Epilepsy

Definition/diagnostic criteria

Epilepsy is a neurological condition characterized by recurrent, unprovoked seizures. According to the International League Against Epilepsy (ILAE), a diagnosis can be made in the following situations:

1. Two unprovoked seizures occurring more than 24 hours apart.
2. A single unprovoked seizure with a high recurrence risk (e.g., based on imaging, EEG findings, or clinical context).
3. A diagnosis of an epilepsy syndrome based on clinical and diagnostic features.

Epidemiology

In the UK, epilepsy affects approximately 600,000 individuals (about 1% of the population), making it one of the most common chronic neurological disorders. The condition can begin at any age, but it shows a bimodal distribution, with the highest incidence in childhood and in individuals over 60 years of age. The latter reflects risk factors such as stroke, neurodegeneration, and other age-related pathologies.

Diagnosis

Clinical features

The clinical presentation of epilepsy depends on the type of seizures. Seizures are broadly classified into focal, generalized, and unknown onset, with further subdivisions based on awareness and motor or non-motor symptoms. Key seizure types are described below:

1. Focal Seizures:
   • Originate in a specific region of the brain and may remain localized or spread.
   • Focal aware seizures: Awareness is preserved, and the person remains conscious. Symptoms are highly variable and depend on the brain region involved. For example:
     • Motor symptoms: Twitching or jerking of a limb (Jacksonian march if spreading).
     • Sensory symptoms: Tingling, visual/auditory hallucinations, or olfactory auras (e.g., a burning smell).
   • Focal impaired awareness seizures: Consciousness is impaired, often presenting with automatisms (e.g., lip-smacking, fumbling). Patients may appear “absent” or confused during the episode.
   • Focal seizures may progress to bilateral tonic-clonic seizures (secondary generalization).
2. Generalised Seizures:
   • Originate bilaterally and involve both hemispheres from onset. Awareness is typically impaired. Subtypes include:
     • Tonic-clonic seizures: Previously termed “grand mal seizures,” these involve two phases:
       • Tonic phase: Sudden stiffening of the body, often with vocalization.
       • Clonic phase: Rhythmic jerking of the limbs.
         Postictal confusion, drowsiness, and headache are common.
     • Absence seizures: Brief lapses in awareness, often in children (previously “petit mal seizures”). They may present as staring spells with subtle blinking or facial twitching and are often unrecognized.
     • Myoclonic seizures: Sudden, brief, shock-like muscle jerks. These are common in juvenile myoclonic epilepsy and are often provoked by sleep deprivation or alcohol.
     • Atonic seizures: Sudden loss of muscle tone, leading to falls (“drop attacks”).
     • Tonic seizures: Sudden sustained muscle contraction without jerking, often causing falls.
3. Unknown Onset Seizures:
   • Seizures where the origin is unclear, typically due to incomplete history or lack of witness accounts. These may later be reclassified after further investigations.

The clinical history is critical for diagnosis, and witness accounts are often essential. Key points include the nature of the onset (e.g., aura or warning signs), seizure semiology, duration, frequency, and postictal symptoms.

Investigations

Investigations aim to confirm the diagnosis, classify the seizure type, and identify an underlying cause. A systematic approach includes:

1. Electroencephalography (EEG):
   • EEG is the cornerstone of epilepsy diagnosis and can identify characteristic abnormalities such as focal or generalized epileptiform discharges.
   • Specific patterns may suggest epilepsy syndromes, e.g., 3-Hz spike-and-wave discharges in absence epilepsy or polyspike-and-wave in juvenile myoclonic epilepsy.
2. Neuroimaging (MRI preferred):
   • MRI is recommended to identify structural causes such as cortical malformations, tumors, stroke, or hippocampal sclerosis.
   • CT is a less sensitive alternative and may be used in urgent settings.
3. Other Tests (as indicated):
   • Blood tests: To rule out metabolic or infectious causes.
   • Genetic testing: May be appropriate for epilepsy syndromes with suspected genetic aetiology.
   • Lumbar puncture: Performed if there is a suspicion of CNS infection or inflammation.
   • Cardiac evaluation: ECG and ambulatory monitoring are indicated if a cardiac cause (e.g., syncope or arrhythmia) is considered.

Treatment

General principles

The primary aim of epilepsy treatment is seizure control with minimal side effects. Treatment choice depends on the type of seizures, epilepsy syndrome, comorbidities, and patient-specific factors such as age, sex, and concomitant medications.

First-Line Antiepileptic Drugs (AEDs)

1. Focal Seizures:
   • Carbamazepine and lamotrigine are commonly used first-line options.
   • Levetiracetam or sodium valproate may also be used, depending on individual factors such as side effect profiles and comorbidities.
   • Carbamazepine is effective but requires monitoring for side effects like hyponatremia and rash. Lamotrigine is better tolerated but must be titrated slowly to avoid rash.
2. Generalized Seizures:
   • Sodium valproate is highly effective for generalized tonic-clonic, absence, and myoclonic seizures. However, due to the risk of teratogenicity, UK guidelines state it should not be initiated in females of childbearing potential unless no other effective treatment exists and with strict precautions.
   • Alternatives include lamotrigine (effective for generalized tonic-clonic seizures but less so for myoclonic or absence seizures) and levetiracetam.
3. Specific Seizure Types:
   • Absence seizures: First-line treatment is ethosuximide or sodium valproate.
   • Myoclonic seizures: Sodium valproate is the drug of choice; alternatives include levetiracetam.
   • Atonic seizures: Sodium valproate or lamotrigine may be used, but seizure control can be challenging.

Refractory Epilepsy

Around 30% of patients have drug-resistant epilepsy, requiring additional interventions:

• Surgical evaluation: For patients with resectable focal epilepsy, surgery (e.g., temporal lobectomy) may achieve seizure freedom.
• Vagus nerve stimulation (VNS): An option for patients unsuitable for surgery.
• Ketogenic diet: Particularly useful in pediatric refractory epilepsy (e.g., Dravet syndrome).

Prognosis

The prognosis of epilepsy is highly variable and depends on factors such as the underlying cause, seizure type, and response to treatment. Approximately 70% of individuals achieve seizure freedom with appropriate AED therapy. However, comorbidities such as depression, anxiety, and cognitive impairments are common and may impact quality of life.

Sudden Unexpected Death in Epilepsy (SUDEP):

SUDEP is a significant concern, particularly in patients with uncontrolled generalized tonic-clonic seizures. Risk factors include nocturnal seizures, frequent seizures, and poor medication adherence. Educating patients and optimizing seizure control can reduce SUDEP risk.