10.4 Seizures, Epilepsy & Movement Disorders
Key Takeaways
- Seizures is a named blueprint subsection, and movement disorders separately enumerates Parkinson disease, essential tremor and other movement disorders.
- Valproate carries the highest teratogenic and neurodevelopmental risk and is avoided in people who may become pregnant.
- Benzodiazepines are the first-line abortive therapy in status epilepticus, followed promptly by a second-line antiseizure medication.
- A resting pill-rolling tremor that improves with action indicates parkinsonism, while a postural and action tremor that improves with alcohol indicates essential tremor.
- Normal pressure hydrocephalus presents with gait apraxia, urinary incontinence and cognitive slowing, and large-volume lumbar puncture predicts shunt response.
Last updated: August 2026
1. Epilepsy & Antiseizure Medication (ASM) Selection
Seizure Classification (ILAE 2017)
- Focal Onset Seizures: Originate within neuronal networks limited to one cerebral hemisphere.
- Focal Aware (Simple Partial): Consciousness and awareness are fully preserved.
- Focal Impaired Awareness (Complex Partial): Consciousness is altered; frequently accompanied by automatisms (lip-smacking, chewing, hand fumbling) and followed by post-ictal confusion.
- Focal Motor vs Non-motor: May evolve into bilateral tonic-clonic convulsions (secondary generalization).
- Generalized Onset Seizures: Originate simultaneously across bilateral cerebral hemispheres.
- Generalized Motor: Bilateral symmetric tonic-clonic convulsions with loss of consciousness, tongue biting (lateral border), urinary incontinence, and prolonged post-ictal stertorous respiration.
- Generalized Non-motor (Absence Seizures / Petit Mal): Sudden, brief (5-10 second) lapses of consciousness with vacant staring and unresponsiveness, immediate return to baseline without post-ictal confusion; provoked by hyperventilation; classic EEG shows bilateral 3-Hz spike-and-wave discharges.
First Unprovoked Seizure Evaluation & When to Treat
- Diagnostic Workup: Comprehensive metabolic panel, toxicology screen, 12-lead ECG, Brain MRI with dedicated epilepsy protocol (evaluating for hippocampal/mesial temporal sclerosis, focal cortical dysplasia, cavernous hemangioma, low-grade neoplasm), and routine 20-30 min wake/sleep EEG.
- Treatment Threshold (ILAE Definition of Epilepsy): Antiseizure medications (ASMs) are generally NOT initiated after a single unprovoked seizure with normal MRI, normal EEG, and no focal deficit (recurrence risk ~30%). Treatment is initiated if the recurrence risk is >60% over the next 10 years, meeting criteria for epilepsy:
- Two unprovoked seizures occurring >24 hours apart.
- A single unprovoked seizure in the setting of: (a) Epileptiform discharges on EEG; (b) A structural epileptogenic brain lesion on MRI (e.g., prior stroke, tumor, cortical scar); or (c) Nocturnal seizure occurrence.
Antiseizure Medication Selection & High-Yield Toxicities
| Seizure Type | First-Line ASMs | Alternative ASMs | High-Yield Board Adverse Effects & Clinical Warnings |
|---|---|---|---|
| Focal Onset Seizures (Aware or Impaired Awareness) | Levetiracetam, Lamotrigine, Lacosamide | Carbamazepine, Oxcarbazepine, Topiramate, Zonisamide | - Levetiracetam: Neuropsychiatric changes (irritability, aggression, depression, psychosis)<br/>- Lamotrigine: Stevens-Johnson syndrome (SJS) / TEN; requires slow dose titration. Estrogen-containing OCPs double clearance<br/>- Lacosamide: PR prolongation, first-degree AV block, syncope<br/>- Carbamazepine / Oxcarbazepine: Hyponatremia / SIADH, agranulocytosis, aplastic anemia, CYP3A4 induction. Mandatory HLA-B*1502 screening in Asian ancestry to prevent SJS/TEN |
| Generalized Tonic-Clonic Seizures | Levetiracetam, Lamotrigine, Valproic Acid / Divalproex | Topiramate, Zonisamide, Brivaracetam | - Valproic Acid: Black box warning for severe teratogenicity (neural tube defects, lower IQ); weight gain, alopecia, tremor, hepatotoxicity, pancreatitis, hyperammonemic encephalopathy. Strictly avoided in females of childbearing potential |
| Absence Seizures | Ethosuximide | Valproic Acid | - Ethosuximide: Selectively blocks T-type Ca2+ channels in thalamic neurons. Side effects: nausea, vomiting, lethargy. Avoid sodium channel blockers (Carbamazepine, Phenytoin) which paradoxically worsen absence seizures |
2. Movement Disorders: Parkinson Disease, Essential Tremor & NPH
1. Parkinson Disease (PD)
- Pathophysiology: Progressive loss of dopaminergic neurons in the substantia nigra pars compacta, resulting in dopamine depletion in the striatum (caudate and putamen) and disrupted basal ganglia circuitry. Histopathology reveals intracellular Lewy bodies containing aggregated alpha-synuclein.
- Cardinal Motor Triad (TRAP):
- T — Tremor: Asymmetric 4 to 6 Hz resting tremor ("pill-rolling"), most prominent in hands/fingers; present at rest, decreases/disappears with purposeful voluntary action and during sleep.
- R — Rigidity: Velocity-independent resistance to passive limb movement; characterized as "cogwheel" (superimposed tremor on increased muscle tone) or "lead-pipe" rigidity.
- A — Akinesia / Bradykinesia: Slowness of movement initiation and decrementing amplitude/speed with repetitive movements (finger tapping, foot tapping); masked facies (hypomimia), decreased spontaneous blink rate, soft monotonic speech (hypophonia), micrographic handwriting, and a shuffling, short-stepped festinating gait with reduced arm swing and en bloc turning.
- P — Postural Instability: Manifests late in disease course; impaired righting reflexes (positive pull test) leading to frequent unprovoked falls.
- Non-Motor Clinical Features:
- REM Sleep Behavior Disorder (RBD): Loss of normal motor atonia during REM sleep causing vivid dream enactment (punching, kicking, flailing); characteristically precedes motor symptoms by 10 to 20 years.
- Anosmia / Hyposmia (loss of smell), chronic constipation, orthostatic hypotension, urinary urgency, depression, anxiety, apathy.
- Parkinson Disease Dementia (PDD): Cognitive decline and visual hallucinations developing > 1 year AFTER established motor parkinsonism (contrasted with Dementia with Lewy Bodies [DLB], in which dementia occurs prior to or concurrently within 1 year of parkinsonian motor signs).
Pharmacotherapy of Parkinson Disease
- Levodopa-Carbidopa (Sinemet):
- Mechanism: Levodopa crosses the blood-brain barrier and is converted to dopamine by central DOPA decarboxylase; Carbidopa inhibits peripheral DOPA decarboxylase, preventing peripheral conversion and minimizing nausea, vomiting, and cardiac arrhythmias.
- Efficacy: The single most effective medication for motor symptom control.
- Long-Term Complications (after 5-10 years): Motor fluctuations ("wearing-off" phenomenon between doses, sudden unpredictable "on-off" fluctuations) and peak-dose dyskinesias (choreoathetotic movements).
- Dopamine Receptor Agonists (Pramipexole, Ropinirole, Rotigotine):
- Directly stimulate post-synaptic D2/D3 receptors. Used as initial monotherapy in younger patients (<65 years) to delay levodopa-induced motor complications.
- Critical Board Side Effects: Impulse Control Disorders (pathological gambling, hypersexuality, compulsive shopping/binge eating in up to 15-20% of patients), sudden "sleep attacks" (excessive daytime somnolence), orthostatic hypotension, and peripheral edema.
- MAO-B Inhibitors (Rasagiline, Selegiline, Safinamide): Irreversibly inhibit central dopamine metabolism; provide modest motor symptom relief.
- COMT Inhibitors (Entacapone, Opicapone): Inhibit catechol-O-methyltransferase, prolonging levodopa half-life. Administered strictly in combination with levodopa to treat "wearing-off" fluctuations. Causes harmless orange-brown urine discoloration and diarrhea.
- Anticholinergic Agents (Trihexyphenidyl, Benztropine): Centrally acting antimuscarinics effective for prominent resting tremor in younger patients (<65y). Strictly contraindicated in elderly patients due to severe confusion, hallucinations, memory impairment, urinary retention, and acute angle-closure glaucoma.
- Amantadine: NMDA receptor antagonist; primarily utilized to suppress levodopa-induced dyskinesias. Side effects: livedo reticularis and ankle edema.
- Deep Brain Stimulation (DBS): High-frequency electrical stimulation of the Subthalamic Nucleus (STN) or Globus Pallidus internus (GPi). Indicated for patients with idiopathic PD who have excellent levodopa responsiveness but suffer from severe, disabling medication-refractory motor fluctuations, dyskinesias, or medication-refractory tremor, provided they have no severe dementia or active psychiatric illness.
2. Essential Tremor (ET) vs Parkinson Disease Tremor
| Clinical Feature | Essential Tremor (ET) | Parkinson Disease (PD) Tremor |
|---|---|---|
| Tremor Type | Postural and Kinetic (Action) Tremor | Resting Tremor |
| Frequency | 6 to 12 Hz (faster, fine) | 4 to 6 Hz (slower, coarse "pill-rolling") |
| Anatomical Distribution | Bilateral and symmetric; hands, forearms, head (horizontal "no-no" or vertical "yes-yes" titubation), voice | Asymmetric onset; hands, fingers, legs, chin/lips; strictly spares the head |
| Relation to Movement | Worsens during voluntary movement (finger-to-nose, holding arms outstretched, drinking from a cup, writing) | Present at rest; attenuates or disappears with purposeful movement |
| Associated Features | No bradykinesia, no rigidity, normal gait, normal posture | Bradykinesia, cogwheel rigidity, masked facies, shuffling festinating gait |
| Alcohol Response | Transiently improves with small amounts of alcohol | No consistent improvement with alcohol |
| Family History | Autosomal dominant in >50% (familial tremor) | Mostly sporadic (~10% familial) |
| First-Line Medical Therapy | Propranolol (60-240 mg/day) OR Primidone (50-750 mg/day) | Levodopa-Carbidopa, Dopamine Agonists, Trihexyphenidyl |
| Surgical Therapy | DBS of the Ventral Intermediate (VIM) Nucleus of the Thalamus | DBS of Subthalamic Nucleus (STN) or Globus Pallidus internus (GPi) |
3. Normal Pressure Hydrocephalus (NPH)
- Pathophysiology: Impaired cerebrospinal fluid resorption through arachnoid villi/granulations leading to chronic ventriculomegaly with normal or intermittently elevated opening pressures. The expanding ventricles stretch periventricular corticospinal motor fibers and frontal-subcortical circuits.
- Classic Clinical Triad ("Wet, Wacky, and Wobbly"):
- Gait Apraxia / Disturbance ("Wobbly"): The earliest, most prominent, and most reversible feature. Described as a wide-based, short-stepped, slow, shuffling "magnetic gait" (feet appear glued to the floor with difficulty lifting legs and severe hesitation on turning).
- Urinary Incontinence ("Wet"): Starts as urinary urgency and frequency, progressing to frank urge incontinence due to detrusor hyperreflexia and loss of cortical frontal inhibition.
- Cognitive Decline / Subcortical Dementia ("Wacky"): Psychomotor slowing, apathy, inattention, executive dysfunction, and memory retrieval deficits with preserved recognition cues.
- Diagnostic Evaluation:
- Brain MRI or CT: Symmetrical enlargement of the lateral and third ventricles out of proportion to cerebral cortical sulcal atrophy; Evans Index > 0.30 (ratio of maximal frontal horn diameter to maximal internal skull diameter); narrow callosal angle (<90°); periventricular transependymal CSF transudation.
- High-Volume Lumbar Puncture (CSF Tap Test): Removal of 30 to 50 mL of CSF with objective quantitative measurement of gait speed, stride length, and cadence before and 30-60 minutes after the tap. Improvement in gait metrics confirms NPH and predicts excellent surgical response.
- Definitive Treatment: Ventriculoperitoneal (VP) Shunting (or ventriculopleural shunt). Provides long-term improvement in gait in >80% of properly selected patients.
Test Your Knowledge
A 26-year-old woman presents to the clinic for management of newly diagnosed focal epilepsy with impaired awareness and secondary generalization. She is newly married and plans to start a family within the next year. Her neurological exam is normal and brain MRI is unremarkable. Routine EEG demonstrated focal left temporal sharp waves. In counseling this patient regarding antiseizure medication selection, which of the following agents is most appropriate as first-line monotherapy, while minimizing the risk of major congenital malformations?
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Test Your Knowledge
A 52-year-old man with a history of alcohol use disorder is brought to the emergency department in active convulsive status epilepticus. Emergency medical services witnessed continuous generalized tonic-clonic activity that has persisted for 8 minutes despite administration of a single 4-mg dose of IV Lorazepam. On arrival, he remains in continuous generalized convulsion. His airway is secured with supplemental oxygen, blood pressure is 148/88 mmHg, heart rate is 124 bpm, and point-of-care blood glucose is 92 mg/dL. What is the most appropriate next step in pharmacological management?
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Test Your Knowledge
A 71-year-old retired architect is accompanied by his spouse to the clinic because of a 10-month history of progressive difficulty walking. His spouse notes that he takes very small, slow steps and appears to have his feet 'stuck to the floor', resulting in several recent falls. Over the past 4 months, he has also developed urgent urinary frequency with several episodes of involuntary bedwetting, as well as noticeable psychomotor slowing, apathy, and forgetfulness. On examination, he exhibits a wide-based, short-stepped shuffling gait with difficulty initiating forward movement, but there is no resting tremor, cogwheel rigidity, or sensory loss. Brain MRI demonstrates marked symmetric lateral and third ventriculomegaly with an Evans index of 0.36 and minimal cortical sulcal atrophy. What is the most appropriate next step in the diagnostic and therapeutic management of this patient?
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