Neuropathology

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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.

Gross image showing changes of a stroke. (WC/Marvin 101)

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

Neuroanatomy

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

Neuroradiology

Key factors to consider in evaluation:

  1. Location.
  2. Number of lesions - single versus multiple.
  3. Cystic versus solid lesion.
  4. Enhancement.

Lesion location

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

Cortical lesions (gray matter):

Cortical-subcortical junction:

Subcortical lesions (white matter):

Deep gray matter lesions (e.g. basal ganglia):

Cerebellar lesions:

Intraventricular lesions:

Suprasellar (above the pituitary):

Number of lesions

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

Cystic vs. solid lesions

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

Enhancing vs. non-enhancing:

  • In adults, enhancing generally = high grade.
  • In pediatrics, it often depends on the pattern.

Two main patterns to be mindful of -- ring enhancing lesions, and cystic lesions with a mural nodule.

Ring enhancing lesions

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

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

Cyst with enhancing mural nodule

  • hemangioblastoma (#1 in adults)
  • pilocytic astrocytoma (#1 in peds)
  • pleomorphic xanthoastrocytoma
  • ganglioglioma

Grossing

This is covered in the neuroanatomy article.

Gross pathology

The gross usually useless for arriving at a definitive diagnosis.

Exceptions:[3]

Normal histology

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

www:

Central chromatolysis

Features:[6]

  • 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.[11]
  • Peripheral nucleus.

Alzheimer type II astrocyte:[12]

Creutzfeldt cell:[14]

  • Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
  • Finding associated with demyelinating disease.
  • Image: Crutzfeldt cell (upmc.edu).[15]

Gemistocytic astrocytes:[16]

  • Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:[17]

  • 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):[14]

  • Thin layer of cells (2-3 cells) with open nuclei that are larger than granular cell layer nuclei; seen with Purkinje cell loss.

Image:

Reactive change vs. malignancy

Reactive changes vs. malignancy (mnemonic MIMICS):[18]

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

Inflammatory

DDx:

Encephalitis

see also:

General

DDx:

  • Viral encephalitis (Neurotrophic viruses):[19]
    • 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).
    • 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
  • Septic metastatic encephalitis
    • microabscesses, local astrogliosis, two or more granulocytic infiltrates without relation to vessel.[20]
  • Septic embolic encephalitis
    • Embolic endocarditis, Stroke-like lesions.[21]
  • Non-purulent bacterial encephalitis
Gross
  • Frontal and temporal lobe - most common for HSV encephalitis.[22]
Microscopic

Features:[23]

  • Perivascular inflammation.
  • Microglia.
  • +/-Neuronophagia.
    • Phagocytosis of neurons.[24]
  • +/-Viral cytopathic changes.
  • +/-Perineuronal inflammation.

Notes:

  • Hemorrhage[25] and necrosis - characteristic of HSV encephalitis.

Image:

IHC

IHC stains for:

Vasculitis

DDx Cerebral vasculitis / angiitis:

Architecture

Rosettes

  • Rosette = circular/flower-like arrangement of cells.[27]
  • Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.[27]
  • Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.[27]
  • Radial (cartwheel) profiles = neoplastic cells anchoring to stromal vessels, shorter processes than in ependymal pseudorosettes

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.
  • Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.[30]
  • 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.
  • Owl eye inclusions.
    • Basiopilic neuronal inclusions in enlarged cells, typically seen in CMV encephalitis
  • Lewy bodies.
    • Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.[32]

Table of inclusions

Feature Appearance Associated disease Comment Image
Grumose bodies
AKA granular bodies
granular and eosinophilic ~50 micrometers neurodegenerative disease, neuroaxonal dystrophies, aging ?Comment ?Image
Cowdry type 1
AKA Cowdry type A
eosinophilic & round + halo herpes simplex virus can be confused with
Lewy body, Marinesco body
?Image
Lewy body round cytoplasmic eosinophilic
body +/- pale halo
Parkinson disease, dementia with Lewy bodies morphology dependent on
location in brain; +ve for alpha-synuclein,
alpha-B crystallin, ubiquitin
Lewy Koerperchen.JPG
, [1]
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
Rabies encephalitis Negri bodies PHIL 3377 lores.jpg
Hirano body concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron Alzheimer disease, Pick disease[33] actin crystals, may look like capillaries; location: CA1 of hippocampus [2][34]
Neurofibrillary tangles flame-shaped cytoplasmic thingy
~30 micrometers
aging, Alzheimer's disease seen with silver stain Schematic[34], [3][35]
Granulovacuolar degeneration cytoplasmic vacuoles 4-5 micrometers ageing, Alzheimer's disease,
Pick's disease
main found in Ammon horn[33] [4][35]
Pick bodies round, homogenous, intracytoplasmic, ~10 micrometers Pick's disease pyramidal neurons, dentate
granule cells (hippocampus); +ve for tau, tubulin, ubiquitin
[5]
Bunina body size of Nissl granules, eosinophilic amyotrophic lateral sclerosis (ALS) EM: membrane-bound bodies; ubiquitin +ve [6]

Image collection: Inclusion bodies (photobucket.com).

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. [36]
  • Ki-67 (MIB-1).

Useful additional markers:

  • IDH1(R132H) in Astrocytic/Oligodendroglial tumors. [37]
  • ATRX in mixed gliomas. [38]
  • EMA in Ependymal tumors. [39]
  • OLIG-2 usually -ve in Ependymomas. [40][41]

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.[42]

Others

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

Brain 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 gliomas. 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:

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).[43]
  • Often fatal.[44]

Gross

  • Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).[43]

Image:

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).[46]

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.[47]

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.[48]

Images

Stains

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

Types:[49]

Also see: Sturge-Weber syndrome.

Atherosclerosis

  • Intracranial atherosclerosis most common at circle of Willis.
  • Macroscopic yellow discoloration.
  • Luminal stenosis and eccentric intimal thickening.

Other large arterial diseases

Microangiopathy

  • Defined as Small vessel disease (<300µm in transverse section).
  • Includes atherosclerosis and cerebral amyloid angiopathy.

Other causes:

Hypoxic-ischemic encephalopathy

  • Abbreviated HIE.
    • Hypoxia: reduction in oxygen supply or utilization.
    • Ischemia: reduction in blood supply.

Cerebrovascular accident

  • Abbreviated CVA.
  • AKA stroke.
  • 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).


Alcohol & CNS

Clinical

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

Pathology

Features:[50]

  • Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex[51] usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.[52]
  • Central pontine myelinolysis (CPM).[53]
    • Just what it sound like - myelin loss in the central pons.
    • Classically associated with rapid correction of hyponatremia.[54]
  • Mammillary body shrinkage.[55]
  • Anterior cerebellar vermis atrophy; weak finding - as also age-related.[56]
    • Vermis atrophy is also seen in schizophrenia.[57]

Marchiafava-Bignami Disease

  • Rare.
  • Demyelination of the corpus callosum.[52]

Wernicke's encephalopathy

General:

  • Due to thiamine deficiency.

Features:[58]

  • Neurons of mammillary bodies preserved - key.
  • Loss of myelin.
  • Hemorrhage.
  • Edema.
  • Reactive blood vessels.

Note:

  • The thalamus and inferior olives show neuronal loss.[58]

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.

CSF findings:

Type Glucose Protein Cells Cytopathology
Bacterial, acute low high neutrophils Cytophathology
Viral normal slight elevation lymphocytes Cytophathology


Etiology

Bacterial meningitis - most probably cause by age:[59]

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:

Main DDx:

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

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.[61]

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.[62]

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 [63](based on previous classification by Palmini 2004):


  • Type I FCD (focal)
    • Ia: Abnormal radial cortical lamination.
    • Ib: Abnormal tangential cortical lamination.
    • Ic: Abnormal radial and tangential cortical lamination.


  • Type II FCD (focal)
    • IIa: Presence of dysmorphic neurons.
    • IIb: Presence of dysmorphic neurons and balloon cells.


  • Type III FCD (associated with other lesion)
    • IIIa: FCD associated with hippocampal sclerosis.
    • IIIb: FCD adjacent to a brain tumor.
    • IIIc: FCD adjacent to vascular malformation.
    • IIIc: FCD associated with previous injury (trauma, inflammation...).


Hamartia

  • Small collection of ectopic glioneuronal cells.
    • Morpholology resembling oligodendroglial-like cells. [64]
  • Mostly amygdala, less common in hippocampus or temporal lobe.
  • Can coexist with focal cortical dysplasia.

Demyelination

Multiple sclerosis

  • Abbreviated MS.

Osmotic demyelination syndrome

  • Previously known as central pontine myelinolysis (abbreviated CPM).

Acute disseminated encephalomyelitis

  • Abbreviated ADEM.

Neuromyelitis optica

  • Abbreviated NMO.

General:

  • Rare autoimmune disease - once considered a variant of multiple sclerosis.
    • Autoantibodies directed at aquaporin-4.[65]

Diagnosis:

  • NMO-IgG.

Clinical - preferentially:

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

Microscopic:

  • Inflammation - lymphocytes, macrophages.
  • Reactive astrocytes.

Images:

IHC:

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

Progressive multifocal leukoencephalopathy

  • Abbreviated PML.


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.
  • Choroid plexus cyst.
  • Neuroenteric cyst.
    • Foregut cyst with connection to dura.[66]
      • Gastrointestinal tract epithelium.
      • Usually seen with vertebral anomalies.
  • Epithelial cyst.
  • Cyst with a mural nodule tumor of the brain.
  • Others.

Colloid cyst

General

Classic presentation:[68]

Gross

  • Fluid filled cyst - classically in the third ventricle.

Images

www:

Microscopic

Features:[71]

  • Simple epithelium with ciliated cells and goblet cells.

Images

www:

Paediatric pathology

Kernicterus

General

  • Due to hyperbilirubinemia.[72]

Gross

  • Yellow staining:[73]
    • Basal ganglia.[74]
    • Hippocampus.[75]
    • Subthalamic nucleus.

Note:

  • May not be specific.[72]

Image:

Microscopic

Features - similar to HIE:[73]

  • +/-Red neurons.
  • +/-Gliosis.

Joubert syndrome

  • Malformation of the cerebellar vermis.[76]

Epidemiology

  • Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.[76]

See also

References

  1. MUN. Feb 3, 2009.
  2. Yeung, J.C.; Leonard, Blair J. N. (2005). The Toronto Notes 2005 - Review for the MCCQE and Comprehensive Medical Reference (2005 ed.). The Toronto Notes Inc. for Medical Students Inc.. pp. NS7. ISBN 978-0968592854.
  3. R. Kiehl. 8 November 2010.
  4. URL: http://neuropathology-web.org/chapter2/chapter2aHIE.html. Accessed on: 10 December 2014.
  5. 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.
  6. URL: http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html. Accessed on: 22 December 2010.
  7. Holland GR (1996). "Experimental trigeminal nerve injury". Crit. Rev. Oral Biol. Med. 7 (3): 237–58. PMID 8909880.
  8. 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.
  9. URL: http://frontalcortex.com/?page=oll&topic=24&qid=602. Accessed on: 3 November 2010.
  10. 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.
  11. MUN. 15 November 2010.
  12. URL: http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html. Accessed on: 2 July 2010.
  13. Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 202. ISBN 978-1416002741.
  14. 14.0 14.1 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.
  15. URL: http://path.upmc.edu/cases/case336.html. Accessed on: 15 January 2012.
  16. URL: http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html. Accessed on: 7 November 2010.
  17. 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.
  18. 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.
  19. Ludlow, M.; Kortekaas, J.; Herden, C.; Hoffmann, B.; Tappe, D.; Trebst, C.; Griffin, DE.; Brindle, HE. et al. (Feb 2016). "Neurotropic virus infections as the cause of immediate and delayed neuropathology.". Acta Neuropathol 131 (2): 159-84. doi:10.1007/s00401-015-1511-3. PMID 26659576.
  20. Tauber, SC.; Bunkowski, S.; Brück, W.; Nau, R. (Dec 2011). "Septic metastatic encephalitis: coexistence of brain damage and repair.". Neuropathol Appl Neurobiol 37 (7): 768-76. doi:10.1111/j.1365-2990.2011.01196.x. PMID 21696418.
  21. Bitsch, A.; Nau, R.; Hilgers, RA.; Verheggen, R.; Werner, G.; Prange, HW. (Oct 1996). "Focal neurologic deficits in infective endocarditis and other septic diseases.". Acta Neurol Scand 94 (4): 279-86. PMID 8937541.
  22. Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 416 Q47. ISBN 978-1416025887.
  23. 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.
  24. URL: http://medical-dictionary.thefreedictionary.com/neuronophagia. Accessed on: 11 April 2012.
  25. 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.
  26. URL: http://neuropathology-web.org/chapter5/chapter5dViruses.html. Accessed on: 27 January 2012.
  27. 27.0 27.1 27.2 27.3 27.4 27.5 Wippold FJ, Perry A (March 2006). "Neuropathology for the neuroradiologist: rosettes and pseudorosettes". AJNR Am J Neuroradiol 27 (3): 488–92. PMID 16551982.
  28. URL: http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17. Accessed on: 3 December 2010.
  29. Liverman, C.; Mafra, M.; Chuang, SS.; Shivane, A.; Chakrabarty, A.; Highley, R.; Hilton, DA.; Byrne, NP. et al. (Aug 2015). "A clinicopathologic study of 11 rosette-forming meningiomas: a rare and potentially confusing pattern.". Acta Neuropathol 130 (2): 311-3. doi:10.1007/s00401-015-1456-6. PMID 26106026.
  30. 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.
  31. Rossi, ML.; Jones, NR.; Candy, E.; Nicoll, JA.; Compton, JS.; Hughes, JT.; Esiri, MM.; Moss, TH. et al. (1989). "The mononuclear cell infiltrate compared with survival in high-grade astrocytomas.". Acta Neuropathol 78 (2): 189-93. PMID 2750489.
  32. 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.
  33. 33.0 33.1 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.
  34. 34.0 34.1 URL: http://www.pakmed.net/academic/age/alz/alz030.htm. Accessed on: 12 November 2010.
  35. 35.0 35.1 URL: http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm. Accessed on: 13 November 2010.
  36. Blümcke, I.; Müller, S.; Buslei, R.; Riederer, BM.; Wiestler, OD. (Aug 2004). "Microtubule-associated protein-2 immunoreactivity: a useful tool in the differential diagnosis of low-grade neuroepithelial tumors.". Acta Neuropathol 108 (2): 89-96. doi:10.1007/s00401-004-0873-8. PMID 15146346.
  37. Paulus, W. (Nov 2009). "GFAP, Ki67 and IDH1: perhaps the golden triad of glioma immunohistochemistry.". Acta Neuropathol 118 (5): 603-4. doi:10.1007/s00401-009-0600-6. PMID 19847448.
  38. Reuss, DE.; Sahm, F.; Schrimpf, D.; Wiestler, B.; Capper, D.; Koelsche, C.; Schweizer, L.; Korshunov, A. et al. (Jan 2015). "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.". Acta Neuropathol 129 (1): 133-46. doi:10.1007/s00401-014-1370-3. PMID 25427834.
  39. Hasselblatt, M.; Paulus, W. (Oct 2003). "Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas.". Acta Neuropathol 106 (4): 385-8. doi:10.1007/s00401-003-0752-8. PMID 12898159.
  40. Ishizawa, K.; Komori, T.; Shimada, S.; Hirose, T.. "Olig2 and CD99 are useful negative markers for the diagnosis of brain tumors.". Clin Neuropathol 27 (3): 118-28. PMID 18552083.
  41. Otero, JJ.; Rowitch, D.; Vandenberg, S. (Sep 2011). "OLIG2 is differentially expressed in pediatric astrocytic and in ependymal neoplasms.". J Neurooncol 104 (2): 423-38. doi:10.1007/s11060-010-0509-x. PMID 21193945.
  42. 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.
  43. 43.0 43.1 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.
  44. 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.
  45. URL: http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html. Accessed on: 4 December 2011.
  46. Thanvi B, Robinson T (November 2006). "Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage in older people". Age Ageing 35 (6): 565–71. doi:10.1093/ageing/afl108. PMID 16982664.
  47. Haacke, EM.; DelProposto, ZS.; Chaturvedi, S.; Sehgal, V.; Tenzer, M.; Neelavalli, J.; Kido, D. (Feb 2007). "Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging.". AJNR Am J Neuroradiol 28 (2): 316-7. PMID 17297004.
  48. Schröder, R.; Deckert, M.; Linke, RP. (Mar 2009). "Novel isolated cerebral ALlambda amyloid angiopathy with widespread subcortical distribution and leukoencephalopathy due to atypical monoclonal plasma cell proliferation, and terminal systemic gammopathy.". J Neuropathol Exp Neurol 68 (3): 286-99. doi:10.1097/NEN.0b013e31819a87f9. PMID 19225408.
  49. Prayson RA, Kleinschmidt-DeMasters BK (November 2006). "An algorithmic approach to the brain biopsy--part II". Arch. Pathol. Lab. Med. 130 (11): 1639–48. PMID 17076525.
  50. http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract
  51. URL: http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939. Accessed on: 22 September 2010.
  52. 52.0 52.1 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.
  53. 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/.
  54. 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.
  55. 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.
  56. Torvik A (1987). "Brain lesions in alcoholics: neuropathological observations". Acta Med. Scand. Suppl. 717: 47–54. PMID 3478969.
  57. 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.
  58. 58.0 58.1 Torvik, A.. "Two types of brain lesions in Wernicke's encephalopathy.". Neuropathol Appl Neurobiol 11 (3): 179-90. PMID 3929155.
  59. Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 666-7. ISBN 978-1416054542.
  60. URL: http://pathology.class.kmu.edu.tw/ch01/Slide4.htm. Accessed on: 1 January 2012.
  61. "Genetic Basis of Brain Malformations". Mol Syndromol 7 (4): 220–233. September 2016. doi:10.1159/000448639. PMC 5073505. PMID 27781032. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073505/.
  62. "Mosaic trisomy of chromosome 1q in human brain tissue associates with unilateral polymicrogyria, very early-onset focal epilepsy, and severe developmental delay". Acta Neuropathol 140 (6): 881–891. December 2020. doi:10.1007/s00401-020-02228-5. PMID 32979071.
  63. Blümcke, I.; Aronica, E.; Miyata, H.; Sarnat, HB.; Thom, M.; Roessler, K.; Rydenhag, B.; Jehi, L. et al. (Mar 2016). "International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: A consensus Task Force report from the ILAE Commission on Diagnostic Methods.". Epilepsia 57 (3): 348-58. doi:10.1111/epi.13319. PMID 26839983.
  64. Kasper, BS.; Stefan, H.; Buchfelder, M.; Paulus, W. (Jan 1999). "Temporal lobe microdysgenesis in epilepsy versus control brains.". J Neuropathol Exp Neurol 58 (1): 22-8. PMID 10068310.
  65. Kim, W.; Kim, SH.; Kim, HJ. (Sep 2011). "New insights into neuromyelitis optica.". J Clin Neurol 7 (3): 115-27. doi:10.3988/jcn.2011.7.3.115. PMID 22087205.
  66. URL: http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm. Accessed on: 19 December 2011.
  67. Raz, E.; Zagzag, D.; Saba, L.; Mannelli, L.; Di Paolo, PL.; D'Ambrosio, F.; Knopp, E. (Aug 2012). "Cyst with a mural nodule tumor of the brain.". Cancer Imaging 12: 237-44. doi:10.1102/1470-7330.2012.0028. PMID 22935908.
  68. Spears, RC. (Aug 2004). "Colloid cyst headache.". Curr Pain Headache Rep 8 (4): 297-300. PMID 15228889.
  69. Kava, MP.; Tullu, MS.; Deshmukh, CT.; Shenoy, A.. "Colloid cyst of the third ventricle: a cause of sudden death in a child.". Indian J Cancer 40 (1): 31-3. PMID 14716130.
  70. Shaktawat, SS.; Salman, WD.; Twaij, Z.; Al-Dawoud, A. (2006). "Unexpected death after headache due to a colloid cyst of the third ventricle.". World J Surg Oncol 4: 47. doi:10.1186/1477-7819-4-47. PMID 16867192.
  71. 71.0 71.1 71.2 Armao, D.; Castillo, M.; Chen, H.; Kwock, L. (Sep 2000). "Colloid cyst of the third ventricle: imaging-pathologic correlation.". AJNR Am J Neuroradiol 21 (8): 1470-7. PMID 11003281.
  72. 72.0 72.1 Turkel, SB.; Miller, CA.; Guttenberg, ME.; Moynes, DR.; Godgman, JE. (Mar 1982). "A clinical pathologic reappraisal of kernicterus.". Pediatrics 69 (3): 267-72. PMID 7063283.
  73. 73.0 73.1 URL: http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html. Accessed on: 30 May 2012.
  74. Hansen, TW.; Hervieux, JF.; Orth, J.; Schmorl, CG.; Baumes, JB. (Aug 2000). "Pioneers in the scientific study of neonatal jaundice and kernicterus.". Pediatrics 106 (2): E15. PMID 10920171.
  75. Paksoy, Y.; Koç, H.; Genç, BO.. "Bilateral mesial temporal sclerosis and kernicterus.". J Comput Assist Tomogr 28 (2): 269-72. PMID 15091133.
  76. 76.0 76.1 http://www.ninds.nih.gov/disorders/joubert/joubert.htm

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