9.2 Epilepsy, Headache & Movement Disorders
Key Takeaways
- Sodium valproate is associated with a 10% risk of major congenital malformations and a 30-40% risk of neurodevelopmental delay; it is strictly contraindicated in female patients of childbearing potential unless a pregnancy prevention program (PULSE) is adhered to.
- In status epilepticus, first-line IV lorazepam 4 mg (or IM midazolam 10 mg) administered at 5 minutes terminates seizures in 60-70% of cases; failure to respond by 20 minutes mandates second-line IV levetiracetam (60 mg/kg), valproate (40 mg/kg), or fosphenytoin (20 mg PE/kg).
- Acute cluster headache attacks are treated with 100% high-flow oxygen (12-15 L/min via non-rebreather mask for 15 minutes) or subcutaneous sumatriptan 6 mg, achieving pain relief within 15 minutes in >80% of patients; verapamil (240-960 mg daily with baseline and follow-up ECG monitoring for PR prolongation) is the first-line prophylactic agent.
- Giant cell arteritis (GCA) requires immediate administration of high-dose corticosteroids (IV methylprednisolone 1 g daily for 3 days if visual loss, or oral prednisolone 60 mg daily) prior to obtaining a temporal artery biopsy to prevent irreversible ischemic optic neuropathy.
- In Parkinson's disease, initiating dopamine receptor agonists (pramipexole, ropinirole) carries a 15-20% cumulative risk of impulse control disorders (pathological gambling, hypersexuality, compulsive buying), requiring routine baseline and follow-up screening.
9.2 Epilepsy, Headache & Movement Disorders
This section covers the practical classification of seizures, evidence-based anti-seizure drug selection, emergency management of status epilepticus, differential diagnosis and management of primary and secondary headache disorders, and clinical evaluation of parkinsonian and hyperkinetic movement disorders for the MRCPI examination.
Epilepsy & Anti-Seizure Medications (ASMs)
Seizures are classified according to the 2017 International League Against Epilepsy (ILAE) framework into focal onset (focal aware, focal impaired awareness; motor vs. non-motor), generalized onset (absence, myoclonic, tonic-clonic, atonic), and unknown onset.
First-Line Anti-Seizure Drug Selection
• Focal Seizures: First-line agents include Lamotrigine or Levetiracetam. Second-line options include Carbamazepine, Lacosamide, or Oxcarbazepine. • Generalized Tonic-Clonic Seizures: First-line agents include Sodium Valproate (in males and post-menopausal females), Lamotrigine, or Levetiracetam. • Absence Seizures: Ethosuximide is the first-line choice for isolated absence seizures; Sodium Valproate is used if absence seizures coexist with generalized tonic-clonic seizures. Carbamazepine and Phenytoin exacerbate absence and myoclonic seizures and must be avoided.
| Anti-Seizure Medication | Primary Mechanism of Action | Major Adverse Effects & Toxicity | High-Yield MRCPI Exam Facts |
|---|---|---|---|
| Carbamazepine | Voltage-gated Na⁺ channel blocker | Hyponatremia (SIADH-like effect), leukopenia, diplopia, ataxia, Stevens-Johnson syndrome (SJS) | Potent hepatic CYP3A4 inducer. Screen for HLA-B*1502 allele in patients of Asian ancestry prior to initiation due to severe SJS/TEN risk. |
| Sodium Valproate | Broad-spectrum: enhances GABA, blocks Na⁺ channels and T-type Ca²⁺ channels | Weight gain, fine tremor, alopecia, hyperammonemic encephalopathy, acute pancreatitis, hepatotoxicity | Teratogenicity: 10% risk of major congenital malformations (neural tube defects) and 30-40% risk of neurodevelopmental delay. Contraindicated in females of childbearing potential unless strict pregnancy prevention program (PULSE) criteria are met. |
| Phenytoin | Voltage-gated Na⁺ channel blocker | Gingival hyperplasia, hirsutism, coarse facial features, peripheral neuropathy, cerebellar atrophy, megaloblastic anemia | Exhibits zero-order (saturation) kinetics at therapeutic plasma concentrations (10-20 mg/L). Small dose increments cause disproportionate increases in serum concentration. |
| Levetiracetam | Synaptic vesicle protein 2A (SV2A) ligand | Behavioral changes (agitation, irritability, depression, psychosis), somnolence | Excreted largely unchanged by the kidneys; dose adjustment required in renal impairment. Low drug interaction potential. |
| Lamotrigine | Voltage-gated Na⁺ channel blocker | Severe cutaneous adverse reactions (SJS/TEN), insomnia, tremor | Clear-cut drug interaction: Valproate inhibits lamotrigine metabolism, requiring a >50% reduction in lamotrigine starting dose with slow, extended titration. |
| Topiramate | AMPA/kainate receptor antagonist, Na⁺ blocker, carbonic anhydrase inhibitor | Weight loss, cognitive slowing ("dopamax"), nephrolithiasis, acute angle-closure glaucoma | Carbonic anhydrase inhibition causes metabolic acidosis and calcium phosphate renal stones. Induces CYP3A4 at higher doses. |
Status Epilepticus Management Protocol
Status epilepticus is defined clinically as continuous seizure activity lasting ≥5 minutes, or two or more discrete seizures without complete recovery of consciousness between episodes. Neuronal damage begins after 30 minutes of continuous seizure activity (t₂).
[0 - 5 Minutes: Initial Assessment & Stabilization]
• Assess airway, breathing, circulation, high-flow oxygen.
• Check capillary blood glucose; if <4.0 mmol/L, give 50 mL 50% glucose IV (+ Thiamine 250 mg IV if alcohol abuse suspected).
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[5 - 20 Minutes: First-Line Emergency Therapy]
• IV Lorazepam 4 mg over 2 mins (repeat once at 10 mins if seizures continue), OR
• IM Midazolam 10 mg (if no IV access), OR
• IV Diazepam 10 mg.
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[20 - 40 Minutes: Second-Line Urgent Control]
• IV Levetiracetam 60 mg/kg (max 4500 mg) infused over 10 mins, OR
• IV Sodium Valproate 40 mg/kg (max 3000 mg) infused over 10 mins, OR
• IV Fosphenytoin 20 mg PE/kg (max 1500 mg PE) with ECG monitoring.
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[>40 Minutes: Third-Line Refractory Status Epilepticus]
• Transfer to Intensive Care Unit (ICU).
• General anesthesia with continuous IV infusion of Propofol, Midazolam, or Thiopental under continuous EEG monitoring.
Primary & Secondary Headache Disorders
Migraine
• Clinical Presentation: Unilateral, throbbing headache lasting 4 to 72 hours, aggravated by routine physical activity, accompanied by nausea, vomiting, photophobia, and phonophobia. Aura occurs in 25% (typical aura consists of progressive visual scotoma, fortification spectra, or sensory paresthesias developing over 5-20 minutes). • Acute Treatment: Stepwise approach using NSAIDs (Naproxen 500 mg) or paracetamol combined with a 5-HT₁ᴮ/₁ᴰ agonist (Triptans: Sumatriptan 50-100 mg oral or 6 mg SC). Contraindications to triptans: Ischemic heart disease, previous stroke/TIA, coronary vasospasm, and uncontrolled hypertension. • Prophylaxis (indicated if ≥2 disabling attacks per month): Propranolol (80-160 mg daily), Topiramate (50-100 mg daily), Amitriptyline (10-50 mg nightly), or anti-CGRP monoclonal antibodies (Erenumab, Fremanezumab).
Cluster Headache
• Clinical Presentation: Strictly unilateral, excruciating periorbital or temporal pain lasting 15 to 180 minutes, occurring from once every other day up to 8 times daily. Associated with ipsilateral cranial autonomic signs: lacrimation, rhinorrhea, nasal congestion, miosis, ptosis (partial Horner syndrome), eyelid edema, and marked agitation/restlessness (patients pace the room). • Acute Therapy: 100% High-Flow Oxygen (12-15 L/min via non-rebreather mask for 15 minutes) or Subcutaneous Sumatriptan 6 mg. (Oral triptans act too slowly). • Prophylaxis: Verapamil (240-960 mg daily). Baseline and titration ECGs are mandatory to monitor for PR interval prolongation and heart block.
Giant Cell Arteritis (GCA)
• Clinical Presentation: Systemic vasculitis affecting medium and large arteries in individuals aged >50 years. Symptoms include new localized temporal headache, scalp tenderness (pain on combing hair), jaw claudication (pain on chewing; high specificity), visual loss (due to anterior ischemic optic neuropathy), and features of polymyalgia rheumatica. • Laboratory & Diagnostics: Inflammatory markers are markedly elevated: ESR >50 mm/hr (often >100 mm/hr) and CRP >20 mg/L. Temporal artery ultrasound shows "halo sign." Golden standard diagnostic test is Temporal Artery Biopsy (showing segmental transmural granulomatous inflammation with multinucleated giant cells). • Emergency Management: Immediate high-dose systemic corticosteroids must be administered prior to temporal artery biopsy to prevent permanent, irreversible blindness. Give IV Methylprednisolone 1 g daily for 3 days if acute visual loss is present; otherwise give oral Prednisolone 60 mg daily immediately.
Idiopathic Intracranial Hypertension (IIH)
• Clinical Presentation: Classically affects young, overweight females. Symptoms include progressive headache (worse lying flat and on coughing), transient visual obscurations (bouts of graying out of vision with posture changes), pulsatile tinnitus, papilloedema, and abducens nerve (CN VI) palsy causing binocular horizontal diplopia. • Diagnosis: Neuroimaging (MRI brain and MR venogram) demonstrates normal brain parenchyma with signs of raised ICP (empty sella, flattening of posterior sclera, distension of perioptic subarachnoid space) and rules out venous sinus thrombosis. Lumbar puncture demonstrates an elevated CSF opening pressure >25 cmH₂O with completely normal CSF cell count and biochemistry. • Management: Weight loss, Acetazolamide (500 mg to 2 g daily). Surgical interventions for refractory cases or progressive visual field loss include optic nerve sheath fenestration or ventriculoperitoneal shunt placement.
Movement Disorders
Parkinson's Disease
• Cardinal Clinical Triad:
- Bradykinesia: Slowness of movement with progressive decrement in speed and amplitude during repetitive hand movements (finger tapping). Essential feature.
- Resting Tremor: Asymmetric 4 to 6 Hz "pill-rolling" tremor, prominent at rest and suppressed during voluntary movement.
- Rigidity: Increased tone independent of velocity, exhibiting "cogwheel" (tremor superimposed on tone) or "lead-pipe" quality. • Clinical Hallmark: Asymmetric onset of motor symptoms. Non-motor features precede motor onset by years (hyposmia, REM sleep behavior disorder, constipation, depression). • Pharmacotherapy: • Levodopa + Dopa-Decarboxylase Inhibitor (Carbidopa or Benserazide): Most effective symptomatic therapy. Long-term use (>5 years) causes motor fluctuations (on-off phenomena) and dyskinesias. • Dopamine Agonists (Pramipexole, Ropinirole): Direct post-synaptic D₂/D₃ agonists. Lower risk of dyskinesias in younger patients, but carry a 15-20% risk of impulse control disorders (pathological gambling, hypersexuality, compulsive spending/binge eating). • MAO-B Inhibitors (Rasagiline, Selegiline): Mild symptomatic benefit; block central dopamine breakdown. • COMT Inhibitors (Entacapone): Prevent peripheral levodopa degradation; must be co-administered with levodopa.
Essential Tremor vs. Huntington's Disease vs. PSP
• Essential Tremor: High-frequency (4-12 Hz) bilateral, symmetrical postural and kinetic (action) tremor of hands, head, or voice. Absence of bradykinesia or rigidity. Dramatically improves with alcohol. First-line therapy: Propranolol or Primidone. • Huntington's Disease: Autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion (>40 repeats) in the HTT gene on chromosome 4p, demonstrating anticipation (earlier, more severe presentation in successive generations, especially via paternal transmission). Clinical triad: Chorea, progressive dementia, and psychiatric disease. MRI shows bilateral atrophy of the caudate nuclei with enlargement of the frontal horns of the lateral ventricles ("box-car ventricles"). • Progressive Supranuclear Palsy (PSP): Atypical parkinsonian tauopathy characterized by vertical supranuclear gaze palsy (downward gaze limitation is pathognomonic), early axial rigidity, frequent early backward falls, and retrocollis.
A 72-year-old man presents to the emergency department with a 5-day history of a severe right-sided temporal headache, malaise, and pain in his jaw when chewing tough food. Over the past 2 hours, he has noticed sudden blurring of vision in his right eye. On examination, the right temporal artery is tender and nodular with reduced pulsation. Fundoscopy reveals right optic disc swelling. ESR is 102 mm/hr. What is the most appropriate immediate management step?
A 34-year-old man with focal impaired awareness epilepsy who was started on an anti-seizure medication 6 weeks ago presents to his outpatient clinic complaining of double vision, unsteady gait, and lethargy. Routine laboratory investigations reveal a serum sodium level of 124 mmol/L (135-145 mmol/L) and a white blood cell count of 3.1 x 10^9/L (4.0-11.0 x 10^9/L). Which anti-seizure medication is most likely responsible for these clinical and laboratory findings?
A 42-year-old man presents with recurring attacks of excruciating, sharp pain behind his left eye that wake him from sleep at night. The attacks last 45 to 60 minutes and occur twice daily. During each attack, his left eye waters profusely, his left nostril becomes congested, and he feels extremely restless, pacing around the room. What is the most effective initial acute therapy to terminate these attacks?