17.1 Epilepsy & Acute Seizures

Epilepsy and acute seizures form one of the highest-yield topics in MRCP(UK) Part 1. Candidates must master clinical seizure classification, evidence-based antiepileptic drug (AED) selection according to NICE guidelines, unique AED pharmacokinetic and toxicological profiles, emergency status epilepticus management, and statutory UK DVLA driving regulations.

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1. ILAE 2017 Seizure Classification

The International League Against Epilepsy (ILAE 2017) classifies seizures based on three key levels: type of onset (focal, generalised, or unknown), awareness during the seizure (for focal seizures), and motor versus non-motor manifestations.

Focal Seizures

Focal seizures originate within neuronal networks limited to one cerebral hemisphere:

• Focal Aware Seizures (formerly Simple Partial): Consciousness and awareness remain fully intact throughout the event. Manifestations depend on the cortical locus:
  • Motor onset: Jacksonian march (clonic jerking spreading progressively along the motor strip homunculus), versive head/eye turning, vocalisation, or unilateral posturing.
  • Sensory onset: Parietal lobe origin producing contralateral paraesthesias, flashing lights (occipital), or olfactory/gustatory hallucinations (uncus).
  • Autonomic onset: Temporal lobe origin characteristically presenting with an epigastric rising sensation, flushing, diaphoresis, or pupillary changes.
  • Cognitive / Emotional onset: Temporal or limbic origin producing déjà vu, jamais vu, dreamy states, depersonalisation, micro/macropsia, or unprovoked sudden fear/panic.
• Focal Impaired Awareness Seizures (formerly Complex Partial): Consciousness or awareness is impaired or lost at any point during the seizure. Patients typically exhibit behavioral arrest, vacant staring, and automatisms (involuntary, repetitive, semi-purposeful motor behaviours such as lip smacking, chewing, swallowing, or manual fumbling), followed by post-ictal confusion and amnesia.
• Focal to Bilateral Tonic-Clonic (formerly Secondary Generalisation): Seizure activity initiates focally (often with a recognizable aura) before propagating across both cerebral hemispheres, terminating in a generalised tonic-clonic seizure.

Generalised Seizures

Generalised seizures originate simultaneously within bilaterally distributed cerebral networks from onset, with immediate impairment of consciousness:

• Generalised Tonic-Clonic (GTC): Sudden loss of consciousness, tonic phase (sustained axial and limb stiffening, ictal cry from forced expiration against closed vocal cords, respiratory arrest, cyanosis), followed by clonic phase (synchronous rhythmic jerking of all limbs, tongue biting—lateral border laceration is highly specific for epileptic seizure—and urinary incontinence). Followed by post-ictal flaccidity, stertorous breathing, deep sleep, headache, myalgias, and transient focal weakness (Todd's paresis).
• Absence Seizures (Petit Mal): Sudden, brief (5–15 seconds) behavioral arrest and unresponsiveness with immediate recovery, lacking post-ictal confusion. Classic EEG finding is synchronous 3 Hz generalized spike-and-wave discharges, frequently provoked by hyperventilation.
• Myoclonic Seizures: Sudden, brief (<100 milliseconds), shock-like involuntary muscle contractions without loss of consciousness. Prominent in Juvenile Myoclonic Epilepsy (JME).
• Atonic Seizures ("Drop Attacks"): Sudden loss of postural muscle tone lasting <2 seconds, precipitating traumatic falls, typically seen in severe epileptic encephalopathies (e.g. Lennox-Gastaut syndrome).

Juvenile Myoclonic Epilepsy (JME / Janz Syndrome)

• Idiopathic generalised epilepsy accounting for ~10% of all epilepsies, typically presenting between ages 12 and 18.
• Characterized by the clinical triad of: 1. Early morning bilateral myoclonic jerks (characteristically causing patients to drop cups, toothbrushes, or cutlery shortly after waking); 2. Generalised tonic-clonic seizures; 3. Typical absence seizures (in ~30%).
• Triggered by sleep deprivation, fatigue, alcohol consumption, and stroboscopic photic stimulation.
• EEG reveals generalized 4–6 Hz polyspike-and-wave discharges on a normal background.

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2. NICE Guideline-Directed Antiepileptic Drug (AED) Selection

NICE guidelines (NG217) provide clear hierarchies for initial AED monotherapy based on confirmed seizure semiology:

Valproate Safety Measures & Pregnancy Prevention Programme

• Teratogenicity Profile: Exposure to sodium valproate during pregnancy carries an exceptionally high risk of major congenital malformations in ~10% of infants (neural tube defects such as spina bifida [10-fold increase], congenital heart defects, cleft palate, and hypospadias) and neurodevelopmental disorders in 30–40% (autism spectrum disorders, ADHD, cognitive impairment, and reduced verbal IQ).
• Regulatory Mandate (MHRA & NICE): Valproate is strictly contraindicated in girls and women of childbearing potential unless no other antiepileptic is effective, and the patient is enrolled in the mandatory Valproate Pregnancy Prevention Programme (Prevent), utilizing highly effective long-acting reversible contraception (LARC) and signing an annual risk acknowledgement form. From 31 January 2024 the MHRA extended the restriction to men: valproate must not be started in any new patient under 55 years, male or female, unless two specialists independently agree and document that there is no other effective or tolerated treatment, or that there are compelling reasons why the reproductive risks do not apply. The measure was prompted by evidence of impaired male fertility as well as the established teratogenic risk. The MHRA subsequently clarified that a two-clinician annual review is not required for men already established on valproate; the two-specialist requirement applies to initiation in under-55s.

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3. High-Yield Antiepileptic Drug Pharmacology & Toxicities

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4. Emergency Management Protocol for Status Epilepticus

Status epilepticus is a medical emergency defined operationally as continuous convulsive seizure activity lasting >= 5 minutes, or two or more distinct seizures without full recovery of consciousness between episodes (T1 threshold = 5 min, initiating emergency therapy; T2 threshold = 30 min, beyond which long-term neuronal necrosis and excitotoxic damage occur).

Convulsive Seizure >= 5 Minutes (Status Epilepticus)
  │
  ├── STEP 1 (0–10 min): Immediate Bedside Stabilisation & First-Line Benzodiazepine
  │     ├── High-flow 15 L/min O2 via non-rebreather mask; maintain patent airway
  │     ├── Check capillary blood glucose (give IV 20% glucose + thiamine if hypoglycaemic)
  │     └── IV access: IV Lorazepam 4 mg bolus (slow over 2 min)
  │           (Pre-hospital / no IV access: Buccal Midazolam 10 mg OR Rectal Diazepam 10 mg)
  │           *If seizures continue after 10 min: repeat IV Lorazepam 4 mg ONCE*
  │
  ├── STEP 2 (10–30 min): Established Status — Second-Line IV Antiepileptic Infusion
  │     (If seizures persist >=10 min after second benzodiazepine dose; infuse over 10–15 min)
  │     ├── IV Levetiracetam: 60 mg/kg (max 4.5 g)  OR
  │     ├── IV Sodium Valproate: 40 mg/kg (max 3.0 g)  OR
  │     └── IV Phenytoin: 20 mg/kg (max rate 50 mg/min, continuous ECG/BP monitoring)
  │
  └── STEP 3 (30–60 min): Refractory Status Epilepticus — General Anaesthesia in ITU
        ├── Rapid sequence induction and endotracheal intubation
        ├── IV Anaesthetic agents: Propofol, Midazolam infusion, or Thiopental sodium
        └── Continuous EEG (cEEG) monitoring targeting electrographic burst suppression

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5. UK DVLA Statutory Fitness to Drive Regulations

Compliance with DVLA regulations is mandatory under UK law. Doctors have a professional duty to inform patients of their legal obligation to cease driving and notify the DVLA:

Group 1 Licenses (Cars and Light Motorcycles)

• Single Unprovoked Seizure: Must cease driving for a minimum of 6 months. Relicensing may be granted at 6 months if clinical assessment, brain MRI, and EEG demonstrate no significant ongoing epileptogenic risk (risk of recurrence <20% per annum).
• Established Epilepsy / Multiple Unprovoked Seizures: Must cease driving for a minimum of 12 continuous months seizure-free.
• Established Sleep-Only Seizures: May hold a license if a consistent pattern of seizures occurring exclusively during sleep has been established for at least 1 year without any waking seizures.
• Medication Change or Withdrawal: Driving is prohibited during any physician-directed AED dose reduction or medication switch, and for 6 months following the final dose reduction. If a breakthrough seizure occurs due to doctor-supervised reduction, the patient must stop driving for 6 months, provided the previous effective drug regimen is reinstated.

Group 2 Licenses (Buses, Coaches, and Heavy Goods Vehicles / Lorries)

• Single Unprovoked Seizure: Must cease driving for a minimum of 5 years. Relicensing requires formal neurological assessment confirming <2% annual recurrence risk.
• Established Epilepsy: Must cease driving for a minimum of 10 continuous years completely seizure-free without taking any antiepileptic medications during that entire 10-year period.