Neuropathology

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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.

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

Neuroanatomy

Main article: Neuroanatomy

This is a large topic. It covered in a separate article, that also covers grossing.

Grossing

This is covered in the neuroanatomy article.

Normal histology

Main article: Neurohistology

This is a big topic. It is covered in a separate article called neurohistology.

Histopathology

Astrocyte changes

Reactive astrocytes.

  • Eosinophilic cytoplasm.
  • Peripheral nucleus.
  • Well-defined cell border.
  • Many branching processes.

Types

Alzheimer type II astrocyte:[1]

Bergmann gliosis (in the cerebellum):[2]

Creutzfeldt cell:[2]

  • Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
  • Finding associated with demyelinating disease.

Other

Axonal swellings:

Architecture

  • Rosette = circular/flower-like arrangement of cells[3]
  • Pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre[3]
  • Rosenthal fibres = worm-like or corkscrew-like eosinophilic bodies.
  • Pseudopallisading

Notes: Good set of articles - [4]

Inclusion bodies

  • Negri bodies.
    • Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
    • Rabies.
    • Image: Negri bodies (WC/CDC).
  • Lewy bodies.
    • Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.[5]
    • Image: Lewy body (WC).

Table

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 cytoplasmic thingy Lewy body dementia ?Comment [1]
Lafora body concentric calcification ?Associated disease look like corpora amylacea ?Image
Lipofuscin yellow & granular aging olive, dendate ?Image
Negri body small eosinophic bodies rabies found in hippocampal neurons and Purkinje cells [2]
Hirano body ?Appearance ALS, Parkinson's disease actin crystals, may look like capillaries ?Image
Neurofibrillary tangles flame-shaped cytoplasmic thingy
~30 micrometers 		aging, Alzheimer's disease seen with silver stain ?Image
Pick bodies ?Appearance ?Associated disease ?Comment ?Image
Bunina body size of Nissl granules ?Associated disease ?Comment ?Image

Ring enhancing lesions

In HIV/AIDS patients... mass on CT if infection:

  • Toxoplasmosis - most common.[6]

Ring enhancing lesion (DDx) - mnemonic MAGICAL DR:[7]

  • Metstasis.
  • Abscess.
  • Glioblastoma.
  • Infarct.
  • Contusion.
  • AIDS-related.
  • Lymphoma + HIV assoc. disease (toxoplasma).
  • Demyelination (e.g. multiple sclerosis).
  • Resolving hematoma.

Alcohol & CNS

Clinical

  • Wernicke's encephalopathy
    • Mnemonic WACO:
      • Wernicke's.
      • Ataxia.
      • Confusion, confabulation -- Korsakoff.
      • Ocular Sx (CN IV palsy).
    • Cause: thiamine deficiency.

Pathology

Features:[8]

  • Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex[9] usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.[10]
  • Central pontine myelinolysis.
  • Mammillary body shrinkage.[11]
  • Anterior cerebellar vermis atrophy; weak finding - as also age-related.[12]
    • Vermis atrophy is also seen in schizophrenia.[13]
  • Marchiafava-Bignami Disease:
    • Rare.
    • Demyelination of the corpus callosum.[10]

Common non-specific findings

Non-tumour

Acute disseminated encephalomyelitis

General

  • Thought to be autoimmune; often associated with/preceded by by viral illness.[14]
  • May mimic multiple sclerosis.
  • Abbreviated "ADEM".

Diagnosis

  • Need to r/o infection (with lumbar puncture).
  • No old plaques on imaging (MRI).

Microscopic

Features:

  • Spares subcortical fibres (???)

Tx

  • Steroids.
  • Plasmapheresis.

DDx

  • Multiple sclerosis.

Cysts

General

  • All are "benign", but some may be fatal due to spatial constraints.

List of cysts

  • Colloid cyst.[15]
    • 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.
  • Choriod cyst.
    • ?
  • Neuroenteric cyst.
  • Epithelial cyst.

Dementia

  • Alzheimer's dementia.
  • Vascular.
    • multi-infarct dementia.
  • Parkinson's associated dementia.
  • Lewy body dementia.
  • Alcohol-related dementia.
  • Fronto-temporal dementia (Pick disease).
  • Multisystem atrophy.

Mnemonic VITAMIN D VEST:[16]

  • 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

  • Parkinsonian features.
  • Hallucinations (visual).
  • Progressive cog. decline with fluctuations.

Multiple system atrophy

  • Alpha-synuclein-rich glial cytoplasmic inclusions - finding at autopsy.[17]
    • Alpha-synuclein is implicated in a number of neurodegenerative diseases.[18]

Huntington disease

General

  • Autosomal dominant inheritance.
  • Mutation: unstable CAG repeat.[19]

Gross

  • Missing caudate.[20]

Image: Huntington's disease (ouhsc.edu).

Brain tumours

Main article: Neuropathology tumours

Tumours are a big part of neuropathology. The most common brain tumour is a metastasis. The most common primary tumour is glioblastoma which has a horrible prognosis.

Paediatric pathology

Joubert syndrome

  • Malformation of the cerebellar vermis.[21]

Epidemiology

  • Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.[21]

Stroke

Gross

  • Soft/mushy brain.
  • Older infarcts.
    • A "roof" is present - a thin submeningeal layer is preserved by the CSF.[22]
      • "Roof" is absent in trauma.
    • Cavity - in older infarcts.
      • Multiple sclerosis does not cavitate.
  • Laminar necrosis = (thin) chalky line replace grey mater.[23]

Hypoxic-ischemic encephalopathy

General

  • Often due to cardiac arrest, i.e. global ischemia.
  • Triple watershed area = parieto-occipital cortex, extrastriate occipital cortex.

Microscopic

Features:

  • Hippocampal ischemic changes:
    • 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.

Multiple sclerosis

General

  • A bread 'n butter disease of neurology in Canada.

Radiologic/Gross

Features:[26]

  • White matter lesions.
    • Cerebrum (classically): periventricular distribution.
    • Optic nerves (optic neuritis) - classic presentation.

Microscopic

Features:[27]

  • Perivascular inflammation.
  • Demyelination.
    • Subcortical myelinated fibers are often spared.

Classification of MS lesions:

  • Early active.
  • Inactive.
  • Early remyelinating.
  • Late remyelinating.

Weird stuff

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

General

  • Autosomal dominant disorder - the name implies.[28]
  • Cases strokes in 40-50 year-old.
  • Characteristic MRI findings - present in asymptomatic individuals with mutation.

Etiology

  • Mutation of Notch 3 gene.[29]

Diagnosis

  • Proven Notch 3 mutation.
  • Can be diagnosed on a skin biopsy.
  • 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:

  • Amyloidosis.
  • Binswanger's disease - multi-infarct dementia affecting subcortical white matter.
    • Often diagnosed as Alzheimer's disease in the past.

Electron microscopy

  • Granular osmiophilic material (GOM).

Binswanger's 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.

Prion diseases

Etiology:[30]

  • Misfolded cell-surface protein called PrP(C).

Includes:[30]

  • Creutzfeldt-Jakob disease (CJD).
  • Sporadic fatal insomnia (sFI).

Creutzfeldt-Jakob disease

  • Commonly abbreviated as CJD.
  • Rare.
  • Incurable disease.
  • Variant Creutzfeldt-Jakob disease (vCJD).
    • Associated with bovine spongiform encephalopathy.
    • Should sample: spleen, lymph nodes, tonsils.[31]

Microscopic

Features:

  • Spongy appearance (cytoplasmic vacuolization[32]).

Images:

Immunohistochemistry

Main article: Immunohistochemistry

General

  • S-100.
    • Sensitive... but non-specific, e.g. also stains melanoma.

Glial

  • GFAP (glial fibrillary acidic protein) - should stain perikaryon.

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.[33]

Others

  • APP (amyloid precursor protein) - detects axonal swellings.
  • NF (neurofilament) - detects axonal swellings.

See also

References

  1. ↑ URL: http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html. Accessed on: 2 July 2010.
  2. ↑ 2.0 2.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 18. ISBN 978-0443069826.
  3. ↑ 3.0 3.1 PMID 16551982
  4. ↑ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=Neuropathology%20for%20the%20neuroradiologist
  5. ↑ Marui W, Iseki E, Kato M, Akatsu H, Kosaka K (August 2004). "Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease". Acta Neuropathol. 108 (2): 121–8. doi:10.1007/s00401-004-0869-4. PMID 15235805.
  6. ↑ MUN. Feb 3, 2009.
  7. ↑ TN2005 NS7.
  8. ↑ http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract
  9. ↑ URL: http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939. Accessed on: 22 September 2010.
  10. ↑ 10.0 10.1 Johkura K, Naito M, Naka T (March 2005). "Cortical involvement in Marchiafava-Bignami disease". AJNR Am J Neuroradiol 26 (3): 670–3. PMID 15760886. http://www.ajnr.org/cgi/content/full/26/3/670.
  11. ↑ Shear PK, Sullivan EV, Lane B, Pfefferbaum A (November 1996). "Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia". Alcohol. Clin. Exp. Res. 20 (8): 1489-95. PMID 8947329. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=1996&volume=20&issue=8&spage=1489.
  12. ↑ Torvik A (1987). "Brain lesions in alcoholics: neuropathological observations". Acta Med. Scand. Suppl. 717: 47–54. PMID 3478969.
  13. ↑ Sandyk R, Kay SR, Merriam AE (April 1991). "Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia". Int. J. Neurosci. 57 (3-4): 205–12. PMID 1938163.
  14. ↑ Tenembaum S, Chitnis T, Ness J, Hahn JS (April 2007). "Acute disseminated encephalomyelitis". Neurology 68 (16 Suppl 2): S23–36. doi:10.1212/01.wnl.0000259404.51352.7f. PMID 17438235.
  15. ↑ MUN. 11 Mar 2009.
  16. ↑ TN06 PS19
  17. ↑ Wenning, GK.; Stefanova, N.; Jellinger, KA.; Poewe, W.; Schlossmacher, MG. (Sep 2008). "Multiple system atrophy: a primary oligodendrogliopathy.". Ann Neurol 64 (3): 239-46. doi:10.1002/ana.21465. PMID 18825660.
  18. ↑ Uversky, VN. (Oct 2008). "Alpha-synuclein misfolding and neurodegenerative diseases.". Curr Protein Pept Sci 9 (5): 507-40. PMID 18855701.
  19. ↑ Kumar P, Kalonia H, Kumar A (2010). "Huntington's disease: pathogenesis to animal models". Pharmacol Rep 62 (1): 1–14. PMID 20360611.
  20. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/NeuroTest/Q07-Ans.htm. Accessed on: 29 October 2010.
  21. ↑ 21.0 21.1 http://www.ninds.nih.gov/disorders/joubert/joubert.htm
  22. ↑ MUN. 16 December 2009.
  23. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/neurotest/Q03-Ans.htm. Accessed on: 26 October 2010.
  24. ↑ URL: http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html. Accessed on: 12 July 2010.
  25. ↑ URL: 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. Accessed on: 31 October 2010.
  26. ↑ URL: http://library.med.utah.edu/kw/ms/path.html. Accessed on: 12 July 2010.
  27. ↑ URL: http://library.med.utah.edu/kw/ms/path.html. Accessed on: 12 July 2010.
  28. ↑ Tikka, S.; Mykkänen, K.; Ruchoux, MM.; Bergholm, R.; Junna, M.; Pöyhönen, M.; Yki-Järvinen, H.; Joutel, A. et al. (Apr 2009). "Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients.". Brain 132 (Pt 4): 933-9. doi:10.1093/brain/awn364. PMID 19174371.
  29. ↑ Kalaria, RN.; Viitanen, M.; Kalimo, H.; Dichgans, M.; Tabira, T. (Nov 2004). "The pathogenesis of CADASIL: an update.". J Neurol Sci 226 (1-2): 35-9. doi:10.1016/j.jns.2004.09.008. PMID 15537516.
  30. ↑ 30.0 30.1 Watts JC, Balachandran A, Westaway D (March 2006). "The expanding universe of prion diseases". PLoS Pathog. 2 (3): e26. doi:10.1371/journal.ppat.0020026. PMC 1434791. PMID 16609731. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1434791/.
  31. ↑ Burton, Julian L.; Rutty, Guy N. (2010). The Hospital Autopsy A Manual of Fundamental Autopsy Practice (3rd ed.). Oxford University Press. pp. 83. ISBN 978-0340965146.
  32. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0I002-PQ01-M.htm. Accessed on: 19 October 2010.
  33. ↑ Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 12. ISBN 978-0443069826.

External links

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