Neuro Flashcards
Acute Neuronal Injury
- changes secondary to hypoxia/**ischemia **⇒ cell necrosis or apoptosis.
- intense cytoplasmic eosinophilia and nuclear pyknosis = red neurons
Subacute and Chronic Neuronal Injury
- degeneration = neuronal death and reactive gliosis
- trans-synpatic degeneration when afferent inputs to neuron are lost.
Axonal Reaction
- response of neuronal cell body to challenge of regenerating damaged axons.
- cell body rounds up and nucleoli enlarge.
- Nissl substance dispersal and perinuclear cytoplasmic pallor (central chromatolysis) = ↑ protein synthesis and axonal sprouting
Neuronal Inclusions
- manifestation of aging (lipofuscin), disorders of metabolism (storage material), viral diseases (inclusion bodies), or neurodegenerative diseases with aggregated proteins.
Astrocytes
- principal cells for repair and scar formation in brain.
- important for blood brain barrier.
- with CNS damage, get enlarged vesicular nuclei and conspicuous eosinophilic cytoplasm (gemistocytic astrocytes)
- astrocyte hypertrophy and hyperplasia ⇒ gliosis
-
directly injured ⇒ rosenthal fibers, corpora amylacea, alzheimer type II astrocytes.
- rosenthal fibers = elongated, eosinophilic structure in astrocyte processes containing alphaB-crystallin and hsp27. see in long-standing gliosis or pilocytic astrocytomas.
- corpora amylacea = lamellated polyglucosan bodies and hsp. ↑ with age, are degenerative change.
- Alzheimer type II astrocytes = enlarged nucleus with intranuclear glycogen and pale chromatin. occurs with hyperammonemia.
Glial Cell Injury
- oligodendroglial cell apoptosis feature of demyelinating disorders and leukodystrophies.
- viral inclusions in progressive multifocal leukoencephalopathy
- alpha-synuclein inclusions in multiple system atrophy (MSA)
- ependymal cells don’t regenerate. damage ⇒ proliferation of subependymal astrocytes = ependymal granulations
Cerebral Edema
-
vasogenic = ↑ vascular permeability ⇒ accumulate intercellular fluid.
- focal or generalized.
- absence of lymphocytes impairs resorption.
- cytotoxic = ↑ intracellular fluid 2° to endothelial, neuronal, or glial injury.
- interstitial = fluid from ventricular system transudates across ependyal lining from ↑ intraventricular pressure.
Hydrocephalus
- obstruction of CSF flow ⇒ ventricular enlargement and ↑ CSF volume
- from impaired flow or resorption, overproduction uncommon.
- occurs prior to cranial suture closure ⇒ enlarged head.
- occurs after cranial suture closure ⇒ ventricular expansion and ↑ ICP
- non-communicating = enlargement of a portion of the ventricle system.
- communicating = entire system expanded
- hydrocephalus ex vacuo = extensive tissue loss ⇒ compensatory expansion of entire CSF compartment
Subfalcine Herniation
- aka cingulate herniation.
- from ↑ ICP.
- can compromise branches of anterior cerebral artery.
Transtentorial Herniation
- aka uncinate, mesial temporal herniation.
- distorts adjacent midbrain and pons.
- 3rd CN compromise ⇒ pupillary dilation
- compression of posterior cerebral artery ⇒ ipsilateral hemiparesis
- Duret hemorrhages = tearing of feeding vesels.
Tonsillar Herniation
- through foramen magnun ⇒ compress medulla and compromise cardiac and respiratory centers.
Neural Tube Defects
- primary failure to close or secondary reopening.
- abnormalities in some combo of neural tissue, meninges, and ovelrying bone and soft tissues.
- risk factors: folate deficiency.
- antenatal diagnosis through alpha-fetoprotein screening.
- encephalocele, anencephaly, spina bifida, myelomeningocele.
Encephalocele
- malformed CNS diverticulum extending through defect in cranium (occiput or posterior fossa)
Anencephaly
- malformation of anterior neural tube ⇒ failure of cerebrum development
Spina Bifida
- occulta = asymptomatic bony defect
- or a severe malformation with flattened, disorganized cord segment with overlying meningeal outpouching.
Myelomeningocele
- CNS outpouching through vertebral column defect.
- mostly lumbrosacral region with lower extremity motor and sensory deficits and disturbed bowel and bladder control.
Forebrain Anomalies
- issues with brain size: microencephaly, lissencephaly, agyria, megalencephaly.
- issues with gyral formation and organization: polymicrogyria, neuronal heterotopias, holoprosencephaly, agenesis of corpus callosum.
Microencephaly
- small brain.
- too many periventricular cells proliferate too soon.
- from chromosomal abnormalities, fetal alcohol syndrome, in uter HIV.
Lissencephaly
- aka agyria.
- smooth brain, few to no gyri.
- too many periventricular cells proliferate too soon.
- from chromosomal abnormalities, fetal alcohol syndrome, in utero HIV.
Megalencephaly
- large brain.
- too few periventricular cells proliferate at early stages ⇒ overproduction of neurons.
Polymicrogyria
- small, overabundant cerebral convolutions from focal injury near end of neuronal migration.
Neuronal Heterotopias
- abnormal clusters of neurons in inappropriate locations along normal migratory routes.
- associated with epilepsy.
- mutations in filamin A or microtubule associated proteins.
Holoprosencephaly
- incomplete separation of cerebral hemispheres.
- midline facial abnormalities (cyclopia).
- mutation of sonic hedgehog or other genes in neural development.
Agenesis of Corpus Callosum
- normal white matter interhemispheric bundles not formed.
- may have mental retardation but clinically most are normal.
Posterior Fossa Anomalies
- Dandy-Walker Malformation
- **Arnold-Chiari Malformation **
- Chiari I malformation
Dandy-Walker Malformation
- enlarged posterior fossa, absent cerebellar vermis, large midline cyst with brainstem nuclei dysplasias.
Arnold-Chiari Malformation
- aka Chiari II malformation
- small posterior fossa, malformed midline cerebellum, extension of vermis through foramen magnum, hydrocephalus, lumbar myelomeningocele.
Chiari I Malformation
- low-lying cerebellar tonsils extend into vertebral canal.
- clinically silent but can present with CSF flow obstruction.
Syringomyelia
- formation of cleftlike cavity in spinal cord.
- morphology: gray and white matter destruction surrounded by reactive gliosis.
- presentation: loss of pain and temperature sensation in upper extremities.
Hydromyelia
- expansion of central canal.
- morphology: gray and white matter destruction surroudned by reactive gliosis.
- presentation: loss of pain and temperature sensation in upper extremities.
Perinatal Brain Injury
- non-aggressive motor deficits from pre- and perinatal neurologic insults.
- risk factor: prematurity.
- can have brain injury without reactive gliosis.
- intraparenchymal hemorrhage, periventricular leukomalacia, multicystic encephalopathy, ulegyria, status marmoratus.
- presentation: depends on location but includes dystonia, spasticity, ataxia/athetosis, and/or paresis
Perinatal Intraparenchymal Hemorrhage
- in germinal matrix btw thalamus and caudate nucleus. can extend to ventricular system.
Periventricular Leukomalacia
- ischemic infarcts in periventricular white matter.
Multicystic Encephalopathy
- ischemic infarcts within the hemispheres.
Ulegyria
- thin, gliotic gyri from perinatal cortical ischemia.
Status Marmoratus
- ischemic neuronal loss and gliosis in basal ganglia and thalamus with aberrant and irregular myelin formation.
Skull Fractures
- fracture resistance varies with skull bone thickness.
- displaced fracture = bone shifts into cranial vault by more than its thickness.
- accidental falls = occiput. 2° basal skull involved with lower CN or cervicomedullary symptoms, CSF discharge, and/or meningitis.
- syncope ⇒ frontal skull.
- diastatic fractures = transverse sutures.
Concussion
- transient trauma-related clinical syndrome with loss of consciousness, temporary respiratory arrest, loss of reflexes, amnesia of event.
Direct Parenchymal Injury (Brain)
- lacerations = penetrating injury causes tissue tearing.
-
contusions = CNS bruises.
- gyral crest very susceptible.
- coup contusion = at site of impact
- contrecoup = on opposite side of cranium from impact
- brain hemorrhage and edema resolves ⇒ depressed, yellow-brown glial scar going to pial surface = plaque jaune
Diffuse Axonal Injury
- when mechanical forces (acceleration) disrupt axonal integrity and axoplasmic flow.
- widespread axonal swelling and focal hemorrhage ⇒ degenerated fibers and gliosis.
- 1/2 pts comatose after trauma have diffuse axonal injury even without contusions.
Epidural Hematoma
- rupture of **dural arteries (middle meningeal artery) **⇒ blood btw dura and skull ⇒ compress brain.
- can have lucid period several hours after trauma
Subdural Hemorrhage
- tearing of veins that stretch from cortical surface through subarachnoid and subdural spaces into draining veins (superior sagittal sinus).
- after traumatic shifting of brain.
- geriatric pts with cerebral atrophy susceptible.
- presentation: non-localizing headache, confusion within 48hrs of injury.
- chronic subdural hematoma = recurrent episodes of bleeding from hemorrhage of thin-walled vessels of granulation tissue.
- tx: surgical drainage and remove granulation tissue.
Sequelae of Brain Trauma
- epilepsy, meningiomas, infectious disease, psychiatric disorders.
- post-traumatic hydrocephalus = hemorrhage into subarachnoid space obstructs CSF resorption
- post-traumatic dementia = dementia pugilistica. repeated head trauma ⇒ hydrocephalus, corpus callosum thinning, diffuse axonal injury, amyloid plaques, and neurofibrillary tangles.
Spinal Cord Trauma
- displacement of spinal column.
- injury level:
- thoracic vertebrae or below ⇒ paraplegia.
-
cervical vertebrae ⇒ quadriplegia.
- C4 and above ⇒ respiratory compromise from diaphragm paralysis.
- acute = hemorrhage, necrosis, white matter axonal swellings
- later = cystic and gliotic. ascending and descending white matter tracts do 2° degeneration.
Global Cerebral Ischemia
- hypoxia from reduced blood flow or hypotension.
- neurons more sensitive to hypoxia.
-
severe ⇒ widespread neuronal cell death, pt vegetative state or brain dead.
- brain dead = flat EEG, absent reflexes/respiratory drive/cerebral perfusion
- kept on ventilator ⇒ brain autolyzes.
-
watershed/border zone infarcts = oxygenation incompletely compromised. interface between major vessels.
- btw anterior and middle cerebral arteries most vulnerable.
-
morphology: edematous with widened gyri and narrowed sulci. poor gray/white demarcation.
- red neurons 12-24hrs post injury. pyramidal neurons in hippocampus CA1 (Sommer sector), cerebellar Purkinje cells, cortical pyramidal neurons most susceptible.
- then neutrophil infiltration ⇒ macrophage influx, neovascularization, reactive gliosis.
- pseudolaminar necrosis = uneven cortical neuronal loss and gliosis alternating with preserved zones.
Stroke
- brain oxygen deprivation from global or focal ischemic necrosis.
- outcome depends on collateral circulation, duration of ischemia, magnitude and rapidity of flow reduction.
Focal Cerebral Ischemia
- infarction from obstruction of local blood supply ⇒ thrombotic or embolic arterial occlusion.
- thrombosis = from atherosclerosis. affects extracerebral carotid system and basilar artery.
- embolism = involves intracerebral arteries (middle cerebral). comes from atheromatous cerebrovascular plaques, cardiac mural trhombi, valvular lesions, or paradoxical embolisms.
- inflammatory lesions can ⇒ lumenal narrowing and cerebral infarct.
- venous infarcts after occlusion of superior sagittal sinus or deep cerebral veins. are hemorrhagic.
-
morphology: nonhemorrhagic infarcts = bland/anemic infarcts. see at 48hrs as pale, soft regions of edematous brain with neutrophils. then liquefies ⇒ fluid-filled cavity with macrophages lined by reactive glia.
- hemorrhagic infarcts = embolic occlusion with reperfusion injury, have blood extravasation.
Lacunar Infarcts
- small cystic infarcts from cerebral arteriolar sclerosis and occlusion.
- lipid-laden macrophages and surrounding gliosis.
- affects: lenticular nucleus, thalamus, internal capsule, deep white matter, caudate nucleus, and pons.
Slit Hemorrhages
- when HTN causes small vessel rupture.
- they resorb leaving hemosiderin-laden macrophages and gliosis.
Acute Hypertensive Encephalopathy
- ↑ ICP ⇒ diffuse cerebral dysfunction (headaches, confusion, vomiting, convulsions, coma).
- need rapid intervention.
- post mortem shows edematous brain with petechiae and arteriolar fibrinoid necrosis. somtimes see herniation.
Chronic Hypertensive Injury
-
recurrent small infarcts ⇒ vascular (multi-infarct) dementia
- dementia, gait abnormalities, pseudobulbar signs, focal neuro deficits.
- Binswanger disease = pattern of recurrent ischemic injury involves subcortical white matter with myelin and axonal loss.
Intracerebral Hemorrhage
- spontaneous rupture of small intraparenchymal vessel.
- age >60yrs.
- causes:
- HTN in 50%. ⇒ hyaline arteriosclerosis and vessel weakening, focal vessel necrosis, Charcot-Bouchard aneurysms. in putamen (50-60%), thalamus, pons, cerebellar hemispheres.
- cerebral amyloid angiopathy (CAA): 2nd most common. ** amyloidogenic peptides deposited in vessel walls** ⇒ weakening. lesions have stiff amyloid deposits in leptomeningeal and cerebral cortical vessels.
- cerebral autosomal dominanty arteriopathy with subcortical infarcts (CADASIL): mutation in Notch3 receptor. vessels have concentric medial and adventitial thickening with basophilic granular depostis and smooth muscle drop-out
Subarachnoid Hemorrhage
- usually from berry (saccular) aneurysm rupture, traumatic hematomas, vascular malformations, HTN intracerebral hemorrhage, tumors, hematologic disturbances.
-
pathogenesis: 90% berry aneurysms in anterior circulation near arterial branch points.
- can be with polycystic kidney disease (autosomal dominant), HTN, aortic coarctation, collagen disorders, neurofibromatosis type I, and fibromuscular dysplasia
- morphology: small with red shiny translucent wall. at aneurysm neck, the muscular wall and intimal elastic lamina are absent. sac wall is only thickened hyalinized intima.
-
presentation: rupture from ↑ ICP. excruciating headache, rapid loss of consciousness. re-bleeding common with worse episode each time the aneurysm bleeds.
- blood in subarachnoid ⇒ arterial vasospasm.
- blood resorption ⇒ meningeal fibrosis and hydrocephalus
Arteriovenous Malformation
-
tangles of abnormalled tortuous and misshapen vessels, shunting arterial blood into venous circulation.
- usually MCA.
- 2:1 m:f
- presentation: btw ages 10-30yrs as seizure disorder, intracerebral hemorrhage, or subarachnoid hemorrhage
Cavernous Hemangiomas
- distended, loosely organized vascular channels with thin, collagenized walls.
- usually cerebellum, pons, and subcortical regions.
- low flow without arteriovenous shunting.
Capillary Telangiectasias
- microscopic foci of dilated, thin-walled vascular channels separated by normal brain parenchyma.
- in pons.
Venous Angiomas
- aka varices
- aggregates of ecstatic veins.
Foix-Alajouanine Disease
- venous angiomatous malformation in lumbosacral region.
- slowly progressive ischemia and neuro symptoms.
Acute Bacterial Meningitis
- neonates = E. coli and group B strep
- infants & kids = S. pneumoniae
- adolescents & young adults = N. meningitidis
- elderly = S. pneumoniae and L. monocytogenes
-
morphology: meningeal vessels engorged, purulent exudate.
- neutrophils in subarachnoid space. may have cerebritis.
- phlebitis ⇒ venous thrombosis and hemorrhagic infarction.
- resolution ⇒ leptomeningeal fibrosis and hydrocephalus
-
presentation: fever, headache, photophobia, irritability, clouded sensorium, neck stiffness.
- CSF purulent with neutrophils and organisms, ↑ protein, and ↓ glucose.
Acute Viral Meningitis
- meningeal irritation, CSF lymphocytic pleocytosis, mod ↑ protein, normal glucose.
- self-limited.
Brain Abscess
- destructive lesion coming from bacterial endocarditis, congenital heart disease, chronic pulmonary sepsis, or immunosuppression.
- mainly strep and staph.
- morphology: central region of liquefactive necrosis. older have fibrous capsule with reactive gliosis and marked vasogenic edema.
-
presentation: progressive focal neurologic deficits and signs of ↑ ICP.
- subdural space infected ⇒ thrombophlebitis ⇒ venous occlusion and brain infarction.
Tuberculous Meningitis
- can ⇒ arachnoid fibrosis, hydrocephalus, obliterative endarteritis
-
morphology: diffuse meningoencephalitis. subarachnoid has gelatinous or fibrinous exudate of chronic inflammatory cells. granulomas at base of brain are rare ⇒ obliterate cisternae and encase cranial nerves.
- arteries in subarachnoid may have obliterative endarteritis.
-
presentation: headache, malaise, mental confusion, vomiting.
- mod CSF mononuclear cell pleocytosis, ↑ protein, mod ↓ or normal glucose.
Neurosyphilis
- tertiary stage of disease, 10%.
- ↑ risk in HIV pts.
- meningovascular neurosyphilis = chronic meningitis associated with obliterative endarteritis.
-
paretic neurosyphilis = from brian invasion by spirochetes with neuronal loss and microglial proliferation
- have insidious loss of mental and physical capacity with mood alterations ⇒ severe dementia.
- tabes dorsalis = from spirochete damage to dorsal root sensory neurons ⇒ impaired joint position sense, locomotor ataxia, loss of pain with secondary skin and joint damage (Charcot joints), absent deep tendon reflexes.
Neuroborreliosis
- in Lyme disease.
- includes septic meningitis, facial nerve palsies, encephalopathy.
- microglial proliferation and scattered organisms.
Arthropod-Borne Viral Encephalitis
- inflammed meninges or spinal cord.
- from Eastern and Wester Equine viruses, Venezuelan virus, St. Lous virus, La Crosse virus, West Nile virus.
- all have animal hosts and mosquito or tick vector.
- presentation: seizures, confusion, delirium, stupor or coma.
Hereps Simplex Virus Type I
- inflammed meninges or spinal cord.
- most common in kids or young adults.
-
morphology: hemorhagic, nectrotizing encephalitis of inferomedial temporal lobes and orbital gyri of frontal lobes.
- perivascular infiltrates with Cowdry A intranuclear viral inclusion bodies in neurons and glia.
-
presentation: alterations in affect, mood, memory, and behavior.
- protracted course = weakness, lethargy, ataxia, and seizures.
Herpes Simplex Virus Type II
- severe generalized encephalitis in 50% neonates born vaginally.
- ⇒ meningitis in adults, severe hemorrhagic, necrotizing encephalitis in HIV pts.
Varicella Zoster (Brain)
- shingles can cause persistent painful post-herpetic neuralgia syndrome.
- granulomatous arteritis, or necrotizing encephalitis in immunocompromised
Cytomegalovirus (Brain)
- in utero infection ⇒ periventricular necrosis, microcephaly, and periventricular calcification.
- in AIDS = opportunistic infection ⇒ subacute encephalitis with microglial nodules or periventricular hemorrhagic necrotizing encephalitis and choroid plexus.
- has classic CMV inclusions.
Poliomyelitis
- inflammation confined to anterior horns but can extend to posterior horns.
- meningial irritation and CSF picture of aseptic meningitis.
- involves lower motor neurons ⇒ flaccid paralysis with hyporeflexia and 2° muscle wasting.
- can get myocarditis, death from respiratory muscle paralysis.
- presentation: post-polio syndrome = 25-35yrs after polio, progressive weakness associated with pain and ↓ muscle mass.
Rabies (Brain)
- severe encephalitis from rabid animal or exposure to a bat without a bite.
- over 1-3 months the virus travels up peripheral nerves ⇒ CNS excitability, hydrophobia, flaccid paralysis.
- death from respiratory center failure.
- widespread neuronal necrosis and inflammation.
- worst in basal ganglia, midbrain, medulla.
- Negri bodies in hippocampal pyramidal cells and Purkinje cells.
HIV (Brain)
- 10% get aseptic meningitis within 1-2 wks of primary HIV infection.
- HIV encephalitis in symptomatic pts.
- only microglia express CD4 and chemokine receptors for efficient HIV infection.
- 80-90% get CNS lesions: direct viral pathogenic effects, opportunistic infections, and/or CNS lymphomas.
- HIV-associated dementia = related to extent of activated CNS microglia.
-
morphology: chronic inflammatory reaction with widely distributed microglial nodules, multinucleated giant cells, with necrosis and gliosis.
- most affects subcortical white matter, diencephalon, brain stem.
Progressive Multifocal Leukoencephalopathy
- from oligodendrocyte infection by JC polyomavirus in immunosuppressed pts.
- have evidence of prior JC exposure so is reexposure.
- develop progressive neuro manifestations from focal myelin destruction.
- morphology: demyelinated patches, greatly enlarged oligodendrocyte nuclei with viral inclusions. astrocytes with enlarged atypical nuclei.
Subacute Sclerosing Panencephalitis
- SSPE. progressive syndrome of cognitive decline, limb spasticity, and seizures.
- occurs months to years **after early age measles infection. **
- presistent but nonproductive CNS infection.
- widespread gliosis and myelin degeneration, associated with nuclear inclusions in oligodendrocytes and neurons.
- variable inflammation with neurofibrillary tangles.
Fungal Meningoencephalitis
- in immunocompromised patients with widespread hematogenous dissemination
- Candida, Mucor, Aspergillus, Cryptococcus.
- Histoplasma, Coccidioides, and Blastomyces involve CNS after pulmonary or cutaneous infections.
-
meningitis: by Cryptococcus.
- fulminant and fata within 2 wks or chronic and indolent over months-yrs.
-
vasculitis: Mucor and Aspergillus.
- vessel invasion with thrombosis and hemorrhagic infarction.
- granulomas or abscesses with Candida and Cryptococcus.
Toxoplasma gondii (Brain)
- seen in HIV pts.
- symptoms over 1-2 wks, are focal.
- multiple ring-enhanced lesions.
- abscesses with fre tachyzoites and encysted bradyzoites.
- maternal infection can ⇒ fetal cerebritis with multifocal necrotizing lesions that calcify.
Naegleria (Brain)
- causes rapidly fata necrotizing encephalitis.
Acanthamoeba
- associated with chronic granulomatous meningoencephalitis
Prion Diseases
- have spongiform changes (neuronal and glial intracellular vacuoles) caused by prion proteins. (PrP).
- infectious, sporadic, or familial.
- Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, and kuru.
-
pathogenesis: disease when becomes abnormally folded as beta-pleated sheet.
- can induce changes in normal PrP.
- polymorphisms at codon 129 (for methionine or valine) influence disease.
- heterozygosity at codon 129 is protective.
Creutzfeldt-Jakob Disease
- 85% sporadic. peaks btw 60-70yrs.
- presentation: subtle memory and behavior changes, then rapidly progressive dementia, with involuntary jerking muscle contractions.
- fatal. die ~7months after symptom onset.
Variant Creutzfeldt-Jakob Disease
- in young adults.
- early behavior manifestations and slower neurologic progression.
- linked to bovine spongiform encephalopathy.
- extensive cortical plaques with surrounding halo of spongiform change.
Gerstmann-Strauss-Scheinker Syndrome
- inherited disease with PRNP mutations.
-
morphology: spongiform transformation of cerebral cortex and deep gray matter structures (caudate and putamen).
- advanced = severe neuronal loss, reactive gliosis, expansion of vacuolated areas into cystlike spaces (status spongiosus).
- kuru plaques = extracellular aggregates of PrPsc proteins on congo-red and PAS-pos.
-
presentation: chronic cerebellar ataxia, then progressive dementia.
- death a few years after symptom onset.
Fatal Familial Insomnia
-
PRNP mutations substitute aspartate for asparagine at 178 of PrPc.
- mutation and methionine at 129 ⇒ FFI.
- valine at 129 ⇒ CJD.
- morphology: NO spongiform changes. ** neuronal loss and reactive gliosis in inferior olivary nuclei and anterior ventral and dorsomedial nuclei of thalamus**.
- presentation: sleep disturbances in initial stages.
Multiple Sclerosis
- autoimmune demyelinating disorder with distinct episodes of neurologic deficit separated in time and attributable to white matter lesions that are separated in space.
- F>M. peak age btw childhood and 50yrs.
-
relapsing and remitting with acute deficit onset and slow partial remission.
- relapse frequency increases over time but have steady neuro deterioration.
-
pathogenesis: cellular immune response against myelin.
- susceptibility linked to DR2 locus of major histocompatibility complex and polymorphisms in IL-2 and IL-4 receptor genes.
- initiated by TH1 and TH17 cells ⇒ myelin destruction.
- TH1 ⇒IFNgamma ⇒ activate macrophages
- TH17 ⇒ recruit leukocytes.
- CSF has oligoclonal Ig response = B cell response.
-
morphology: plaques are sharply defined areas of gray discoloration of white matter around ventricles.
-
active plaques have myelin breakdown, lipid-laden macrophages, and relative axonal preservation.
- lymphocytes and mononuclear cells at plaque edges and venules.
- inactive plaques lack inflammatory infiltrate, show gliosis.
- axons remain but are unmyelinated.
-
active plaques have myelin breakdown, lipid-laden macrophages, and relative axonal preservation.
-
presentation: unilateral vision impairment from optic neuritis.
- cranial nerve signs, ataxia, nystagmus, internuclear ophthalmoplegia from brainstem involvement.
- limb and trunk motor and sensory impairment, spasticity, and bladder dysfunction from spinal cord lesions.
Neuromyelitis Optica
- aka Devic disease.
- bilateral optic neuritis and spinal cord demyelinating lesions.
- white matter lesions = necrosis with acute inflammation, vascular Ig and complement deposits.
- Ab to aquaporins - important for astrocyte foot processes and BBB.
Acute Disseminated Encephalomyelitis
- diffuse demyelinating disese after viral infection.
- perivenular demyelination with axonal preservation, early neutrophil infiltrates then mononuclear cell inflammation and lipid-laden macrophages.
- presentation: headache, lethargy, and coma. no focal deficits. 20% die.
Acute Necrotizing Hemorrhagic Encephalomyelitis
- fulminant, commonly fatal, demyelinating syndrome in kids and young adults after upper respiratory tract infection.
- small vessel destruction and disseminated CNS necrosis.
- have perivascular demyelination with axonal preservation. early neutrophils then mononuclar cells then lipid-laden macrophages.
Central Pontine Myelinosis
- myelin damage with axonal preservation but without inflammation in basis pontis and portions of pontine tegmentum ⇒ spastic paresis.
- associated with rapid correction of hypnatremic state.
Alzheimer Disease
- begins after age 50yr. progressive insidious impairment of higher intellectual function over 5-10yrs.
- mostly sporadic.
- common cause of death = intercurrent disease (pneumonia)
-
morphology: cortical atrophy with narrowed gyri and widelned sulci in frontal, temporal, and parietal lobes. ** hydrocephalus ex vacuo**, medial temporal structures involved early.
- neuritic plaques and neurofibrillary tangles.
- cerebral amyloid angiopathy (CAA) = alpha-beta amyloid deposition
- granulovacuolar degeneration = formation of small clear intraneuronal cytoplasmic vacuoles.
- Hirano bodies = elongated, glassy eosinophilic paracrystalline arrays of beaded filaments, mostly actin.
-
pathogenesis: AB deposition can be neurotoxic ⇒ synaptic dysfunction, inflammation
- familial forms = mutation in APP on chromosome 21
- Down syndrome have early onset.
- early onset from **mutations in presenilin (PS1 or PS2) **⇒ enhanced gamma-secretase activity.
- apolipoprotein epsilon4 ⇒ ↑ risk
- familial forms = mutation in APP on chromosome 21
Frontotemporal Dementia with Parkinsonism Linked to Tau Mutations
- have parkinsonian symptoms
- mutation in MAPT (tau) gene, affects tau in microtubules.
-
morphology: frontal and temporal lobe atrophy.
- neuronal loss, gliosis, tau-containing neurofibrillary tangles.
- can have nigral degeneration or glial cell inclusions.
Pick Disease
- causes dementia.
- prominent frontal signs.
-
morphology: frontal and temporal lobe atrophy. spares posterior 2/3 of superior temporal gyrus. caudate and putamen can atrophy.
- large ballooned neurons (Pick cells) and smooth agyrophilic inclusions made of straight and paired helical filaments (Pick bodies)