Neuropathology Summary ©2010 Mark Tuttle
CNS Injury- Neurons: most susceptible
Hippocampus CA1: exitotoxic
Purkinje cells (cerebellum)
o Red Neurons: acute injury
§ Cells shrink
§ Pyknosis: nucleus shrinks
§ Nucleus disappears
o Subacute injury
§ Cell loss
§ Trans-synaptic degeneration
1:1 ratio
§ Trauma, degenerative disease, Vitamin E deficiency
o Axonal damage
§ Cell body enlargement
§ Axonal swelling
§ Switches from making exogenous proteins (NTs) to endogenous proteins (repair)
o Neuronal inclusions
§ Aging: lipofuscin
§ Herpes infection: Cowdry body
§ Rabies: Negri body
§ CMV: Negri body in nuc/cyt
§ Neurofibrillary: AD, PSP
§ Parkinsons/dementia: Lewy
§ Pick disease: Pick body
- Astrocytes: à Gemistocytic
o Hypertrophy and hyperplasia
o Become vesicular
o Develop prominent nucleoli
o Contain GFAP filament
o “Alzheimers II” glia: liver failure
o Rosenthal fibers
§ Lafora bodies à epilepsy
- Oligodendrocytes
o JC Virus à PML
- Microglia: mesoderm-derived
o Neurophagia: dying neurons
o Nodules: necrosis
o Rod cells
o Synaptic remodeling
- Ependymal cells
o Granulations
o Viral inclusions: / Histology
Eosinophilic cytoplasm
Reactive gliosis
àAstrogliosis
Central chromatolysis Nissl subst (RER) àSER
Numerous stout, ramifying processes, basophilic cytplasm
Heat shock proteins
- Pilocytic astrocytoma
- Chronic gliosis
Filamentous inclusions
Syphilis
CMV / Congenital Brain Malformations
- Week 1: Implantation
- Week 2: Neural Tube Defects (↑α-fetoprotein)
o Anencephaly: No brain AND no cranial vault
o Posterior neuropore defects
§ Myeolomenigniocele
§ Meningiocele
§ Rachichisis (no spinal cord)
§ Spina bifida occulta: common, usually clinically silent
o Encephalocele: Skull failed to close, brain herniated out
o Chiari I:
§ Cerebellar tonsils herniated through foramen magnum
§ Symtoms of CSF obstriciton
§ Syringomyelia (90%)
o Chiari II (Arnold-Chiari Malformation)
§ Hydrocephalus
§ Meningiocele
§ Herniation of vermis & medulla through foramen magnum
§ Widened foramen magnum
§ Small posterior fossa
§ Cervical notch
- Weeks 4-8: Organogenesis
o Holoprosencephaly: Failure to divide hemispheres
§ Spectrum: from cyclopia (bad) to (arrhyinencephaly) olfactory agenesis (benign)
§ Trisomy 13 sometimes, sHH mutation
§ NOT good
o Agenesis of corpus callosum: Can be clinically silent. No cingulated gyrus
o Dandy-Walker
§ Enlarged posterior fossa
§ No cerebellar vermis à Cyst continuous w/Leptomeninges
· Expanded 4th ventricle
- Cell Migration: If less neurons reach neocortexàsimpler folding
o Polymicroglia: Microcephaly (more common)/Macrocephaly. Occcurs in many disorders
o Pachygyria
o Heterotopias: Failed migration of neurons. Can cause seizures. @ ventricles
o Lissencephay (agyria): Looks like normal fetal brain @ 3-4 months
Perinatal Brain injury
Disease / HistologyEarly: 20-25 week
- Schizencephaly / “Split brain”, Probably ischemic damage
- Porencephaly / Hole
- Hydrancephaly / No brain, but cranial vault IS present
Late: 25+ weeks
- Germinal matrix hemorrhage (preemies) / Parenchymal hemorrhage
- Choroid plexus hemorrhage (preemies) / Periventricular leukomalacia (PVL)
- White matter most sensitive in embryo (not gray neurons)
- Down’s syndrome / Small brain, short AP diameter, small temporal gyrus, ↓ dendrite complexity
Leukodystophies
Lysosome / Metachromatic
Arylsulfatase A deficiency / Autosomal recessive
Myelin breakdown stains red
Krabbe’s (Globoid)
β-galactocerebrosidase def / Periventricular ‘pages w/ myelin breakdown
β-galactocerebroside buildup
Peroxisome / Adrenoleukodostryphy / X-linked. Late-onset, see in school age
Can’t metab long-chain FAs (only in brain)
Demyelinating Diseases
- Multiple sclerosis
o Lesions separated in space and time
o Significant genetic component
o Doesn’t “respect anatomy boundaries”
o 20-40 years old. Progressive
o Can be triggered by infection
o Type IV + II hypersensitivity
o Autonomic dysfunction: can’t pee
o Bilateral Internuclear Opthalmoplegia
§ Characteristic. MLF demyelination
- Acute disseminated encephalomyelitis (ADEM)
o Perivascular: follow infection or immunization
o NOT progressive: die or 100% resolve
- Acute Necrotizing Hemorrhagic Encephalitis
o Hyperacute variant
- Central Pontine Myelinosis (often alcoholics)
o Iatrogenic: too rapid hyponatremia overcorrection
o Rapid quadriplegia
- Progressive Multifocal Leukoencephalopathy
o JC virus infection of oligodendrocytes
- Subacute sclerosing Panencephalitis
o Measles Dawson’s bodie / Infections
Disease / Histology
Viral / - Perivascular lyphocytic cuffing
- Microglial Rod cells + nodules
- Neurophagia
Herpes simplex / - Cowdry type A in nucleus
Rabies (NCAM recep) / - Negri bodies in cytoplasm of perkinje cells etc)
CMV / - Periventricular calcification
- “Owl eye” nucleus ↑ Cytoplasm
HIV (not neurons!)
- CMV, Toxo, Cryptococcus, PML(bizarre astroc) / - Infections microglia +’phages
o ↑ Cytokines: encephalitis à AIDS dementia
- Vacuolar myelopathy of muscle (like B12 def)
- AIDS myopathy of muscle
Kuru / - “Spiked ball”
GSS / - Multicenteric
vCJD / - Florid **Lymphoid tissue**: tonsils
Cerebrovascular Diseases
Disease / HistologyGlobal Ischemia: Global ischemic encephalopathy / - Pseudolaminar necrosis
Focal Iscemia: Infarction (80% strokes)
- Thrombus
- Embolism
- Cerebral amyloid angiopathy (Amyloid β)
- Vasculitis: Infection, autoimmune
- Hereditary angiopathy: CADSIL
o Cerebral Autosomal Dominant Arteriopathy with Subcortical infarcts and Leukoencephalopathy / 1. Acute (1 week): Blurred border
2. Subacute (2-3 weeks): Sharp border of liquefactive nec
3. Chronic (4+ weeks): Cavitation, gliosis
Intracerebral hemorrhage (10% strokes)
- Hypertension / Basal gangia, pontine, cerebellar
o Berry aneurysms
§ Death: 25-50%, Acute vasospasm, Chronic meningial fibrosis (hydrocephalus), re-bleeding common / Subarachnoid hemorrhage
- Vascular malformations
o AV malformation (most likely to bleed) / - Seizures
o Cavernous hemangioma / - No brain tissue in between veins
o Venous malformation / - Brain tissue in between veins (hemorrhage doesn’t occur)
o Vapillary telangiectasias (rare) / - Incidental finding at autopsy
Hypertension
Disease / HistologyAcute Hypertension / - Fibrinoid Necrosis
Chronic / - Hyalinization à Lacunes
- Charcot-Bouchard aneurysms
- Arteries / - Atherosclerosis
- Arterioles / - Arteriolosclerosis
- Widened perivascualr spaces
- Vascular dementia: Multiple small infarcts (stepwise)
- White patter infarcts (Binswanger Disease): Pale white matter
o DDx: Leukoaraiosis
§ Normal periventricular signal changes in elderly
Degenerative Diseases
D / FTD w/Parkinsons / - Chromosome 17 mutation (No Aβ)
Pick Disease / - Knife edge giri - Pick bodies: (Round, not in axon)
D / P / Progressive Supranuclear palsy / - *Eye problems* - Neuronal AND glial *Brainstem
P / Corticobasal Degeneration / - *Neurons AND glia* Atrophy of motor cortex, ballooned neurons
U / D / Motor Neuron Disease w/Dementia / - Ubiquitin-positive inclusions in neurons
α- synuclein / P / Parkinson’s Disease / - Lewy bodies, α- synuclein
D / P / Dementia w/Lewy Bodies
Multiple System atrophy / - α- synuclein in Oligodendrocytes
- Striatonigran degeneration: Parkinsonism
- Olivopontocerebellar atrophy: Cereballar ataxia
- Shy-Drager: ANS dysfunction