8937541 }}</ref>
*Non-purulent bacterial encephalitis
** [[Tuberculosis]]...
 
=====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.
 
<gallery>
File:CNS_lymphocytic_encephalitis_frozen_section.jpg | Intraoperative appearance of a lymphocytic encephalitis (WC/jensflorian)
File:CNS_lymphocytic_encephalitis_FFPE_section.jpg | Perivascular inflammation in a lymphocytic encephalitis (WC/jensflorian)
File:HSV_hemorrhagic_encephalitis.jpg | Hemorrhage in HSV encephalitis (WC/jensflorian)
File:HSV_necrotizing_encephalitis.jpg | HSV encephalitis, higher magnification (WC/jensflorian)
File:Cmv_status_verrucosus.jpg | Neonatal brain with migration disturbances due to CMV infection (WC/jensflorian)
File:Cmv_neuronal_inclusions.jpg | Neuronal nuclear inclusions in a neonatal CMV infection (WC/jensflorian)
File:Rabies encephalitis PHIL 3368 lores.jpg | Rabies encephalitis (CDC.gov)
File:Rabies negri bodies brain.jpg | Negri bodies in Purkinje cells (CDC.gov)
</gallery>
 
====Vasculitis====
DDx Cerebral vasculitis / angiitis:
*[[Systemic lupus erythematosus]] (SLE)
*[[Rheumatoid arthritis]].
*Medications and drugs (amphetamine, cocaine and heroin).
*Paraneoplastic(lymphomas, leukemia and lung cancer).
*[[Granulomatosis_with_polyangiitis]]
*[[Giant cell arteritis]]
*[[Takayasu's arteritis]]
*[[Polyarteritis nodosa]]
*Beta-amyloid-related angiitis (ABRA)
 
<gallery>
File:ABRA_HE_40x.jpg | Beta-amyloid related angitis, HE (WC)
File:ABRA_beta-amyloid_40x.jpg |  Beta-amyloid related angiitis, abeta IHC (WC)
File:Giant cell arteritis -- low mag.jpg | Giant cell arteritis, HE (WC)
</gallery>


===Architecture===
===Architecture===
*Rosette = circular/flower-like arrangement of cells<ref name=pmid16551982>PMID 16551982</ref>
====Rosettes====
*Pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre<ref name=pmid16551982>PMID 16551982</ref>
*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>
*Rosenthal fibres = worm-like or corkscrew-like eosinophilic bodies.
 
**Image: [http://en.wikipedia.org/wiki/File:Rosenthal_HE_40x.jpg Rosenthal fibres] - wikipedia.org.
*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>
*Pseudopallisading
**[[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) .
**Neuroblastoma
 
*Flexner-Wintersteiner rosette = rosette with empty centre (donut hole).<ref name=pmid16551982/>
**[[Retinoblastoma]]s.
**[[Pineoblastomas]].
**[[Medulloepithelioma]]s.
 
*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]].
**[[RGNT]] - Rosette forming glioneuronal tumor of the IVth ventricle.
 
*Radial (cartwheel) profiles = neoplastic cells anchoring to stromal vessels, shorter processes than in ependymal pseudorosettes
**[[Astroblastoma]].
**[[Glioblastoma]].
 
*Multilayered rosettes
**[[Ependymomblastoma]]s.
**[[Medulloepithelioma]]s.
 
*Meningeothelial rosettes
**[[Meningioma]] - a rare pattern.<ref>{{Cite journal  | last1 = Liverman | first1 = C. | last2 = Mafra | first2 = M. | last3 = Chuang | first3 = SS. | last4 = Shivane | first4 = A. | last5 = Chakrabarty | first5 = A. | last6 = Highley | first6 = R. | last7 = Hilton | first7 = DA. | last8 = Byrne | first8 = NP. | last9 = Wesseling | first9 = P. | title = A clinicopathologic study of 11 rosette-forming meningiomas: a rare and potentially confusing pattern. | journal = Acta Neuropathol | volume = 130 | issue = 2 | pages = 311-3 | month = Aug | year = 2015 | doi = 10.1007/s00401-015-1456-6 | PMID = 26106026 }}</ref>
 
<gallery>
Image:Neuroblastoma Homer Wright rosettes HE.jpg | Homer-Wright rosettes (WC).
Image:RGNT HE 2.jpg | Neurocytic rosettes (WC).
Image:Ependymoma H&E.jpg | Perivascular pseudorosette (WC).
Image:Ependymoblastoma ETMRjpg.jpg | Multilayered rosettes (WC).
Image:Ependymoblastomatous Rosette.jpg | Ependymoblastous rosettes (WC/Marvin101).
Image:Ependymoma true ependymal rosettes and pseudorosettes.jpg | True ependymal rosettes and pseudorosettes (WC).
Image:Astroblastoma HE Specimen.jpg | Radial (cartwheel) profiles (WC).
</gallery>


Notes: Good set of articles - <ref>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=Neuropathology%20for%20the%20neuroradiologist</ref>
====Other important histological features====
*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 [[astrocyte]]s.<ref>{{Ref MBNP|11}}</ref>
<gallery>
File:Pilocytic Micro.jpg | Eosinophilic granular bodies in pilocytic astrocytoma smear (WC/AFIP)
File:PXA HE x20.jpg | Eosinophilic granular body in a pleomorphic xanthoastrocytoma (WC/jensflorian)
</gallery>
 
*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]].
<gallery>
File:GBM pseudopalisading necrosis.jpg | Pseudopalisading necrosis in a glioblastoma (WC/jensflorian)
</gallery>
 
*Perivascular lymphocytic cuffing - Lymphocytes surrounding vessels.
** Seen in many inflammatory conditions including MS.
** Often seen in [[ganglioglioma]] and [[pleomorphic xanthoastrocytoma]].
** Less common in some gemistocytic [[astrocytoma]].
*** No association with survival. <ref>{{Cite journal  | last1 = Rossi | first1 = ML. | last2 = Jones | first2 = NR. | last3 = Candy | first3 = E. | last4 = Nicoll | first4 = JA. | last5 = Compton | first5 = JS. | last6 = Hughes | first6 = JT. | last7 = Esiri | first7 = MM. | last8 = Moss | first8 = TH. | last9 = Cruz-Sanchez | first9 = FF. | title = The mononuclear cell infiltrate compared with survival in high-grade astrocytomas. | journal = Acta Neuropathol | volume = 78 | issue = 2 | pages = 189-93 | month =  | year = 1989 | doi =  | PMID = 2750489 }}</ref>
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in [[ganglioglioma]] (WC/jensflorian)
</gallery>
 
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===
===Inclusion bodies===
*Negri bodies.
*Negri bodies.
**Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
**Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
**Rabies.
**[[Rabies]].
**Image: [http://commons.wikimedia.org/wiki/File:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg Negri bodies (WC/CDC)].
<gallery>
Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg | Negri bodies. (WC/CDC)
</gallery>
*Owl eye inclusions.
**Basiopilic neuronal inclusions in enlarged cells, typically seen in CMV encephalitis
<gallery>
Image:CMV encephalitis owl eye inclusions HE stain.jpg | Owl eye inclusions
</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<br>[[AKA]] granular bodies
| granular and eosinophilic ~50 micrometers
| neurodegenerative disease, neuroaxonal dystrophies, aging
| ?Comment
| ?Image
|-
| Cowdry type 1<br>AKA Cowdry type A
| eosinophilic & round + halo
| [[herpes simplex virus]]
| can be confused with <br>Lewy body, Marinesco body
| ?Image
|-
| Lewy body
| round cytoplasmic eosinophilic<br> body +/- pale halo
| [[Parkinson disease]], dementia with Lewy bodies
| morphology dependent on <br>location in brain; +ve for alpha-synuclein, <br>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<br>~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]], <br>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 <br>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]
|-
<!-- | Feature
| ?Appearance
| ?Associated disease
| ?Comment
| ?Image
|- -->
|}
 
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.
*MAP2C. <ref>{{Cite journal  | last1 = Blümcke | first1 = I. | last2 = Müller | first2 = S. | last3 = Buslei | first3 = R. | last4 = Riederer | first4 = BM. | last5 = Wiestler | first5 = OD. | title = Microtubule-associated protein-2 immunoreactivity: a useful tool in the differential diagnosis of low-grade neuroepithelial tumors. | journal = Acta Neuropathol | volume = 108 | issue = 2 | pages = 89-96 | month = Aug | year = 2004 | doi = 10.1007/s00401-004-0873-8 | PMID = 15146346 }}</ref>
*Ki-67 (MIB-1).
Useful additional markers:
*IDH1(R132H) in Astrocytic/Oligodendroglial tumors. <ref>{{Cite journal  | last1 = Paulus | first1 = W. | title = GFAP, Ki67 and IDH1: perhaps the golden triad of glioma immunohistochemistry. | journal = Acta Neuropathol | volume = 118 | issue = 5 | pages = 603-4 | month = Nov | year = 2009 | doi = 10.1007/s00401-009-0600-6 | PMID = 19847448 }}</ref>
*ATRX in mixed gliomas. <ref>{{Cite journal  | last1 = Reuss | first1 = DE. | last2 = Sahm | first2 = F. | last3 = Schrimpf | first3 = D. | last4 = Wiestler | first4 = B. | last5 = Capper | first5 = D. | last6 = Koelsche | first6 = C. | last7 = Schweizer | first7 = L. | last8 = Korshunov | first8 = A. | last9 = Jones | first9 = DT. | title = ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. | journal = Acta Neuropathol | volume = 129 | issue = 1 | pages = 133-46 | month = Jan | year = 2015 | doi = 10.1007/s00401-014-1370-3 | PMID = 25427834 }}</ref>
*EMA in Ependymal tumors. <ref>{{Cite journal  | last1 = Hasselblatt | first1 = M. | last2 = Paulus | first2 = W. | title = Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. | journal = Acta Neuropathol | volume = 106 | issue = 4 | pages = 385-8 | month = Oct | year = 2003 | doi = 10.1007/s00401-003-0752-8 | PMID = 12898159 }}</ref>
*OLIG-2 usually -ve in Ependymomas. <ref>{{Cite journal  | last1 = Ishizawa | first1 = K. | last2 = Komori | first2 = T. | last3 = Shimada | first3 = S. | last4 = Hirose | first4 = T. | title = Olig2 and CD99 are useful negative markers for the diagnosis of brain tumors. | journal = Clin Neuropathol | volume = 27 | issue = 3 | pages = 118-28 | month =  | year =  | doi =  | PMID = 18552083 }}</ref><ref>{{Cite journal  | last1 = Otero | first1 = JJ. | last2 = Rowitch | first2 = D. | last3 = Vandenberg | first3 = S. | title = OLIG2 is differentially expressed in pediatric astrocytic and in ependymal neoplasms. | journal = J Neurooncol | volume = 104 | issue = 2 | pages = 423-38 | month = Sep | year = 2011 | doi = 10.1007/s11060-010-0509-x | PMID = 21193945 }}</ref>
===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 tumours originating in the brain (in adults) are [[glioma]]s. More than 50% of these are classified as [[glioblastoma]] which has a horrible prognosis.
 
=Non-tumour=
==Vascular disorders==
===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.
 
===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).
 
===Cerebral amyloid angiopathy associated with inflammation (I-CAA)===
* Cognitive decline.
* Microbleedings in MRI.
* Responsive to steroids.
* Abeta deposits in vessels.
* Perivascular lymphocytic infiltrate (but no vasculitis!).
* Giant cells may be present.
 
===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>
*[[Vascular_malformations#Arteriovenous_malformation|Arteriovenous malformation]].
*Varix.
*Venous angioma.
*[[Vascular_malformations#Cavernous_hemangioma|Cavernous hemangioma]]  (Cavernoma).
*Capillary teleangiectasia.
Also see: ''[[Sturge-Weber syndrome]]''.
 
===Atherosclerosis===
{{Main|Vascular_disease#Atherosclerosis}}
*Intracranial atherosclerosis most common at circle of Willis.
*Macroscopic yellow discoloration.
*Luminal stenosis and eccentric intimal thickening.
<gallery>
File:Carotid Plaque (121061911).jpg|Plaque of the carotid bifurcation (Ed Uthman).
</gallery>
 
===Other large arterial diseases===
*[[Vascular_disease#Fibromuscular_dysplasia|Fibromuscular dysplasia]].
*Moyamoya disease.
**Progressive stenosis of basal intracranial arteries and abnormal vascularization.
*[[Aortic dissection|Arterial dissection]].
*[[Giant cell arteritis]].
*[[Takayasu's arteritis]].
*[[Antiphospholipid antibody syndrome|Antiphospholipid antibody]] mediated thrombosis.
 
===Microangiopathy===
*Defined as Small vessel disease (<300µm in transverse section).
*Includes atherosclerosis and cerebral amyloid angiopathy.
Other causes:
*Primary angitis of the CNS (PACNS).
*[[Polyarteritis nodosa]].
*[[Granulomatosis with polyangiitis]] (Wegener's granulomatosis).
*[[Lymphomatoid granulomatosis]].
*Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (commonly abbreviated ''CADASIL'').
{{Main|Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy}}


==Ring enhancing lesions==
===Hypoxic-ischemic encephalopathy===
In [[HIV]]/AIDS patients... mass on CT if infection:
*Abbreviated ''HIE''.
*Toxoplasmosis - most common.<ref>MUN. Feb 3, 2009.</ref>
{{Main|Hypoxic-ischemic encephalopathy}}
**Hypoxia: reduction in oxygen supply or utilization.
**Ischemia: reduction in blood supply.
 
===Cerebrovascular accident===
*Abbreviated ''CVA''.
*[[AKA]] ''stroke''.
{{Main|Cerebrovascular accident}}
*Stroke includes:
**Infarction (ischemia in defined vascular distribution persisting for at least 24hrs).
**Intracrebral hemorrhage (focal blood accumulation in the brain parenchyma).
**Subarachnoid hemorrhage (SAH).
**Cerebral venous thrombosis (CVT).  


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


==Alcohol & CNS==
==Alcohol & CNS==
Pathology:<ref>http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract</ref>
===Clinical===
*Morel's laminar sclerosis
*central pontine myelinolysis
*Wernicke's encephalopathy  
*Wernicke's encephalopathy  
**Mnemonic ''WACO'':
**Mnemonic ''WACO'':
Line 250: Line 664:
***Ocular Sx (CN IV palsy).
***Ocular Sx (CN IV palsy).
**Cause: thiamine deficiency.
**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>
*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.


==Non-tumour==
==Meningitis==
==Acute disseminated encephalomyelitis==
===General===
===General===
*Thought to be autoimmune; often associated with/preceded by by viral illness.<ref name=pmid17438235>{{cite journal |author=Tenembaum S, Chitnis T, Ness J, Hahn JS |title=Acute disseminated encephalomyelitis |journal=Neurology |volume=68 |issue=16 Suppl 2 |pages=S23–36 |year=2007 |month=April |pmid=17438235 |doi=10.1212/01.wnl.0000259404.51352.7f |url=}}</ref>
*Definition: inflammation of the meninges (pia mater, arachnoid membranes, dura mater).
*May mimic multiple sclerosis.
 
*Abbreviated "ADEM".
Classic clinical presentation:
*Neck stiffness.
*Fever.
*+/-Headache.
*+/-Decreased level of consciousness.
 
CSF findings:
{| class="wikitable sortable"
! Type
! Glucose
! Protein
! Cells
! Cytopathology
|-
| Bacterial, acute
| low
| high
| neutrophils
| [[File:Purulent_CSF.jpg|100px|center|]][[CSF_cytopathology#Acute_bacterial_meningitis|Cytophathology]]
|-
| Viral
| normal
| slight elevation
| lymphocytes
| [[CSF_cytopathology#Viral_meningitis|Cytophathology]]
|}
 


===Diagnosis===
 
*Need to r/o infection (with lumbar puncture).
====Etiology====
*No old plaques on imaging (MRI).
*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 | Streptococcus Meningitis. (WC/Dr. Edwin P. Ewing, Jr.)
File:Haemophilus influenzae meningitis 5003 lores.jpg | Hemophilus influenza Meningitis. (WC/CDC)
File:Pneumococcal meningitis.jpg | Pneumococcus Meningitis. (WC/Dr. Yale Rosen)
File:Meningitis-MRI.JPG | Bacterial Meningitis MRI (WC/MBq)
</gallery>


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


===Tx===
Main DDx:
*Steroids.
*[[Lymphoma]].
*Plasmapheresis.


===DDx===
====Image====
*Multiple sclerosis.
<gallery>
Image:Meningitis_Histopathology.jpg | Bacterial meningitis. (WC/Marvin101)
</gallery>


==Cysts==
==Cerebral abscess==
===General===
===General===
*All are "benign", but some may be fatal due to spatial constraints.
*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.
 
==Malformation of cortical development(MCD) ==
===Lissencephaly===
* Greek: ‘lissos': smooth and ‘enkephalos': brain.
* Absent (agyria) or decreased (pachygyria) convolutions.
* Cortical thickening
* Smooth cerebral surface
* Subtypes with different layering: 2-layered, 3-layered, and 4-layered forms.
* Heterotopic neurons in a pattern suggestive of laminar organization.
* 14 LIS mutations account for 90% of all cases.<ref name="pmid27781032">{{cite journal |authors=Parrini E, Conti V, Dobyns WB, Guerrini R |title=Genetic Basis of Brain Malformations |journal=Mol Syndromol |volume=7 |issue=4 |pages=220–233 |date=September 2016 |pmid=27781032 |pmc=5073505 |doi=10.1159/000448639 |url=}}</ref>
 
===Polymicrogyria===
* Abnormal cortical lamination.
* Abnormally small and partly fused gyri.
* Can be unilateral, bilateral and symmetrical.
* Intellectual disability.
* Sometimes severe encephalopathy.
* Pharmacoresistant epilepsy
* Cortical lamination can be unlayered or four-layered.
** Unlayered:  Unorganized radial distribution of neurons.
** Four-layered:  Molecular layer, outer neuronal layer, nerve fiber layer, and inner neuronal layer.
* 1q trisomy in unilateral cases.<ref name="pmid32979071">{{cite journal |authors=Kobow K, Jabari S, Pieper T, Kudernatsch M, Polster T, Woermann FG, Kalbhenn T, Hamer H, Rössler K, Mühlebner A, Spliet WGM, Feucht M, Hou Y, Stichel D, Korshunov A, Sahm F, Coras R, Blümcke I, von Deimling A |title=Mosaic trisomy of chromosome 1q in human brain tissue associates with unilateral polymicrogyria, very early-onset focal epilepsy, and severe developmental delay |journal=Acta Neuropathol |volume=140 |issue=6 |pages=881–891 |date=December 2020 |pmid=32979071 |doi=10.1007/s00401-020-02228-5 |url=}}</ref>
 
==Epilepsy==
{{Main|Epilepsy}}
===Focal cortical dysplasia (FCD)===
*Localized malformations of the cortex.
*Frequently associated with epilepsy in children.
*Includes cortical dyslamination, cytoarchitectural changes and white matter abnormalities.
*Current consensus: ILAE classification scheme 2011 <ref>{{Cite journal  | last1 = Blümcke | first1 = I. | last2 = Aronica | first2 = E. | last3 = Miyata | first3 = H. | last4 = Sarnat | first4 = HB. | last5 = Thom | first5 = M. | last6 = Roessler | first6 = K. | last7 = Rydenhag | first7 = B. | last8 = Jehi | first8 = L. | last9 = Krsek | first9 = P. | title = International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: A consensus Task Force report from the ILAE Commission on Diagnostic Methods. | journal = Epilepsia | volume = 57 | issue = 3 | pages = 348-58 | month = Mar | year = 2016 | doi = 10.1111/epi.13319 | PMID = 26839983 }}
</ref>(based on previous classification by Palmini 2004):
 


===List of cysts===
*Type I FCD (focal)
*Colloid cyst.<ref>MUN. 11 Mar 2009.</ref>
**Ia: Abnormal radial cortical lamination.
**Columnar epithelium.
**Ib: Abnormal tangential cortical lamination.
*Arachnoid cyst - considered precursor of meningioma.
**Ic: Abnormal radial and tangential cortical lamination.
**Psammoma bodies.
**Clumps of cells.
**Whorled pattern.
*Dermoid cyst.
**Skin + adnexal structures.
**... think of ovarian dermoid.
*Epidermoid.
*Choriod cyst.
**?


*Neuroenteric cyst.
*Epithelial cyst.


==Dementia==
*Type II FCD (focal)
*Alzheimer's dementia.
**IIa: Presence of dysmorphic neurons.
*Vascular.
**IIb: Presence of dysmorphic neurons and balloon cells.
**multi-infarct dementia.
*Parkinson's associated dementia.
*Lewy body dementia.
*Alcohol-related dementia.
*Fronto-temporal dementia (Pick disease).
*Multisystem atrophy.


Mnemonic ''VITAMIN D VEST'':<ref>TN06 PS19</ref>
*Vitamin deficiency (B12, folate, thiamine).
*Infection (HIV).
*Trauma.
*Anoxia.
*Metabolic (Diabetes).
*Intracranial tumour.
*Normal pressure hydrocephalus.
*Degenerative (Alzheimer's, Huntington's, CJD).
*Vascular.
*Endocrine.
*Space occupying lesion (chronic subdural hematoma).
*Toxins (alcohol).


===Lewy body dementia===
*Type III FCD (associated with other lesion)
*Parkinsonian features.
**IIIa: FCD associated with [[Epilepsy#Hippocampal_sclerosis|hippocampal sclerosis]].
*Hallucinations (visual).
**IIIb: FCD adjacent to a brain tumor.
*Progressive cog. decline with fluctuations.
**IIIc: FCD adjacent to vascular malformation.
**IIIc: FCD associated with previous injury (trauma, inflammation...).


===Multiple system atrophy===
*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>
**Alpha-synuclein is implicated in a number of neurodegenerative diseases.<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>


==Brain tumours==
<gallery>
{{main|Neuropathology tumours}}
File:FCDIIa dysmorphic neurons HE.jpg|Dysmorphic neurons in FCD (HE)
Tumours are a big part of neuropathology.
File:FCDIIa neuronal heterotopia neun.jpg|Heterotopic neurons (NeuN)
</gallery>


==Paediatric pathology==
===Hamartia===
===Joubert syndrome===
* Small collection of ectopic glioneuronal cells.
*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>
**Morpholology resembling oligodendroglial-like cells. <ref>{{Cite journal  | last1 = Kasper | first1 = BS. | last2 = Stefan | first2 = H. | last3 = Buchfelder | first3 = M. | last4 = Paulus | first4 = W. | title = Temporal lobe microdysgenesis in epilepsy versus control brains. | journal = J Neuropathol Exp Neurol | volume = 58 | issue = 1 | pages = 22-8 | month = Jan | year = 1999 | doi =  | PMID = 10068310 }}</ref>
* Mostly amygdala, less common in hippocampus or temporal lobe.
* Can coexist with focal cortical dysplasia.


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


==Stroke==
===Multiple sclerosis===
===Gross===
*Abbreviated ''MS''.
*Soft/mushy brain.
{{Main|Multiple sclerosis}}
*Older infarcts.
**A "roof" is present - a thin submeningeal layer is preserved by the CSF.<ref>MUN. 16 December 2009.</ref>
***"Roof" is absent in trauma.
**Cavity - in older infarcts.
***''Multiple sclerosis'' does not cavitate.


==Hypoxic-ischemic encephalopathy==
===Osmotic demyelination syndrome===
===General===
{{Main|Osmotic demyelination syndrome}}
*Often due to ''cardiac arrest'', i.e. global ischemia.
*Previously known as ''central pontine myelinolysis'' (abbreviated ''CPM'').
*Triple watershed area = parieto-occipital cortex, extrastriate occipital cortex.


===Microscopic===
===Acute disseminated encephalomyelitis===
Features:
*Abbreviated ''ADEM''.
*Hippocampal ischemic changes:
{{Main|Acute disseminated encephalomyelitis}}
**Loss of neurons in CA1, CA3 and CA4 +/- "cavitation".
***Neuronal loss: No blue (nuclei) where there should be some.
***Cavitation: bubbles/clear spaces where there should be none.
**CA2 neurons preserved.


*"Anoxic neurons".<ref>URL: [http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html]. Accessed on: 12 July 2010.</ref>
===Neuromyelitis optica===
**Shrunken neurons with intensely eosinophilic cytoplasm and pyknotic (shrunken) nuclei.
*Abbreviated ''NMO''.
**Images:
***[http://www.neuropathologyweb.org/chapter2/images2/2-1HIE.jpg Anoxic neurons (neuropathologyweb.org)].
***[http://commons.wikimedia.org/wiki/File:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg Anoxic neurons (???) (WC)].


==Multiple sclerosis==
General:
===General===
*Rare autoimmune disease - once considered a variant of [[multiple sclerosis]].
*A bread 'n butter disease of neurology in Canada.
**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>


===Radiologic/Gross===
Diagnosis:
Features:<ref>URL: [http://library.med.utah.edu/kw/ms/path.html http://library.med.utah.edu/kw/ms/path.html]. Accessed on: 12 July 2010.</ref>
*NMO-IgG.
*White matter lesions.
**Cerebrum (classically): periventricular distribution.
**Optic nerves (optic neuritis) - classic presentation.


===Microscopic===
Clinical - preferentially:
Features:<ref>URL: [http://library.med.utah.edu/kw/ms/path.html http://library.med.utah.edu/kw/ms/path.html]. Accessed on: 12 July 2010.</ref>
*Eye (optic neuritis).
*Perivascular inflammation.
*Spinal cord (myelitis).
*Demyelination.
**Subcortical myelinated fibers are often spared.


Classification of MS lesions:
Microscopic:
*Early active.
*Inflammation - lymphocytes, macrophages.
*Inactive.
*Reactive astrocytes.
*Early remyelinating.
*Late remyelinating.


==Weird stuff==
Images:
==Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)==
*[http://path.upmc.edu/cases/case637.html Neuromyelitis optica - several images (upmc.edu)].
===General===
*Autosomal dominant disorder - the name implies.<ref name=pmid19174371>{{Cite journal  | last1 = Tikka | first1 = S. | last2 = Mykkänen | first2 = K. | last3 = Ruchoux | first3 = MM. | last4 = Bergholm | first4 = R. | last5 = Junna | first5 = M. | last6 = Pöyhönen | first6 = M. | last7 = Yki-Järvinen | first7 = H. | last8 = Joutel | first8 = A. | last9 = Viitanen | first9 = M. | title = Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients. | journal = Brain | volume = 132 | issue = Pt 4 | pages = 933-9 | month = Apr | year = 2009 | doi = 10.1093/brain/awn364 | PMID = 19174371 }}
</ref>
*Cases strokes in 40-50 year-old.
*Characteristic MRI findings - present in asymptomatic individuals with mutation.


===Etiology===
IHC:
*Mutation of ''Notch 3'' gene.<ref name=pmid15537516>{{Cite journal  | last1 = Kalaria | first1 = RN. | last2 = Viitanen | first2 = M. | last3 = Kalimo | first3 = H. | last4 = Dichgans | first4 = M. | last5 = Tabira | first5 = T. | title = The pathogenesis of CADASIL: an update. | journal = J Neurol Sci | volume = 226 | issue = 1-2 | pages = 35-9 | month = Nov | year = 2004 | doi = 10.1016/j.jns.2004.09.008 | PMID = 15537516 }}</ref>
*Mixed lymphocyte population with CD3 > CD20.
*Aquaporin-4 loss.


===Diagnosis===
===Progressive multifocal leukoencephalopathy===
*Proven ''Notch 3'' mutation.
*Abbreviated ''PML''.
*Can be diagnosed on a skin biopsy.
{{Main|Progressive multifocal leukoencephalopathy}}
*IHC for ''Notch 3'' -- +ve staining in Notch 3 mutants.


===Histology===
Features:
*Subcortical infarcts.
**Patches of (non-myelinated) tissue within the white matter deep to the cortex with abundant macrophages.


Note:
*No cortical involvement -- this is unlike ''multiple sclerosis''.


DDx:
=Cysts=
*Amyloidosis.
===General===
*Binswanger's disease - multi-infarct dementia affecting subcortical white matter.
*All are "benign", but some may be fatal due to spatial constraints.
**Often diagnosed as ''Alzheimer's disease'' in the past.


===Electron microscopy===
===List of cysts===
*Granular osmiophilic material (GOM).
*[[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.
*Cyst with a mural nodule tumor of the brain.
**Commonly seen in: <ref>{{Cite journal  | last1 = Raz | first1 = E. | last2 = Zagzag | first2 = D. | last3 = Saba | first3 = L. | last4 = Mannelli | first4 = L. | last5 = Di Paolo | first5 = PL. | last6 = D'Ambrosio | first6 = F. | last7 = Knopp | first7 = E. | title = Cyst with a mural nodule tumor of the brain. | journal = Cancer Imaging | volume = 12 | issue =  | pages = 237-44 | month = Aug | year = 2012 | doi = 10.1102/1470-7330.2012.0028 | PMID = 22935908 }}</ref>
**[[Hemangioblastoma]]
**[[Craniopharyngioma]]
**[[Ganglioglioma]]
*Others.


==Binswanger's disease==
==Colloid cyst==
===General===
===General===
*Multi-infarct dementia affecting subcortical white matter.
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>
*Waste-basket diagnosis; diagnosed if CADASIL and amyloidosis have been excluded.
*Headache - may be relieved by lying down.
*Diagnosis has been controversial -- most with this entity (in the past) were diagnosed with ''Alzheimer's disease''.
*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===
===Microscopic===
Features:
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>
*Subcortical lesions that replace the myelin consisting of macrophages.
*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/>


==Prion diseases==
=Paediatric pathology=
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>
==Kernicterus==
*Misfolded cell-surface protein called PrP(C).
===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>


Includes:<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>
===Gross===
*Creutzfeldt-Jakob disease (CJD).
*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>
*Sporadic fatal insomnia (sFI).
**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.


==Creutzfeldt-Jakob disease==
Note:
*Commonly abbreviated as ''CJD''.
*May not be specific.<ref name=pmid7063283/>
*Rare.
*Incurable disease.


*Variant Creutzfeldt-Jakob disease (vCJD).
Image:
**Associated with bovine spongiform encephalopathy.
*[http://www.flickr.com/photos/neonatal-box/6275988844/ Kernicterus (flickr.com)].
**Should sample: spleen, lymph nodes, tonsils.<ref name=Ref_HospAuto83>{{Ref HospAuto|83}}</ref>


===Microscopic===
===Microscopic===
Features:
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>


Images:
===Epidemiology===
*[http://commons.wikimedia.org/wiki/File:SpongiformChangeCJD.jpg CJD (WC)].
*Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.<ref name=ninds_joubert/>
*[http://commons.wikimedia.org/wiki/File:VCJD_Tonsil.jpg vCJD - IHC (WC)].


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


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


==External links==
=External links=
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[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://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://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]]
[[Category:Neuropathology]]
Michael
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