Key Facts

Epilepsy is one of the most common serious neurological conditions. Accurate seizure classification is essential as treatment differs by seizure type. Most patients (60-70%) achieve seizure freedom with appropriate medication.

Epidemiology

Prevalence ~1% in UK (~600,000 people). Incidence ~50 per 100,000 per year. Bimodal age distribution: peak in first year of life and >65 years. 25% of new diagnoses are in elderly. Lifetime risk ~3%. Accounts for ~1,000 deaths/year in UK (including ~500 SUDEP).

Aetiology

• Structural: hippocampal sclerosis (mesial temporal lobe epilepsy), cortical dysplasia, tumour, vascular malformation, previous stroke/TBI
• Genetic: idiopathic generalised epilepsies (juvenile myoclonic epilepsy, childhood absence epilepsy), SCN1A (Dravet syndrome)
• Infectious: post-meningitis/encephalitis, neurocysticercosis
• Metabolic: mitochondrial disorders, pyridoxine-dependent epilepsy
• Immune: autoimmune encephalitis (NMDA-R, LGI1, CASPR2)
• Unknown: ~50% of cases have no identified cause

Pathophysiology

Seizures result from abnormal, excessive, synchronous neuronal discharge. This may arise from an imbalance between excitatory (glutamate) and inhibitory (GABA) neurotransmission. Focal seizures originate from a localised network; generalised seizures involve widespread bilateral networks from onset. Epileptogenesis is the process by which a normal brain becomes epileptic (e.g., after head injury, stroke) — involves neuronal reorganisation, gliosis, and altered channel/receptor expression.

Focal Seizures

• Focal aware (previously simple partial): preserved consciousness; motor, sensory, autonomic, or psychic symptoms depending on cortical origin
  • Temporal: déjà vu, rising epigastric sensation, automatisms, emotional changes
  • Frontal: motor (clonic jerking), head/eye turning, vocalisation
  • Parietal: tingling, numbness
  • Occipital: flashing lights, visual hallucinations
• Focal impaired awareness (previously complex partial): impaired consciousness; temporal lobe most common; automatisms (lip-smacking, picking, fumbling)
• Focal to bilateral tonic-clonic: starts focally then generalises

Generalised Seizures

• Tonic-clonic (GTC): sudden LOC, tonic phase (stiffening, fall) → clonic phase (rhythmic jerking) → post-ictal confusion/drowsiness
• Absence: brief (5-15 seconds) staring episodes, unresponsive; no post-ictal state; 3 Hz spike-and-wave on EEG
• Myoclonic: sudden brief jerks; common in JME (typically morning myoclonic jerks)
• Tonic: sudden stiffening (often nocturnal, in Lennox-Gastaut)
• Atonic: sudden loss of tone, drop attacks

Red Flags

• New-onset seizures in adult (exclude structural cause — tumour, stroke)
• Seizures with fever in adult (meningitis/encephalitis)
• Progressive neurological deficit between seizures (space-occupying lesion)
• Status epilepticus (seizure >5 minutes or recurrent without recovery)
• Post-ictal Todd's paresis lasting >24 hours (consider stroke)

First Seizure / Suspected Epilepsy

• EEG: should be performed in ALL suspected epilepsy; interictal epileptiform discharges support diagnosis (but normal EEG does NOT exclude epilepsy — ~50% normal on first recording)
  • Focal spikes/sharp waves → focal epilepsy
  • 3 Hz spike-and-wave → childhood absence epilepsy
  • 4-6 Hz polyspike-and-wave → JME
  • Sleep-deprived EEG increases yield
• MRI brain: all adults with epilepsy (NICE NG217); identify structural cause (hippocampal sclerosis, tumour, cortical dysplasia, vascular malformation)
• ECG: exclude cardiac cause of LOC (long QT, Brugada)

Bloods

• Glucose, calcium, sodium, magnesium: metabolic causes
• FBC, LFTs, U&Es: baseline before starting AEDs
• Prolactin: raised 10-20 minutes after GTC (helps distinguish from PNES; limited specificity)

Special Tests

• Video-EEG telemetry: gold standard for seizure classification and diagnosis of PNES
• Neuropsychology: pre-surgical evaluation
• MRI with epilepsy protocol: thin cuts through hippocampi, FLAIR, volumetric
• PET/SPECT: functional imaging for pre-surgical evaluation (identify seizure focus)

Non-pharmacological

• Lifestyle: regular sleep, avoid alcohol excess, stress management
• Seizure diary: track frequency, type, triggers
• Safety advice: avoid swimming alone, heights, open fires; supervised bathing
• DVLA: must not drive until seizure-free for 12 months (group 1) or 10 years off medication (group 2); must inform DVLA
• First aid for seizures: protect from injury, recovery position after convulsion, do NOT restrain or put anything in mouth, call 999 if seizure >5 minutes

Pharmacological (NICE NG217)

Focal seizures:

• First-line: lamotrigine (titrate slowly: 25 mg OD × 2 weeks → 50 mg OD × 2 weeks → increase by 50-100 mg every 1-2 weeks; usual dose 100-200 mg BD) or levetiracetam (250-500 mg BD, increase to 500-1500 mg BD)
• Second-line: carbamazepine 100-600 mg BD, oxcarbazepine, zonisamide, lacosamide

Generalised tonic-clonic:

• First-line: sodium valproate 300-1000 mg BD (NOT in women of childbearing potential — MHRA) or lamotrigine (if valproate unsuitable)
• Second-line: levetiracetam, topiramate

Absence:

• First-line: ethosuximide 250-500 mg BD or sodium valproate
• Second-line: lamotrigine (less effective for absences)

Juvenile myoclonic epilepsy (JME):

• First-line: sodium valproate (most effective) or levetiracetam (if valproate unsuitable)
• AVOID: carbamazepine, phenytoin, gabapentin (can worsen myoclonic/absence seizures in generalised epilepsy)

Women of childbearing potential:

• Valproate Pregnancy Prevention Programme (MHRA): must use effective contraception; annual risk acknowledgement form
• Preferred: lamotrigine or levetiracetam
• Folic acid 5 mg/day: all women with epilepsy planning pregnancy (start 3 months pre-conception)

Surgical/Interventional

• Epilepsy surgery: consider referral if drug-resistant epilepsy (failed ≥2 appropriate AEDs); temporal lobe resection for mesial temporal sclerosis (60-70% seizure-free); NICE recommends early referral to tertiary epilepsy centre
• Vagus nerve stimulation (VNS): palliative; reduces seizure frequency by ~50% in ~30-40%
• Ketogenic diet: mainly used in children with drug-resistant epilepsy

Referral Criteria

• First seizure: neurology (seen within 2 weeks — NICE NG217)
• Drug-resistant epilepsy (≥2 AED failures): tertiary epilepsy centre
• Women of childbearing potential on valproate: specialist review
• Diagnostic uncertainty: video-EEG telemetry

60-70% of patients achieve seizure freedom with appropriate AED. ~30% have drug-resistant epilepsy. Epilepsy surgery can achieve 60-70% seizure freedom in temporal lobe epilepsy. SUDEP (Sudden Unexpected Death in Epilepsy): ~1 per 1000 patient-years (higher in drug-resistant epilepsy — up to 1 in 150); risk factors: nocturnal seizures, uncontrolled GTC seizures, polytherapy. Overall life expectancy reduced by ~10 years compared to general population (related to underlying aetiology and SUDEP).

AED Selection Summary

SUDEP Risk Factors