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Seizures, Headache & Demyelination

Name: Seizures, Headache & Demyelination
Creator: Veli Bakalov, MD

Classifying seizures, the primary headaches, and when pressure or myelin is the problem

Neurology & Psychiatry·Neuropathology·6 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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Focal impaired awareness (complex partial) seizures usually arise in the temporal lobe: staring, lip-smacking automatisms, postictal confusion; generalized seizures involve both hemispheres from onset.
Absence seizures = brief staring, 3-Hz spike-and-wave, no postictal state; ethosuximide (thalamic T-type Ca2+ blocker) is first-line, and carbamazepine or phenytoin can worsen them.
Infantile spasms (West syndrome) = hypsarrhythmia, tuberous sclerosis, ACTH or vigabatrin; juvenile myoclonic epilepsy = morning myoclonic jerks, valproate (teratogenic: neural tube defects).
Status epilepticus (≥5 min, or recurrent seizures without recovery): IV lorazepam first, then load fosphenytoin, levetiracetam, or valproate; refractory cases get propofol or midazolam anesthesia.
Migraine = unilateral pulsating 4–72 h with nausea and photophobia (triptans; prevent with propranolol, topiramate, amitriptyline, CGRP antibodies); tension-type = bilateral band, most common primary headache.
Cluster = excruciating periorbital pain for 15 min–3 h with lacrimation, rhinorrhea, and partial Horner in a restless man: 100% oxygen or SC sumatriptan acutely, verapamil to prevent.
Thunderclap headache = subarachnoid hemorrhage until proven otherwise (noncontrast CT, then LP for xanthochromia); giant cell arteritis needs steroids immediately to prevent blindness.
Cushing triad (hypertension with wide pulse pressure, bradycardia, irregular respirations) signals raised ICP; uncal herniation compresses CN III (fixed dilated pupil, down and out) and the PCA.
NPH = wet, wobbly, wacky with normal opening pressure (VP shunt); MS = CNS demyelination in space and time with oligoclonal bands; Guillain-Barré = PNS demyelination after Campylobacter, treat with IVIG or plasmapheresis.

Classifying seizures and epilepsy syndromes

Focal vs generalized. Focal (partial) seizures begin in one hemisphere. In a focal aware seizure (formerly simple partial) consciousness is preserved. A focal impaired awareness seizure (formerly complex partial) usually comes from the temporal lobe: the patient stares, shows automatisms such as lip-smacking, and is confused afterward. Any focal seizure can secondarily generalize. Generalized seizures involve both hemispheres from the start and usually impair consciousness (awareness is typically preserved in myoclonic seizures). Mesial temporal (hippocampal) sclerosis is the classic lesion in adult temporal lobe epilepsy.

Generalized seizure types.

Tonic-clonic (grand mal): stiffening followed by jerking, with tongue-biting, incontinence, and postictal confusion.
Absence (petit mal): children; brief staring spells, 3-Hz spike-and-wave on EEG, no postictal state. Hyperventilation can provoke them.
Myoclonic: quick, shock-like jerks. Atonic: sudden loss of tone (drop attacks). Tonic: stiffening alone.

Age points to the syndrome.

Infantile spasms (West syndrome): hypsarrhythmia on EEG; linked to tuberous sclerosis; treat with ACTH or vigabatrin.
Childhood absence epilepsy: 3-Hz spike-and-wave; ethosuximide.
Juvenile myoclonic epilepsy: myoclonic jerks in the morning, often provoked by sleep deprivation; valproate.
Febrile seizures: 6 months to 5 years. Simple febrile seizures (generalized, shorter than 15 minutes, not repeated within 24 hours) are benign.

Antiseizure drugs and status epilepticus

Antiseizure drugs in this topic

Drug	Mechanism	Main use	Classic toxicity
Ethosuximide	Blocks thalamic T-type Ca²⁺ channels	First-line for childhood absence; does not cover tonic-clonic seizures	GI upset, fatigue, headache; rarely Stevens-Johnson syndrome
Valproate	↑ Na⁺ channel inactivation, ↑ GABA	Broad spectrum: absence, tonic-clonic, myoclonic	Neural tube defects, hepatotoxicity, pancreatitis, weight gain, tremor
Phenytoin / fosphenytoin	Na⁺ channel blockade	Focal and tonic-clonic seizures; second step in status	Gingival hyperplasia, hirsutism, nystagmus, ataxia, fetal hydantoin syndrome
Carbamazepine	Na⁺ channel blockade	Focal seizures; trigeminal neuralgia	Agranulocytosis, SIADH, SJS (HLA-B*1502), CYP450 induction
Levetiracetam	Binds synaptic vesicle protein SV2A	Broad spectrum; second step in status	Irritability and mood change
Lorazepam, midazolam	↑ Frequency of GABA_A Cl⁻ channel opening	First-line to abort status	Sedation, respiratory depression

Carbamazepine and phenytoin can worsen absence seizures, so avoid them in absence epilepsy.

Valproate covers every generalized type, but its neural tube defect risk makes it a poor choice in pregnancy.

Status epilepticus. A seizure lasting 5 minutes or longer, or recurrent seizures without recovery in between, is an emergency. Protect the airway and check glucose while treatment escalates:

IV benzodiazepineLorazepam is first-line; IM midazolam or rectal diazepam if there is no IV access.
Load a longer-acting antiseizure drugFosphenytoin, levetiracetam, or valproate.
Refractory statusGeneral anesthesia with propofol or a midazolam infusion.

Primary headaches

Migraine, cluster, and tension-type headache

Feature	Migraine	Cluster	Tension-type
Pain	Unilateral, pulsating, worse with activity	Excruciating, unilateral periorbital	Bilateral, band-like, pressing; mild to moderate
Duration	4–72 h	15 min–3 h, recurring in clusters	Variable; may be constant
Associated	Photophobia, phonophobia, nausea; aura (scintillating scotoma) in a minority	Ipsilateral lacrimation, rhinorrhea, conjunctival injection, partial Horner (ptosis, miosis)	No nausea; not worsened by activity
Patient	Female predominance; lies still in a dark room	Male predominance; restless, paces	Most common primary headache
Acute therapy	Triptans (5-HT_1B/1D agonists) or NSAIDs	100% oxygen, subcutaneous sumatriptan	NSAIDs or acetaminophen
Prevention	Propranolol, topiramate, amitriptyline, CGRP antibodies	Verapamil	Amitriptyline

Migraine criteria, POUND: Pulsatile, One-day (4–72 h), Unilateral, Nausea, Disabling.

Migraine mechanism. Activation of the trigeminovascular system releases CGRP and other vasoactive neuropeptides such as substance P around meningeal vessels; the aura reflects cortical spreading depression. Triptans constrict cranial vessels and block neuropeptide release, so they are contraindicated in coronary artery disease and vasospastic (Prinzmetal) angina.

Cluster headache. Attacks recur at the same time of day for weeks, reflecting hypothalamic involvement. The Horner syndrome is partial (ptosis and miosis, facial sweating spared) because the sympathetic plexus is affected along the internal carotid.

Red-flag headaches, raised ICP, and hydrocephalus

Thunderclap headache ("worst of my life") is subarachnoid hemorrhage, usually from a ruptured berry aneurysm, until proven otherwise. Obtain a noncontrast CT; if negative, do an LP looking for xanthochromia. Berry aneurysms are linked to ADPKD, Ehlers-Danlos, and Marfan syndromes.
Giant cell arteritis: age over 50, jaw claudication, high ESR. Blindness is the danger, so start steroids immediately rather than waiting for biopsy.
Idiopathic intracranial hypertension: obese young woman with papilledema, high opening pressure, and normal imaging and CSF; treat with weight loss and acetazolamide.
Tumor: morning headache that worsens lying down.

Raised intracranial pressure. Normal ICP is 5–15 mmHg. Elevation causes headache worse lying down, morning vomiting, and papilledema. The Cushing triad (hypertension with a widened pulse pressure, bradycardia, and irregular respirations) signals brainstem compression. Uncal herniation pushes the medial temporal lobe against the tentorium, compressing CN III (fixed dilated pupil, eye down and out) and the PCA (contralateral homonymous hemianopia). Tonsillar herniation compresses the medulla and causes cardiorespiratory arrest.

Types of ventricular enlargement

Feature	Communicating	Noncommunicating (obstructive)	Ex vacuo
Defect	Poor CSF resorption at arachnoid granulations	Obstruction within the ventricular system	Brain atrophy; CSF fills the lost volume
Causes	Post-SAH, meningitis; includes NPH	Aqueductal stenosis, tumor, colloid cyst	Alzheimer disease, advanced HIV
Ventricles	All enlarge	Only those upstream of the block	Enlarged with widened sulci

Hydrocephalus ex vacuo is not true hydrocephalus: pressure is normal.

Normal pressure hydrocephalus is a communicating hydrocephalus of older adults with the triad "wet, wobbly, wacky": urinary incontinence, gait apraxia (magnetic gait), and dementia. Opening pressure is normal despite ventriculomegaly, which stretches periventricular (corona radiata) fibers. Improvement after a large-volume LP predicts benefit from a VP shunt, which can reverse the syndrome.

Demyelinating diseases

Multiple sclerosis. Autoimmune destruction of CNS myelin made by oligodendrocytes, typically in young women, with lesions disseminated in space and time. Classic findings:

Optic neuritis: painful monocular vision loss with a Marcus Gunn pupil (relative afferent pupillary defect).
Internuclear ophthalmoplegia from an MLF lesion: the ipsilateral eye cannot adduct on lateral gaze, the abducting eye shows nystagmus, and convergence is spared. Bilateral INO in a young adult suggests MS.
Lhermitte sign (electric shock down the spine on neck flexion) and Uhthoff phenomenon (heat worsens symptoms).
Classic triad: scanning speech, intention tremor, nystagmus.

MRI shows periventricular plaques radiating from the ventricles (Dawson fingers); CSF has oligoclonal IgG bands with a raised IgG index. Relapses are treated with high-dose corticosteroids; disease-modifying options include interferon-β, glatiramer, and natalizumab.

Other demyelinating disorders.

Osmotic demyelination (central pontine myelinolysis): overly rapid correction of hyponatremia injures pontine myelin, causing quadriparesis, dysarthria, dysphagia, and a locked-in state. "From low to high, your pons will die": correct chronic hyponatremia slowly.
Progressive multifocal leukoencephalopathy: JC virus infects oligodendrocytes in immunosuppressed patients (HIV, natalizumab), causing progressive multifocal white-matter deficits; the only treatment is restoring immunity.
Guillain-Barré syndrome: post-infectious demyelination of PNS (Schwann-cell) myelin, classically after Campylobacter jejuni, with ascending paralysis, areflexia, and albuminocytologic dissociation (high CSF protein, normal cell count). Treat with IVIG or plasmapheresis, not steroids.

Guillain-Barré can progress to respiratory failure, so track vital capacity.