12.4 Nervous System Pathology: Cerebrovascular Disease, Edema & Herniation, Infections, Degenerative & Demyelinating Disease, Tumors

Why this area matters

The TOS lists:

• cerebrovascular diseases;
• cerebral edema, hydrocephalus, increased intracranial pressure and herniation;
• infections;
• vascular diseases;
• degenerative and demyelinating diseases;
• tumors.

Stroke is one of the leading causes of death in the Philippines. CNS tuberculosis, bacterial meningitis, rabies and neurocysticercosis remain important infections.

Cerebrovascular disease

Ischemic stroke (about 80% of strokes):

• Thrombotic: atherosclerosis at the carotid bifurcation, middle cerebral artery and basilar artery.
• Embolic: from atrial fibrillation, mural thrombi or carotid plaques. These often affect the middle cerebral artery and may become hemorrhagic.
• Lacunar infarcts (under 15 mm): from hyaline arteriolosclerosis of penetrating arteries in hypertension and diabetes (basal ganglia, internal capsule, pons).
• Global hypoxic-ischemic injury: affects the most vulnerable neurons (hippocampal CA1, Purkinje cells, cortical layers 3 and 5) and causes watershed (border-zone) infarcts.

The evolution of an infarct follows a sequence:

1. 12 to 24 hours: red (eosinophilic) neurons.
2. 24 to 72 hours: neutrophils.
3. 3 to 5 days onward: macrophages (gitter cells) remove debris.
4. Weeks: reactive gliosis around a fluid-filled liquefactive cavity.

Hemorrhagic stroke:

• Intracerebral hemorrhage: usually hypertensive. It affects the basal ganglia (putamen), thalamus, pons and cerebellum, from rupture of Charcot-Bouchard microaneurysms. Lobar hemorrhages in older adults suggest cerebral amyloid angiopathy.
• Subarachnoid hemorrhage: most often from rupture of a saccular (berry) aneurysm at the anterior circle of Willis (anterior communicating artery). These aneurysms are associated with ADPKD and Ehlers-Danlos syndrome. The patient has a sudden "worst headache of my life" and neck stiffness. Vasospasm follows days later.
• Arteriovenous malformations bleed in young adults and cause seizures.

Traumatic hemorrhage:

• Epidural hematoma: temporal bone fracture tears the middle meningeal artery. There is a lucid interval, then rapid deterioration. CT shows a biconvex (lens-shaped) collection that does not cross suture lines.
• Subdural hematoma: torn bridging veins. It is common in the elderly, alcoholics and shaken infants. CT shows a crescent-shaped collection that crosses sutures. It can be chronic.
• Contusions occur at the coup and contrecoup sites, typically the frontal and temporal poles. Diffuse axonal injury follows rotational acceleration.

Cerebral edema, hydrocephalus and herniation

Edema:

• Vasogenic edema comes from a disrupted blood-brain barrier (tumor, abscess, inflammation). It is mainly in the white matter and responds to corticosteroids for tumors.
• Cytotoxic edema comes from cell injury (ischemia, hypoxia) and causes intracellular swelling.
• Interstitial (hydrocephalic) edema comes from CSF leaking across the ventricular lining.

Hydrocephalus:

• Non-communicating (obstructive): for example aqueductal stenosis, a fourth ventricle tumor, or tuberculous meningitis.
• Communicating: impaired absorption after meningitis or subarachnoid hemorrhage.
• Normal pressure hydrocephalus in older adults causes the triad of dementia, gait apraxia and urinary incontinence ("wacky, wobbly and wet").
• Hydrocephalus ex vacuo is passive ventricular enlargement from brain atrophy, not true hydrocephalus.

Raised intracranial pressure causes headache, vomiting, papilledema and the Cushing triad (hypertension, bradycardia, irregular respiration).

CNS infections

Degenerative and demyelinating diseases

• Alzheimer disease: the most common dementia. There is cortical atrophy of the hippocampus, temporal and parietal lobes, with extracellular beta-amyloid (neuritic) plaques, intracellular neurofibrillary tangles (hyperphosphorylated tau) and amyloid angiopathy. Early-onset forms are linked to APP (chromosome 21, which explains early Alzheimer disease in Down syndrome), PSEN1 and PSEN2; the late-onset risk allele is APOE e4.
• Vascular dementia: multiple infarcts or small-vessel disease; stepwise decline.
• Lewy body dementia: fluctuating cognition, visual hallucinations and parkinsonism.
• Frontotemporal dementia (Pick disease): personality change with Pick bodies (tau).
• Parkinson disease: loss of pigmented neurons in the substantia nigra (pallor of the substantia nigra), with Lewy bodies (alpha-synuclein).
• Huntington disease: CAG repeats with caudate atrophy and dilated lateral ventricles. It causes chorea and dementia.
• Amyotrophic lateral sclerosis: degeneration of upper and lower motor neurons (a SOD1 mutation in some familial cases). It causes mixed UMN and LMN signs with sparing of sensation and eye movements.
• Multiple sclerosis: autoimmune demyelination with periventricular plaques of differing ages. It is relapsing-remitting, with optic neuritis, internuclear ophthalmoplegia and oligoclonal bands in the CSF. It is uncommon in Filipinos.
• Others:
  • Guillain-Barré syndrome (peripheral demyelination, albuminocytologic dissociation) is covered in Medicine.
  • Wernicke encephalopathy (thiamine deficiency) damages the mammillary bodies.
  • Subacute combined degeneration (vitamin B12 deficiency) affects the dorsal columns and corticospinal tracts.
  • Central pontine myelinolysis follows overly rapid correction of hyponatremia.

CNS tumors

Brain tumors in adults are mostly supratentorial; in children they are mostly infratentorial (posterior fossa).