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, the spine, the eye, muscle pathologies, neurohistology and neuroanatomy.

Neuroanatomy

Main article: Neuroanatomy

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

Neuroradiology

Enhancing vs. non-enhancing:

  • If it is tumour... enhancing usu. high grade, non-enhancing usu. low grade.

Ring enhancing lesions

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

Ring enhancing lesion (DDx) - mnemonic MAGICAL DR:[2]

Grossing

This is covered in the neuroanatomy article.

Gross pathology

The gross usually useless for arriving at a definitive diagnosis.

Exceptions:[3]

Normal histology

Main article: Neurohistology

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

Histopathology

Neuronal changes

Anoxic neurons

  • AKA red neurons.

Features:

  • Intensely red cytoplasm.
  • Pyknosis = nuclear shrinkage + darker staining.

Images:

Central chromatolysis

Features:[5]

  • Central clearing.
    • Nucleus and Nissl substance are pushed to cell periphery.

DDx:

Images:

Axonal swellings

H&E:

  • Eosinophilic (light pink) - ground glass-like appearance.
  • Shape:
    • Round if sectioned perpendicular to axis of axon.
      • Bound by cell membrane.
      • Large ~ typically 2-4x RBC diameter.
    • Sausage-shaped if cut in along axis.

Images:

IHC
  • APP.

Image:

Glial changes

Astrocyte changes

Reactive astrocytes:

  • Approximately equally-spaced; distance between neighbouring astrocytes is ~2x (or more) the cell size.
  • Well-defined cell border.
  • Eosinophilic cytoplasm with many branching processes.
    • Classically described as "funnel-shaped" in benign astrocytes.[10]
  • Peripheral nucleus.
  • Image: Reactive astrocytes - high mag. (WC).

Alzheimer type II astrocyte:[11]

Creutzfeldt cell:[13]

  • Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
  • Finding associated with demyelinating disease.
  • Image: Crutzfeldt cell (upmc.edu).[14]

Gemistocytic astrocytes:[15]

  • Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:[16]

  • 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):[13]

Reactive change vs. malignancy

Reactive changes vs. malignancy (mnemonic MIMICS):[17]

  • MIcrovesicular pattern.
  • Mitoses.
  • Irregular spacing.
  • Calcifications.
  • Satellitosis, perineuronal.
    • Large "crowds" of glial cells associated with nuclei.

Inflammatory

DDx:

Encephalitis

General

DDx:

  • Viral encephalitis.
  • Paraneoplastic syndromes.
Microscopic

Features:[18]

  • Perivascular inflammation.
  • Microglia.
  • +/-Neuronophagia.
    • Phagocytosis of neurons.[19]
  • +/-Viral cytopathic changes.
  • +/-Perineuronal inflammation.

Notes:

  • Hemorrhage[20] and necrosis - characteristic of HSV encephalitis.

Image:

IHC

IHC stains for:

Architecture

Rosettes

  • Rosette = circular/flower-like arrangement of cells.[22]
  • Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.[22]
  • Flexner-Wintersteiner rosette = rosette with empty centre (donut hole).[22]
  • Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.[22]

Other

  • Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
  • Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.[24]
  • Pseudopalisading - picket fence-like alignment of cells; long axis of cells perpendicular to interface with other structures/cells.
    • Pseudopalisading of tumour cells (around necrotic regions) is seen in glioblastoma.

Note:

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.[25]
    • Image: Lewy body (WC).

Table of inclusions

Feature Appearance Associated disease Comment Image
Grumous bodies
AKA granular bodies 		granular and eosinophilic ~50 micrometers neurodegenerative disease, neuroaxonal dystrophies, aging ?Comment ?Image
Cowdry type 1
AKA Cowdry type A 		eosinophilic & round + halo herpes simplex virus can be confused with
Lewy body, Marinesco body 		?Image
Lewy body round cytoplasmic eosinophilic
body +/- pale halo 		Parkinson disease, dementia with Lewy bodies morphology dependent on
location in brain; +ve for alpha-synuclein,
alpha-B crystallin, ubiquitin 		[1], [2]
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 [3]
Hirano body concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron Alzheimer disease, Pick disease[26] actin crystals, may look like capillaries; location: CA1 of hippocampus [4][27]
Neurofibrillary tangles flame-shaped cytoplasmic thingy
~30 micrometers 		aging, Alzheimer's disease seen with silver stain Schematic[27], [5][28]
Granulovacuolar degeneration cytoplasmic vacuoles 4-5 micrometers ageing, Alzheimer's disease,
Pick's disease 		main found in Ammon horn[26] [6][28]
Pick bodies round, homogenous, intracytoplasmic, ~10 micrometers Pick's disease pyramidal neurons, dentate
granule cells (hippocampus); +ve for tau, tubulin, ubiquitin 		[7]
Bunina body size of Nissl granules, eosinophilic amyotrophic lateral sclerosis (ALS) EM: membrane-bound bodies; ubiquitin +ve [8]

Image collection: Inclusion bodies (photobucket.com).

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.

Glial tumours

Standard work-up:

  • GFAP.
  • p53.
  • Ki-67.

Neuronal

  • Synaptophysin.
  • Chromogranin.

Carcinoma vs. glial tumours

  • AE1/AE3 often +ve in glial tumours (e.g. astrocytomas, oligodendrogliomas); CAM5.2 is usu. -ve in glial tumours.[29]

Others

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

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 (in adults) is glioblastoma which has a horrible prognosis.

Non-tumour

Cerebral hemorrhage

See: Intracranial hematoma for intracranial bleeds

Includes discussion of:

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).[30]
  • Often fatal.[31]

Gross

  • Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).[30]

Image:

Microscopic

Features:

  • RBC extravasation.
  • +/-Hemosiderin-laden macrophages.
  • +/-Ischemic neurons.

Alcohol & CNS

Clinical

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

Pathology

Features:[33]

  • Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex[34] usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.[35]
  • Central pontine myelinolysis (CPM).[36]
    • Just what it sound like - myelin loss in the central pons.
    • Classically associated with rapid correction of hyponatremia.[37]
  • Mammillary body shrinkage.[38]
  • Anterior cerebellar vermis atrophy; weak finding - as also age-related.[39]
    • Vermis atrophy is also seen in schizophrenia.[40]

Marchiafava-Bignami Disease

  • Rare.
  • Demyelination of the corpus callosum.[35]

Wernicke's encephalopathy

General:

  • Due to thiamine deficiency.

Features:

  • Neurons preserved - key.
  • Loss of myelin.
  • Hemorrhage.
  • Spongiosis.
  • Reactive blood vessels.


Common non-specific findings

Meningitis

General

  • Definition: inflammation of the meninges (pia mater, arachnoid membranes, dura mater).

Classic clinical presentation:

  • Neck stiffness.
  • Fever.
  • +/-Headache.
  • +/-Decreased level of consciousness.

Etiology

Bacterial meningitis - most probably cause by age:[41]

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:

Microscopic

Features:

  • Inflammation of the meninges.
  • Infectious meningitis:
    • Microorganisms (bacteria, fungi).

Image:

Cerebral abscess

General

  • May mimic malignancy clinically.

Microscopic

Features:

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

Images:

Neurodegenerative diseases

Main article: Neurodegenerative diseases

This is a hueueuge topic. It is covered its own article and includes a general discussion of dementia.

Epilepsy

Main article: Epilepsy

Cerebrovascular accident

  • Abbreviated CVA.
  • AKA stroke.

General

  • Very common.
  • Leading cause of morbidity and mortality.

Clinical classification:

  1. Hemorrhagic stroke.
  2. Ischemic stroke.

Gross

  • Soft/mushy brain.
  • Older infarcts.
    • A "roof" is present - a thin submeningeal layer is preserved by the CSF.[43]
      • "Roof" is absent in trauma.
    • Cavity - in older infarcts.
  • Laminar necrosis = (thin) chalky line replaces grey mater.[44]
    • AKA pseudolaminar necrosis - as it is not localized to a specific layer of the cortex.[45]

DDx:

Microscopic

Features:

Hypoxic-ischemic encephalopathy

  • Abbreviated HIE.

General

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

Note:

  • Hypoxia = blood decreased oxygen carrying capacity,[46] e.g. anemia.
  • Ischemia = decreased blood flow.[46]
  • Either or both = less oxygen delivery to tissue.

Microscopic

Features:

  • Hippocampal ischemic changes (in adults):
    • 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/resistant.
  • Purkinje cell loss in the cerebellum and Bergmann gliosis.
  • "Anoxic neurons".[47]
    • Shrunken neurons with intensely eosinophilic cytoplasm and pyknotic (shrunken) nuclei.
  • Pseudolaminar necrosis - (uncontrolled) cell death in the cerebral cortex in a band-like pattern,[48] with a relative preservation of cells immediately adjacent to the meninges.

Images:

Notes:

  • Neurons of subiculum in adults - usu. normal (as they are resistant to ischemic changes).

Multiple sclerosis

  • Abbreviated MS.

General

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

Clinical:

  • CSF: oligoclonal bands of immunoglobulin.[51]

Radiologic/Gross

Features:[52]

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

Microscopic

Features:[53]

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

Classification of MS lesions:

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

DDx:

Images:

IHC

  • HAM-56 - macrophages.
  • CD8 - lymphocytes.

Cerebral amyloid angiopathy

General

  • Abbreviated CAA.
  • Disease of the old.
  • Strong association with lobar haemorrhage (bleeds of the cerebellar cortex and cerebral cortex).[54]

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.[55]

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.[56]

Images:

Stains

IHC

  • Abeta-amyloid (AKA beta-amyloid).

Central pontine myelinolysis

  • Abbreviated CPM.
  • AKA pontine myelinolysis.

General

  • Classically in the pons, ergo "pontine" is in the name.
  • Classically midline, ergo "central" is in the name.
    • May occur elsewhere -- known as extrapontine myelinolysis.

Etiology:

  • Rapid correction of hyponatremia.[57]
  • Tacrolimus post-liver transplant.[58]
  • Associated with alcoholism and malnourishment.

Clinical:[59]

  • Decreased level of consciousness - most common.
  • Quadriplegia.
  • Poor prognosis.

Microscopic

Features:[60]

  • Myelin loss.
  • No inflammation.
  • Relative preservation of neurons.

Images:

Vascular malformations

Main article: Vascular malformations

Types:[61]

  1. Arteriovenous malformation.
    • Most important clinically - highest risk of bleeding.
  2. Varix.
    • One large (dilated) vein.
  3. Venous angioma.
    • Many small veins.
  4. Caverous malformation.
    • Vessels are back-to-back (no intervening parenchyma).

Also see: Sturge-Weber syndrome.

Cysts

General

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

List of cysts

  • Colloid cyst.
    • Columnar epithelium.
  • Arachnoid cyst - considered precursor of meningioma.
  • Dermoid cyst.
    • Skin + adnexal structures.
    • ... think of ovarian dermoid.
  • Epidermoid cyst.
  • Choriod cyst.
  • Neuroenteric cyst.
    • Foregut cyst with connection to dura.[62]
      • Gastrointestinal tract epithelium.
      • Usually seen with vertebral anomalies.
  • Epithelial cyst.
  • Others.

Colloid cyst

General

Classic presentation:[63]

Gross

  • Classically in the third ventricle.

Microscopic

Features:[65]

  • Simple epithelium with ciliated cells and goblet cells.

Images:

Paediatric pathology

Kernicterus

General

  • Due to hyperbilirubinemia.[66]

Gross

  • Yellow staining of the basal ganglia.[67]

Note:

  • May not be specific.[66]

Image:

Joubert syndrome

  • Malformation of the cerebellar vermis.[68]

Epidemiology

  • Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.[68]

Weird stuff

Acute disseminated encephalomyelitis

  • Abbreviated ADEM.

General

  • Thought to be autoimmune; often associated with/preceded by by viral illness.[69]
  • May mimic multiple sclerosis.

Treatment:

  • Steroids.
  • Plasmapheresis.

Diagnosis:

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

An acute form exists known as acute hemorrhagic leukoencephalitis[70] (AKA acute necrotizing hemorrhagic encephalomyelitis).

Microscopic

Features:[71]

  • Myelin loss with sparing of axons.
  • Inflammation:
    • Early: neutrophils.
    • Late: mononuclear cells (lymphocytes, plasma cells).
  • Lipid-laden macrophages.

DDx:

  • Multiple sclerosis.
    • Age of the lesions differ.
  • Acute necrotizing hemorrhagic encephalomyelitis (ANHE) - if one considers this a separate entity.
  • Acute necrotizing encephalopathy.[72]

Neuromyelitis optica

  • Abbreviated NMO.

General

  • Rare autoimmune disease - once considered a variant of multiple sclerosis.
    • Autoantibodies directed at aquaporin-4.[73]

Diagnosis:

  • NMO-IgG.

Clinical - preferentially:

  • Eye (optic neuritis).
  • Spinal cord (myelitis).

Microscopic

Features:

  • Inflammation - lymphocytes, macrophages.
  • Reactive astrocytes.

Images:

IHC

  • Mixed lymphocyte population with CD3 > CD20.
  • Aquaporin-4 loss.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

  • Commonly abbreviated CADASIL.

General

  • Autosomal dominant disorder - as the name implies.[74]
  • Causes strokes in 40-50 year-old.
  • Cerebral microbleeds - common.
  • Characteristic MRI findings - present in asymptomatic individuals with mutation.
  • Increased risk of myocardial infarction.[76]

Note:

  • There is also an autosomal recessive form - CARASIL.[77]

Etiology

  • Mutation of Notch 3 gene.[78]
    • Diagnosis: proven Notch 3 mutation.

Microscopic

Features:

  • +/-Subcortical infarcts.
    • Patches of (non-myelinated) tissue within the white matter deep to the cortex with abundant macrophages.
  • Blood vessels typically have a basophilic granularity.[79]

IHC

  • Notch 3: smooth muscle and pericytes punctate +ve.[76]

Image: Notch 3 staining in CADASIL (WC).

Notes:

  • No cortical involvement -- this is unlike multiple sclerosis.

DDx:

Skin biopsy diagnosis

  • Can be diagnosed on a skin biopsy.[80]

Electron microscopy

  • Granular osmiophilic material (GOM).

Progressive multifocal leukoencephalopathy

  • Abbreviated PML.

General

  • Caused by JC virus (a type of polyomavirus[81]) in the context of immunodeficiency; usu. in the setting of HIV infection.[82]
    • Approximately 5% of HIV patients develop PML.[82]
    • Virus destroys oligodendrocytes -> demyelination results.[83]
  • Suspected cases are biopsied - unlike other demyelinating diseases.[84]

Gross

  • Multifocal - as the name suggests.

DDx:

Microscopic

Features:[85]

  • Perivascular inflammatory cells.
  • Foamy histiocytes.
  • Abnormal appearing glial cells:[86]
    • Reactive astrocytes.
    • Oligodendrocytes with nuclear enlargement and glassy magenta chromatin - key feature.
    • Atypical mitoses - known as Creutzfeldt cell.

Images:

IHC

See also

References

  1. ↑ MUN. Feb 3, 2009.
  2. ↑ TN2005 NS7.
  3. ↑ R. Kiehl. 8 November 2010.
  4. ↑ 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.
  5. ↑ URL: http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html. Accessed on: 22 December 2010.
  6. ↑ Holland GR (1996). "Experimental trigeminal nerve injury". Crit. Rev. Oral Biol. Med. 7 (3): 237–58. PMID 8909880.
  7. ↑ Piercecchi-Marti MD, Pélissier-Alicot AL, Leonetti G, Tervé JP, Cianfarani F, Pellissier JF (December 2004). "Pellagra: a rare disease observed in a victim of mental and physical abuse". Am J Forensic Med Pathol 25 (4): 342–4. PMID 15577526.
  8. ↑ URL: http://frontalcortex.com/?page=oll&topic=24&qid=602. Accessed on: 3 November 2010.
  9. ↑ Finnie JW, Manavis J, Blumbergs PC, Kuchel TR (November 2000). "Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin". Vet. Pathol. 37 (6): 677–80. PMID 11105962. http://vet.sagepub.com/content/37/6/677.full.
  10. ↑ MUN. 15 November 2010.
  11. ↑ URL: http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html. Accessed on: 2 July 2010.
  12. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 202. ISBN 978-1416002741.
  13. ↑ 13.0 13.1 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.
  14. ↑ URL: http://path.upmc.edu/cases/case336.html. Accessed on: 15 January 2012.
  15. ↑ URL: http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html. Accessed on: 7 November 2010.
  16. ↑ Gray, Francoise; Poirier, Jacques; De Girolami, Umberto (2003). Escourolle and Poirier's Manual of Basic Neuropathology (4th ed.). Churchill Livingstone. pp. 173. ISBN 978-0750674058.
  17. ↑ Weedman Molavi, Diana (2008). The Practice of Surgical Pathology: A Beginner's Guide to the Diagnostic Process (1st ed.). Springer. pp. 254. ISBN 978-0387744858.
  18. ↑ Takei, H.; Wilfong, A.; Malphrus, A.; Yoshor, D.; Hunter, JV.; Armstrong, DL.; Bhattacharjee, MB. (Aug 2010). "Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of the literature.". Neuropathology 30 (4): 381-91. doi:10.1111/j.1440-1789.2009.01079.x. PMID 20051019.
  19. ↑ URL: http://medical-dictionary.thefreedictionary.com/neuronophagia. Accessed on: 11 April 2012.
  20. ↑ Vossough, A.; Zimmerman, RA.; Bilaniuk, LT.; Schwartz, EM. (Apr 2008). "Imaging findings of neonatal herpes simplex virus type 2 encephalitis.". Neuroradiology 50 (4): 355-66. doi:10.1007/s00234-007-0349-3. PMID 18246335.
  21. ↑ URL: http://neuropathology-web.org/chapter5/chapter5dViruses.html. Accessed on: 27 January 2012.
  22. ↑ 22.0 22.1 22.2 22.3 22.4 22.5 Wippold FJ, Perry A (March 2006). "Neuropathology for the neuroradiologist: rosettes and pseudorosettes". AJNR Am J Neuroradiol 27 (3): 488–92. PMID 16551982.
  23. ↑ URL: http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17. Accessed on: 3 December 2010.
  24. ↑ Gray, Francoise; Poirier, Jacques; De Girolami, Umberto (2003). Escourolle and Poirier's Manual of Basic Neuropathology (4th ed.). Churchill Livingstone. pp. 11. ISBN 978-0750674058.
  25. ↑ 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.
  26. ↑ 26.0 26.1 Gray, Francoise; Poirier, Jacques; De Girolami, Umberto (2003). Escourolle and Poirier's Manual of Basic Neuropathology (4th ed.). Churchill Livingstone. pp. 5. ISBN 978-0750674058.
  27. ↑ 27.0 27.1 URL: http://www.pakmed.net/academic/age/alz/alz030.htm. Accessed on: 12 November 2010.
  28. ↑ 28.0 28.1 URL: http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm. Accessed on: 13 November 2010.
  29. ↑ 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.
  30. ↑ 30.0 30.1 Parizel, PM.; Makkat, S.; Jorens, PG.; Ozsarlak, O.; Cras, P.; Van Goethem, JW.; van den Hauwe, L.; Verlooy, J. et al. (Jan 2002). "Brainstem hemorrhage in descending transtentorial herniation (Duret hemorrhage).". Intensive Care Med 28 (1): 85-8. doi:10.1007/s00134-001-1160-y. PMID 11819006.
  31. ↑ Fujimoto, Y.; Aguiar, PH.; Freitas, AB.; de Andrade, AF.; Marino Júnior, R. (Oct 2000). "Recovery from Duret hemorrhage: a rare complication after craniotomy--case report.". Neurol Med Chir (Tokyo) 40 (10): 508-10. PMID 11098635.
  32. ↑ URL: http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html. Accessed on: 4 December 2011.
  33. ↑ http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract
  34. ↑ URL: http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939. Accessed on: 22 September 2010.
  35. ↑ 35.0 35.1 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.
  36. ↑ Campbell MC (2010). "Hyponatremia and central pontine myelinolysis as a result of beer potomania: a case report". Prim Care Companion J Clin Psychiatry 12 (4). doi:10.4088/PCC.09l00936ecr. PMC 2983455. PMID 21085565. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2983455/.
  37. ↑ Bernsen HJ, Prick MJ (September 1999). "Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia". Acta Neurol Belg 99 (3): 189–93. PMID 10544728.
  38. ↑ 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.
  39. ↑ Torvik A (1987). "Brain lesions in alcoholics: neuropathological observations". Acta Med. Scand. Suppl. 717: 47–54. PMID 3478969.
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