13.3 Disorders of the Nervous System

Why nervous-system pathology is a scored Pathology topic

Quick Answer: Red neurons at 12–24 hours mark ischemic injury. Put the blood in the right extra-axial space. Putamen is hypertensive; ACom is berry. MS is CNS myelin; GBS is PNS myelin. Match the inclusion (Aβ/tau, α-synuclein, polyglutamine huntingtin) to the nucleus that atrophies. Uncal herniation blows the ipsilateral pupil.

Stroke: ischemia and hemorrhage

Global ischemia (cardiac arrest, severe hypotension) hits the watershed cortices (ACA–MCA zone), CA1 hippocampus, and cerebellar Purkinje cells. Survivors may show laminar cortical necrosis. Focal ischemia is arterial territory disease.

Infarct histology clock: 12–24 h red neurons (eosinophilic cytoplasm, pyknotic nuclei); 24–72 h neutrophils; 3–5 days macrophages (gitter cells); 1–2 weeks reactive astrocytes; months later a cystic cavity lined by gliosis. Brain infarcts are liquefactive, not coagulative—the exception you already learned in fundamentals.

Hypertensive intracerebral hemorrhage ruptures Charcot-Bouchard microaneurysms of small penetrating arteries. Ranked sites: putamen (most common), thalamus, pons, cerebellum. The hematoma is deep, not lobar. Cerebral amyloid angiopathy (Aβ in small cortical vessels of the elderly, often with Alzheimer disease) causes lobar hemorrhages. Saccular (berry) aneurysms form at branch points of the circle of Willis—anterior communicating artery most often, then posterior communicating (acute CN III palsy) and MCA bifurcation. Associations: ADPKD, Ehlers-Danlos type IV, coarctation, smoking, hypertension. Rupture is subarachnoid hemorrhage: thunderclap headache, nuchal rigidity, xanthochromia. Traumatic SAH also exists; the berry story is the nontraumatic exam default.

Trauma and raised intracranial pressure

Raised ICP produces headache, vomiting, papilledema, and Cushing’s triad (hypertension, bradycardia, irregular respiration). Herniation syndromes are geography:

• Subfalcine: cingulate gyrus under falx → ACA compression → contralateral lower-limb weakness.
• Uncal (transtentorial): medial temporal lobe → CN III (ipsilateral blown pupil, down-and-out eye) and PCA (occipital infarct, contralateral hemianopia). The ipsilateral cerebral peduncle is compressed (contralateral hemiparesis). Kernohan notch: the opposite peduncle is crushed against the tentorium, producing ipsilateral hemiparesis (false localizing).
• Tonsillar: cerebellar tonsils through foramen magnum → medullary compression, respiratory arrest.
• Central downward: progressive midbrain then pontine Duret hemorrhages.

An expanding epidural after a lucid interval is the classic uncal-herniation race. That is mechanism, not a surgical protocol.

Infection

Acute bacterial meningitis is a neutrophilic exudate in the leptomeninges; CSF is high protein, low glucose, high WBC with PMNs. Age-organism pairs: neonate (GBS, E. coli, Listeria); child (N. meningitidis, remaining unvaccinated H. influenzae); adult (S. pneumoniae); elderly and neonate again Listeria. Meningococcus adds purpura and Waterhouse-Friderichsen adrenal hemorrhage. Brain abscess is a ring-enhancing liquefactive cavity with a fibrotic wall (from S. aureus, strep, anaerobes, or right-to-left shunt).

Viral (aseptic) meningitis is lymphocytic, normal glucose. HSV-1 encephalitis is hemorrhagic necrosis of medial temporal and inferior frontal lobes (Cowdry A inclusions). HIV produces microglial nodules and multinucleated giant cells. JC virus causes progressive multifocal leukoencephalopathy: oligodendrocyte infection, demyelination, bizarre astrocytes, almost no inflammation, in AIDS or natalizumab-treated MS. Toxoplasma in AIDS is multiple ring-enhancing basal-ganglia lesions (versus primary CNS lymphoma, often solitary and EBV-related). Cryptococcus is soap-bubble perivascular spaces and a positive India-ink/cryptococcal antigen CSF. Prion disease (CJD) is spongiform change, neuronal loss, and protease-resistant PrP—no inflammation, startle myoclonus, rapidly progressive dementia.

Tabes dorsalis (tertiary syphilis) demyelinates dorsal roots and columns (proprioceptive loss, Argyll Robertson pupils). Polio (and West Nile) kills anterior-horn LMNs.

Demyelination and degeneration

Multiple sclerosis is the prototype CNS demyelinating disease: autoimmune attack on oligodendrocyte myelin, relatively preserved axons early, perivascular lymphocytes. Plaques favor periventricular white matter (Dawson fingers perpendicular to the ventricle), optic nerves, brainstem (MLF → internuclear ophthalmoplegia), and cervical cord. CSF shows oligoclonal IgG bands. Relapsing-remitting young women are the demographic default; HLA-DR2 is the haplotype often cited. Charcot’s triad (scanning speech, nystagmus, intention tremor) is cerebellar. Neuromyelitis optica is aquaporin-4 astrocytopathy: longitudinally extensive cord plus optic nerves, not garden-variety MS.

Guillain-Barré syndrome (AIDP) is the prototype PNS demyelinating disease: endoneurial inflammation and macrophage stripping of Schwann myelin, often 1–3 weeks after Campylobacter (molecular mimicry with gangliosides), also CMV, EBV, or vaccination in rare stems. Ascending areflexic paralysis, autonomic instability, and respiratory failure are the risks. CSF shows albuminocytologic dissociation (high protein, normal WBC). Miller Fisher variant (ophthalmoplegia, ataxia, areflexia) associates with anti-GQ1b. Contrast: MS is central and oligoclonal; GBS is peripheral and protein-high.

Parkinsonism after MPTP or after hydrocephalus is not Lewy-body disease. Multiple-system atrophy and progressive supranuclear palsy are tau or α-synuclein cousins with extraocular or cerebellar extras—know they exist; the four rows in the table carry most Part I points.

CNS tumors

Adults: most common primary malignant is glioblastoma; most common CNS mass overall is metastasis (gray–white junction, lung/breast/melanoma/kidney/GI). Children: posterior fossa dominates.

Peripheral neuropathies and compression

Axonal neuropathies (diabetes, toxins, vasculitis) reduce amplitude; dying-back starts distally (stocking-glove). Demyelinating neuropathies (GBS, CIDP, CMT1) slow conduction velocity and can show onion bulbs when chronic. Wallerian degeneration is the distal axon and myelin collapsing after a cut; the soma undergoes chromatolysis.

Charcot-Marie-Tooth type 1A is usually PMP22 duplication: demyelinating, AD, inverted-champagne-bottle legs, foot drop. Diabetic neuropathy is the most common acquired pattern: distal symmetric sensory (sorbitol via aldose reductase, microvascular ischemia), small-fiber pain, and autonomic (gastroparesis, orthostasis, impotence). Mononeuritis multiplex suggests vasculitis (polyarteritis, diabetes).

Compression (entrapment) sites that overlap spinal anatomy:

GBS is inflammatory demyelination of many roots at once, not a single entrapment. A single night of compression does not produce albuminocytologic dissociation. Keep MS out of the peripheral-nerve answers: oligodendrocytes are CNS, Schwann cells are PNS.