Difference between revisions of "Neuropathology"

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====Encephalitis====
====Encephalitis====
see also:
* [[Viruses]]
* [[Microorganisms]]
=====General=====
=====General=====
DDx:
DDx:
*Viral encephalitis.
*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.
*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=====
=====Gross=====
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*Parasites, e.g. [[toxoplasma]].
*Parasites, e.g. [[toxoplasma]].
*[[Fungi]], e.g. PASD.
*[[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===
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**[[Ependymomblastoma]]s.
**[[Ependymomblastoma]]s.
**[[Medulloepithelioma]]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>
<gallery>
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</gallery>
</gallery>


====Other====
====Other important histological features====
*Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
*Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
**Key feature: variable thickness; helps separate from RBCs.
**Key feature: variable thickness; helps separate from RBCs.
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Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear (WC/AFIP)
Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear (WC/AFIP)
</gallery>
</gallery>
*Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.<ref>{{Ref MBNP|11}}</ref>
*Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in [[astrocyte]]s.<ref>{{Ref MBNP|11}}</ref>
**Image: [Image:Pilocytic_Micro.jpg EGBs (WC/AFIP)].
<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 - 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]].  
**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:  
Note:  
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=Brain tumours=
=Brain tumours=
{{main|Neuropathology tumours}}
{{main|Neuropathology tumours}}
Tumours are a big part of neuropathology.  The most common brain tumour (in adults) is a metastasis.  The most common primary tumour (in adults) is glioblastoma which has a horrible prognosis.
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=
=Non-tumour=
==Cerebral hemorrhage==
==Vascular disorders==
===Cerebral hemorrhage===
:See: ''[[Intracranial hematoma]]'' for intracranial bleeds
:See: ''[[Intracranial hematoma]]'' for intracranial bleeds


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*[[Intracerebral hematoma]]s.
*[[Intracerebral hematoma]]s.


==Duret hematoma==
===Duret hematoma===
*[[AKA]] Duret hemorrhage.
*[[AKA]] Duret hemorrhage.
===General===
====General====
*Bleed in the upper brainstem (midbrain and pons).
*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>
**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>
*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===
====Gross====
*Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).<ref name=pmid11819006/>
*Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).<ref name=pmid11819006/>


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*[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>
*[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===
====Microscopic====
Features:
Features:
*RBC extravasation.  
*RBC extravasation.  
*+/-Hemosiderin-laden macrophages.
*+/-Hemosiderin-laden macrophages.
*+/-Ischemic neurons.
*+/-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}}
===Hypoxic-ischemic encephalopathy===
*Abbreviated ''HIE''.
{{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).


==Alcohol & CNS==
==Alcohol & CNS==
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! Protein
! Protein
! Cells
! Cells
! Cytopathology
|-
|-
| Bacterial, acute
| Bacterial, acute
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| high
| high
| neutrophils
| neutrophils
| [[File:Purulent_CSF.jpg|100px|center|]][[CSF_cytopathology#Acute_bacterial_meningitis|Cytophathology]]
|-
|-
| Viral
| Viral
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| slight elevation
| slight elevation
| lymphocytes
| lymphocytes
| [[CSF_cytopathology#Viral_meningitis|Cytophathology]]
|}
|}


====Etiology====
====Etiology====
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|-
|-
| Neonate
| Neonate
| ''Escherichia coli'', Group B Streptococcus
| ''Escherichia coli'', ''Group B Streptococcus''
|-
|-
| Infants, children
| Infants, children
Line 581: Line 766:
====Image====
====Image====
<gallery>
<gallery>
Image:Streptococcus_pneumoniae_meningitis,_gross_pathology_33_lores.jpg | Meningitis. (WC)
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>
</gallery>


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


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


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


==Hypoxic-ischemic encephalopathy==
*Type I FCD (focal)
*Abbreviated ''HIE''.
**Ia: Abnormal radial cortical lamination.
{{Main|Hypoxic-ischemic encephalopathy}}
**Ib: Abnormal tangential cortical lamination.
**Ic: Abnormal radial and tangential cortical lamination.


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


==Cerebral amyloid angiopathy==
*Type II FCD (focal)
===General===
**IIa: Presence of dysmorphic neurons.
*Abbreviated ''CAA''.
**IIb: Presence of dysmorphic neurons and balloon cells.
*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===
*Type III FCD (associated with other lesion)
*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>
**IIIa: FCD associated with [[Epilepsy#Hippocampal_sclerosis|hippocampal sclerosis]].
**IIIb: FCD adjacent to a brain tumor.
**IIIc: FCD adjacent to vascular malformation.
**IIIc: FCD associated with previous injury (trauma, inflammation...).


===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>
<gallery>
Image:Cerebral_amyloid_angiopathy_-_very_high_mag.jpg |CAA - congo red - very high mag. (WC)
File:FCDIIa dysmorphic neurons HE.jpg|Dysmorphic neurons in FCD (HE)
Image:Cerebral_amyloid_angiopathy_-_low_mag.jpg |CAA - congo red - low mag. (WC)
File:FCDIIa neuronal heterotopia neun.jpg|Heterotopic neurons (NeuN)
Image:Cerebral_amyloid_angiopathy_-2b-_amyloid_beta_-_high_mag.jpg |CAA - beta-amyloid - high mag. (WC)
</gallery>
</gallery>
===Stains===
*[[Congo red]].


===IHC===
===Hamartia===
*Abeta-amyloid (AKA beta-amyloid).
* Small collection of ectopic glioneuronal cells.
**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.
 
==Demyelination==
 
===Multiple sclerosis===
*Abbreviated ''MS''.
{{Main|Multiple sclerosis}}
 
===Osmotic demyelination syndrome===
{{Main|Osmotic demyelination syndrome}}
*Previously known as ''central pontine myelinolysis'' (abbreviated ''CPM'').
 
===Acute disseminated encephalomyelitis===
*Abbreviated ''ADEM''.
{{Main|Acute disseminated encephalomyelitis}}
 
===Neuromyelitis optica===
*Abbreviated ''NMO''.


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


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


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


Images:
Images:
*[http://neuropathology-web.org/chapter6/images6/6-9l.jpg CPM (neuropathology-web.org)].<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*[http://path.upmc.edu/cases/case637.html Neuromyelitis optica - several images (upmc.edu)].
*[http://dartmed.dartmouth.edu/spring09/html/virtual_microscopy_we/ CPM (dartmouth.edu)].
 
IHC:
*Mixed lymphocyte population with CD3 > CD20.
*Aquaporin-4 loss.
 
===Progressive multifocal leukoencephalopathy===
*Abbreviated ''PML''.
{{Main|Progressive multifocal leukoencephalopathy}}


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


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


=Cysts=
=Cysts=
Line 732: Line 934:
***Usually seen with vertebral anomalies.  
***Usually seen with vertebral anomalies.  
*Epithelial cyst.
*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.
*Others.


Line 788: Line 995:
===Epidemiology===
===Epidemiology===
*Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.<ref name=ninds_joubert/>
*Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.<ref name=ninds_joubert/>
=Weird stuff=
==Acute disseminated encephalomyelitis==
*Abbreviated ''ADEM''.
{{Main|Acute disseminated encephalomyelitis}}
==Neuromyelitis optica==
*Abbreviated ''NMO''.
===General===
*Rare autoimmune disease - once considered a variant of [[multiple sclerosis]].
**Autoantibodies directed at aquaporin-4.<ref name=pmid22087205>{{Cite journal  | last1 = Kim | first1 = W. | last2 = Kim | first2 = SH. | last3 = Kim | first3 = HJ. | title = New insights into neuromyelitis optica. | journal = J Clin Neurol | volume = 7 | issue = 3 | pages = 115-27 | month = Sep | year = 2011 | doi = 10.3988/jcn.2011.7.3.115 | PMID = 22087205 }}</ref>
Diagnosis:
*NMO-IgG.
Clinical - preferentially:
*Eye (optic neuritis).
*Spinal cord (myelitis).
===Microscopic===
Features:
*Inflammation - lymphocytes, macrophages.
*Reactive astrocytes.
Images:
*[http://path.upmc.edu/cases/case637.html Neuromyelitis optica - several images (upmc.edu)].
===IHC===
*Mixed lymphocyte population with CD3 > CD20.
*Aquaporin-4 loss.
==Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy==
*Commonly abbreviated ''CADASIL''.
{{Main|Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy}}
==Progressive multifocal leukoencephalopathy==
*Abbreviated ''PML''.
{{Main|Progressive multifocal leukoencephalopathy}}


=See also=
=See also=

Latest revision as of 17:17, 25 March 2021

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

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

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

Neuroanatomy

Main article: 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

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

  • Anoxic neurons (WC)

  • Neurons in an acute stroke. (WC)

www:

Central chromatolysis

Features:[6]

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

DDx:

Images

  • Central chromatolysis - intermed. mag. (WC)

  • Central chromatolysis - NF stain - very high mag. (WC)

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.

  • Reactive astrocytes - high mag. (WC)

Alzheimer type II astrocyte:[12]

  • Alzheimer type II astrocytes. (WC)

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.

  • Bergmann gliosis - intermed. mag. (WC)

  • Bergmann gliosis - high mag. (WC)

  • Bergmann gliosis due to compression by metastasis - intermed mag. (WC)

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:

  • Intraoperative appearance of a lymphocytic encephalitis (WC/jensflorian)

  • Perivascular inflammation in a lymphocytic encephalitis (WC/jensflorian)

  • Hemorrhage in HSV encephalitis (WC/jensflorian)

  • HSV encephalitis, higher magnification (WC/jensflorian)

  • Neonatal brain with migration disturbances due to CMV infection (WC/jensflorian)

  • Neuronal nuclear inclusions in a neonatal CMV infection (WC/jensflorian)

  • Rabies encephalitis (CDC.gov)

  • Negri bodies in Purkinje cells (CDC.gov)

Vasculitis

DDx Cerebral vasculitis / angiitis:

  • Beta-amyloid related angitis, HE (WC)

  • Beta-amyloid related angiitis, abeta IHC (WC)

  • Giant cell arteritis, HE (WC)

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

  • Homer-Wright rosettes (WC).

  • Neurocytic rosettes (WC).

  • Perivascular pseudorosette (WC).

  • Multilayered rosettes (WC).

  • Ependymoblastous rosettes (WC/Marvin101).

  • True ependymal rosettes and pseudorosettes (WC).

  • Radial (cartwheel) profiles (WC).

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.

  • Rosenthal fibres. (WP)

  • Rosenthal fibres - smear (WC/AFIP)

  • Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.[30]

  • Eosinophilic granular bodies in pilocytic astrocytoma smear (WC/AFIP)

  • Eosinophilic granular body in a pleomorphic xanthoastrocytoma (WC/jensflorian)

  • 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.

  • Pseudopalisading necrosis in a glioblastoma (WC/jensflorian)

Note:

Inclusion bodies

  • Negri bodies.
    • Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
    • Rabies.

  • Negri bodies. (WC/CDC)

  • Owl eye inclusions.
    • Basiopilic neuronal inclusions in enlarged cells, typically seen in CMV encephalitis

  • Owl eye inclusions

  • Lewy bodies.
    • Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.[32]

  • Lewy body. (WC)

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

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.
  • 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

Main article: 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 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

  • CAA - congo red - very high mag. (WC)

  • CAA - congo red - low mag. (WC)

  • CAA - beta-amyloid - high mag. (WC)

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

Main article: Vascular malformations

Types:[49]

Also see: Sturge-Weber syndrome.

Atherosclerosis

Main article: Vascular_disease#Atherosclerosis
  • Intracranial atherosclerosis most common at circle of Willis.
  • Macroscopic yellow discoloration.
  • Luminal stenosis and eccentric intimal thickening.

  • Plaque of the carotid bifurcation (Ed Uthman).

Other large arterial diseases

Microangiopathy

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

Other causes:

Main article: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Hypoxic-ischemic encephalopathy

  • Abbreviated HIE.
Main article: Hypoxic-ischemic encephalopathy
    • Hypoxia: reduction in oxygen supply or utilization.
    • Ischemia: reduction in blood supply.

Cerebrovascular accident

  • Abbreviated CVA.
  • AKA stroke.
Main article: 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).


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
Purulent CSF.jpg
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

  • Streptococcus Meningitis. (WC/Dr. Edwin P. Ewing, Jr.)

  • Hemophilus influenza Meningitis. (WC/CDC)

  • Pneumococcus Meningitis. (WC/Dr. Yale Rosen)

  • Bacterial Meningitis MRI (WC/MBq)

Microscopic

Features:

Main DDx:

Image

  • Bacterial meningitis. (WC/Marvin101)

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 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

Main article: 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...).


  • Dysmorphic neurons in FCD (HE)

  • Heterotopic neurons (NeuN)

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.
Main article: Multiple sclerosis

Osmotic demyelination syndrome

Main article: Osmotic demyelination syndrome
  • Previously known as central pontine myelinolysis (abbreviated CPM).

Acute disseminated encephalomyelitis

  • Abbreviated ADEM.
Main article: Acute disseminated encephalomyelitis

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.
Main article: Progressive multifocal leukoencephalopathy


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

  • Colloid cyst at autopsy. (Shaktawat et al.[70])

www:

Microscopic

Features:[71]

  • Simple epithelium with ciliated cells and goblet cells.

Images

  • Colloid cyst. (WC)

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

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  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.
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  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.
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  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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