Central nervous system
review

• Meningitis – inflammation of pia + arachnoid (leptomeninges)

• Acute aseptic (viral)
  • Most common: enterovirus
  • Lymphocytic infiltrate, superficial cortex
  • Fever, meningeal signs, depressed consciousness
  • Good prognosis; self‑limited

• Acute purulent (bacterial)
  • S. pneumoniae – infants, children, adults
  • Neonates: group B strep (most fatal: E. coli)
  • N. meningitidis – teens/young adults, maculopapular rash
  • Listeria – age >50, cell‑mediated immunity defects
  • Opaque leptomeninges, neutrophilic infiltrate, cerebral edema → herniation risk
  • Classic triad: fever, nuchal rigidity, altered mental status

• Mycobacterial / fungal
  • M. tuberculosis / atypical: basal meningeal enhancement, hydrocephalus
  • Fungal: Aspergillus, Mucor – vascular tropism → vasculitis, hemorrhage
  • Cryptococcus – diffuse meningoencephalitis, soap‑bubble lesions

• Encephalitis – brain parenchyma inflammation
  • Perivascular cuffs, microglial nodules, neuronophagia
  • Arthropod‑borne: St. Louis, Eastern/Western equine
  • HSV‑1: hemorrhagic necrosis of temporal lobes, Cowdry type A inclusions
  • Rabies: Negri bodies (hippocampus, Purkinje)
  • HIV: microglial nodules, multinucleated giant cells; vacuolar myelopathy

• Progressive multifocal leukoencephalopathy (PML)
  • JC polyomavirus; immunocompromised
  • Demyelination, enlarged oligodendrocytes; high mortality

• Subacute sclerosing panencephalitis
  • Measles (age <2), 6‑15y later: progressive dementia, seizures
  • Fatal within 1‑2 years

• Cerebral abscess
  • Hematogenous or direct spread (mastoiditis, sinusitis, open fracture)
  • Ring‑enhancing lesion; ↑ICP (headache, vomiting, papilledema)
  • Toxoplasmosis (AIDS): central necrosis, chronic inflammation

• Prion (CJD)
  • PrP^sc (β‑pleated) converts normal PrP^c (α‑helix)
  • Spongiform change, neuronal loss, astrogliosis
  • 85% sporadic; rapidly progressive dementia + startle myoclonus; death 6‑12 mo
  • Variant CJD: younger, bovine spongiform encephalopathy exposure

• Global cerebral ischemia – shock, cardiac arrest → watershed infarcts, cortical laminar necrosis; vulnerable: hippocampus (CA1), Purkinje, pyramidal neurons

• TIA – reversible <24h; platelet thrombi / atheroemboli

• Infarction (85% of strokes)
  • Thrombotic: anemic (white) infarct, atherosclerosis
  • Embolic: hemorrhagic infarct; cardiac source
  • Lacunar: small‑vessel disease, hypertension → hyaline arteriolosclerosis

• Hemorrhage (15% strokes)
  • Intracerebral: hypertension (basal ganglia, cerebellum, pons); vascular malformations, amyloid angiopathy
  • Subarachnoid: berry aneurysm (circle of Willis) → sudden “worst headache”, nuchal rigidity
  • Berry aneurysm: intima + adventitia only; rupture → ⅓ die, ⅓ recover, ⅓ rebleed; associated with ADPKD, Marfan, EDS type 4

• Concussion – transient loss of function, amnesia; pathogenesis uncertain

• Contusion – bruising; orbital gyri, frontal/temporal poles; coup + contrecoup
  • Acute: wedge‑shaped hemorrhage
  • Subacute: necrosis, liquefaction
  • Remote: “plaque jaune” (yellow depressed cortex)

• Epidural hematoma – middle meningeal artery; lucid interval

• Subdural hematoma – bridging veins; elderly, brain atrophy; recurrent

• Diffuse axonal injury – shearing at nodes of Ranvier; coma without parenchymal lesion; corpus callosum, periventricular, peduncles

• Spinal cord injury – thoracic → paraplegia; cervical → tetraplegia; above C4 → respiratory arrest

• Chronic traumatic encephalopathy – neurofibrillary tangles, cerebellar atrophy, substantia nigra hypopigmentation

• Herniation syndromes
  • Subfalcine: cingulate under falx → ACA compression
  • Transtentorial (uncal): CN III compression → ipsilateral pupillary dilatation; Duret hemorrhages in pons/midbrain
  • Tonsillar: through foramen magnum → medulla compression → cardiorespiratory arrest

• Neural tube defects – folate deficiency; anencephaly (incompatible), spina bifida variants
  • Spina bifida occulta: bony defect
  • Meningocele: meningeal outpouching
  • Meningomyelocele: meninges + cord + roots
  • Myelocele: exposed cord

• Syringomyelia – ependymal‑lined cyst; 90% with Arnold‑Chiari type 1; progressive cord destruction

• Perinatal injury – germinal matrix hemorrhage (premature); periventricular leukomalacia; multicystic encephalopathy

• Fetal alcohol syndrome – microcephaly, corpus callosum agenesis, cerebellar hypoplasia

• Cerebellar malformations
  • Dandy‑Walker: 4th ventricle dilation, vermis hypoplasia
  • Arnold‑Chiari type 1: tonsillar descent (often asymptomatic, syringomyelia)
  • Type 2: small posterior fossa, hydrocephalus, lumbar meningomyelocele

• Multiple sclerosis – autoimmune, relapsing‑remitting; plaques (periventricular, optic nerves, spinal cord)
  • Prevalence 1/1000; women 2×; HLA‑DR15
  • Acute: inflammation, myelin phagocytosis (axons preserved)
  • Chronic: thinner myelin, slower conduction
  • Relapsing‑remitting (85%); early: sensory, paresis, visual; later: bladder, spasticity, ataxia
  • Dx: dissemination in space/time; MRI, CSF, evoked potentials
  • Tx: interferon β, mitoxantrone, natalizumab (risk PML)

• Central pontine myelinolysis – rapid correction of hyponatremia; malnourished / alcoholics; often fatal

• Parkinson disease – substantia nigra dopamine loss; Lewy bodies (α‑synuclein); tremor, rigidity, bradykinesia; smoking/caffeine protective; treatment: carbidopa/levodopa, DBS

• Huntington disease – autosomal dominant; CAG repeat (HTT); caudate GABAergic loss → chorea, cognitive decline; anticipation

• Alzheimer disease – 60% dementia; Aβ plaques, neurofibrillary tangles (hyperphosphorylated tau); hippocampus, temporal lobe; APOE ε4 risk; early‑onset genes: APP, PSEN1, PSEN2; Tx: acetylcholinesterase inhibitors (mild)

• Lewy body dementia – neocortical Lewy bodies; visual hallucinations, parkinsonism, cognitive decline

• ALS – upper + lower motor neuron; hyperreflexia/spasticity + weakness/fasciculations; SOD1 mutations (5‑10%); respiratory failure

• Friedreich ataxia – autosomal recessive; GAA expansion (frataxin); mitochondrial iron; sensory ataxia, loss of reflexes, diabetes, cardiomyopathy

• Wilson disease – (see liver) copper accumulation

• Acute intermittent porphyria – uroporphyrinogen synthase deficiency; PBG, ALA ↑; dark urine; abdominal pain, psychosis, neuropathy

• Vitamin B12 deficiency – subacute combined degeneration (posterior columns + corticospinal), dementia, peripheral neuropathy

• Alcohol / thiamine deficiency – Wernicke (confusion, ataxia, nystagmus) → Korsakoff (irreversible amnesia); mamillary body hemorrhages; central pontine myelinolysis

• General – 20% pediatric tumors (posterior fossa); adults supratentorial; WHO grade I‑IV; metastasis rare

• Astrocytoma – GFAP+; pilocytic (children, cystic, BRAF, Rosenthal fibers); diffuse (IDH1+); anaplastic; glioblastoma (necrosis, vascular proliferation, butterfly glioma) – median survival 15 mo

• Oligodendroglioma – cortical, seizures; perinuclear halos (artifact); 1p/19q co‑deletion → better response

• Ependymoma – 4th ventricle (children), pseudorosettes; spinal in adults; NF2 association

• Medulloblastoma – embryonal, most common malignant pediatric; Wnt subgroup best prognosis

• Schwannoma – CN8 (CPA), unilateral hearing loss; Antoni A/B, Verocay bodies, S‑100+; bilateral = NF2

• Meningioma – arachnoid cells; women > men; whorls, psammoma bodies; chromosome 22; NF2

• Craniopharyngioma – suprasellar, children; calcifications, adamantinomatous; β‑catenin mutations

• Lymphoma – immunocompromised, multiple; poor chemo response

• Germ cell tumors – children, germinoma (seminoma‑like); radiosensitive

• Metastatic – 25‑50% of CNS tumors; carcinomas; grey‑white junction