Epilepsy

Epilepsy is a primary seizure disorder with recurrent (⩾2) epileptic seizures.

This covers epilepsy. Management of seizures including status epilepticus are covered at Seizures, and NCSE is covered at Non-Convulsive Status Epilepticus.

Epidemiology and Risk Factors

Prevalence:

  • Most common serious neurological disorder
  • ~0.5-1% of the population

Incidence:

  • Bimodal
    • Extremes of age

Risk factors:

  • Male
  • Lower socioeconomic status
  • Brain abnormality
    • Structural
    • Developmental

Pathophysiology

Aetiology

Multiple causes exist, and include:

  • D
    • Migraine
    • Cerebrovascular disease
      • CVA
        Equally likely after infarction or haemorrhage.
    • Tumour
      • Anterior
      • Slow-growing
    • Degenerative
      • Dementia
      • Alzheimer’s Disease
    • Post-syncope
  • F
    • Hypo/hypernatraemia
    • Hypo/hypercalcaemia
    • Hypo/hypermagnesaemia
    • Hypoglycaemia
  • Immune
    • Multiple sclerosis
  • Traumatic
    Post-traumatic epilepsy associated with:
    • Early seizures
    • Depressed skull fractures
    • ICH
  • Infective
    • Meningitis
    • Encephalitis
  • Congenital
    • Associated with other disorders
      • Down’s Syndrome
      • Mitochondrial disease
    • Epilepsy syndromes
      • Juvenile myoclonic epilepsy
      • Benign rolandic epilepsy

Clinical Manifestations

History

Examination

Diagnostic Approach and DDx

Investigations

Bedside:

  • BSL

Laboratory:

  • UEC
  • CMP
  • Prolactin

Imaging:

  • CTB
    Evaluation of structural cause.
  • MRI
    Evaluation of structural cause, with ↑ sensitivity and specificity compared with CT.

Other:

  • EEG:
    • Interpretation may be difficult
    • Patients with disease will have abnormalities ~50% of the time

Management

  • Single-agent therapy optimised before progressing to multi-agent therapy
    • If adverse effect to first agent, a second agent tried as monotherapy
    • If seizures continue despite adequate dosing, combination therapy usually begun
  • Significant side effect profile of many older agents
  • Usually continued until 2-3 year seizure-free period
    • Drugs may then be withdrawn over 3-6 months
    • ~66% of patients will remain seizure free
  • Drug therapy depends on type of epilepsy
  • Patients who have had one episode of status epilepticus should be prescribed benzodiazepines to treat refractory status

Management of active seizures is covered under Seizures.

Specific therapy:

::: Antiepileptics have extensive drug interactions, predominantly related to CYP450 induction and inhibition:

  • Inductors

    • Carbamazepine
    • Phenytoin
    • Phenobarbital
    • Primidone

  • Inhibitors :::

  • Pharmacological

    • Focal seizures
      • Lamotrigine
      • Carbamazepine
    • Generalised
      • Valproate
        Most effective drug for primary generalised epilepsy.

  • Procedural

  • Physical

Mechanisms of Action
Mechanism Drug
↑ GABA Cl- channel opening frequency
  • Benzodiazepines
  • Tiagabine
  • Gabapentin
↑ GABA Cl- channel opening duration
  • Barbiturates
Block GABA transaminase Vigabatrin
Antagonise glutamate Topiramate
↓ Inward voltage-gated positive currents
  • Phenytoin
  • Carbamazepine
  • Ethosuximide
↑ Outward voltage-gated positive currents
  • Valproate
Pleotropic
  • Valproate
  • Lamotrigine
  • Topiramate

Anaesthetic Considerations

  • D
    • Anaesthetic affects
      Drugs may:
      • Modulate seizure activity
        Can be:
        • Pro-convulsant
        • Anti-convulsant
        • Both
      • Interact with antiepileptic medication
    • General principles
      • Continue antiepileptic drugs on day of surgery, and recommence as soon as possible afterwards
        Administer parenterally if multiple doses missed or are likely to be missed.
      • Avoid epileptogenic drugs
      • Note presence of drug interactions
Effect of Anaesthetic Agents on Epilepsy
Agent Effect
Nitrous Oxide Seizures in mice, but not in humans
Sevoflurane

May induce seizure-like activity particularly:

  • In children
  • With associated hypocapnoea
Isoflurane Antiepileptic, may be used in refractory status epilepticus
Desflurane Antiepileptic
Opioids Lower seizure threshold, and may be used to potentiate seizures
Barbiturates Antiepileptic, may be used in status
Propofol Antiepileptic, may be used in status
Ketamine ↑ Seizures at low dose, ↓ seizures at anaesthetic doses
NMBD No effect

Marginal and Ineffective Therapies

Complications

Pregnancy:

  • 4-8% risk of congenital malformations
  • ↑ seizure frequency in ~30% of patients
  • GTCS associated with ↑ miscarriage risk
  • Excretion of benzodiazepines and barbiturates in baby

Prognosis

Related to severity and degree of control. Morbidity associated with:

  • Requiring ⩾3 antiepileptic drugs
  • Status epilepticus

Key Studies

References

  1. Gratrix AP, Enright SM. Epilepsy in anaesthesia and intensive care. Continuing Education in Anaesthesia Critical Care & Pain. 2005 Aug;5(4):118–21.
  2. Perks A, Cheema S, Mohanraj R. Anaesthesia and epilepsy. Br J Anaesth. 2012 Apr 1;108(4):562–71.