Epilepsy

Question 1

What is epilepsy?

Answer 1

• neurological disorder characterised byrecurrent seizures
• Epilepsy is an umbrella term for a condition where there is a tendency to have seizures.

Question 2

What are seizures?

Answer 2

• Aseizure is defined as aparoxysmal alteration ofneurological function as a result of excessive,hypersynchronous discharge of neurons within the brain.
• For a diagnosis of epilepsy, seizures should beunprovoked and not as a response to a reversible insult such as afever,hypoglycaemia or alcohol withdrawal
• Seizures are transient episodes of abnormal electrical activity in the brain.
• There are many different types of seizures.

Question 3

What is the epidemiology of epilepsy?

Answer 3

• common neurological disorder that affects > 50 million people globally.
• The prevalence of epilepsy in theUK is estimated to be5-10 cases per 1000 people.
• The lifetime risk of having a seizure is approximately 1 in 10.
• Incidence is age-dependent, it is highest at the extremes of life with most cases starting before 20yrs or after the age of 60yrs

Question 4

What are the inherited risk factors of epilepsy?

Answer 4

Inherited, acquired and mixed:

Inherited

• Premature birth
• Congenital malformations of the brain
  
  • Brain development malformations
• Genetics conditions associated with epilepsy
  
  • Cerebral palsy: up to 30% have epilepsy
  • Tuberous sclerosis
  • Neurofibromatosis
  • Metabolic disorders:e.g. lysosomal storage disorders
  • Mitochondrial diseases:e.g. MELAS
• Family history: epilepsy orneurological illness
• Arterio-venous malformations

Question 5

What are the acquired risk factors of epilepsy?

Answer 5

Acquired

• Febrile convulsions as a child: particularly if complex
• Head trauma ⇒ Traumatic brain injury
• Neurodegenerative disease
• Ischaemic stroke
• Brain tumour
• Cerebral infections
  
  • Intracerebral infection:meningitis,encephalitis, abscess
• Cerebrovascular disease

Question 6

What are the mixed risk factors of epilepsy?

Answer 6

Mixed

• Dementia:10x more likely to develop epilepsy in Alzheimer’s disease

Epileptic patients can have theirthresholdfor having a seizureloweredby certaintriggers:

• Non-adherence with anti-epileptic drugs (AEDs)
• Fatigue
• Stress
• Alcohol or recreational drugs
• Flashing lights
• Hypoglycaemia
• Febrile illness
• Medication: CYP450 inhibitors/inducers, e.g. ciprofloxacin (CYP1A2 inhibitor) can lower seizure threshold

Question 7

What is the pathophysiology of epilepsy?

Answer 7

The disrupted neurological function causing a seizure is the result of animbalance betweenexcitation and inhibition within theneurons of thebrain. The pathogenesis of this distortion is poorly understood but can be bothgeneticandacquired.

A seizure is a period where neurones in the brain are synchronously active - active at the same time, when they’re not supposed to be.

Question 8

What are the causes of epilepsy?

Answer 8

The cause of epilepsy can be broadly divided into six groups:

• Genetic: known or presumed genetic mutation that predisposes torecurrent seizures.Some patients with epilepsy seem to have fast or long-lasting activation of excitatory NMDA receptors and some patientsseem to have genetic mutations in which their inhibitory GABA receptors are dysfunctional.
• Structural: visible neurological abnormalities that predisposeto seizures (e.g. chronic cerebrovascular disease, congenital malformation)
• Metabolic: known or presumed metabolic disorder that predisposes to seizures
• Immune: underlying immune disorder that predisposes to recurrent seizures
• Infectious: chronic infection predisposingto seizures (e.g. HIV). This must bedifferentiated from seizures associated with an acute infection (e.g. meningitis)
• Unknown: up to one third of patients.

Question 9

What are seizures like?

Answer 9

During a seizure, a clusters of neurones in the brain become temporarily impaired and start sending out a ton of excitatory signals - these are sometimes said to be paroxysmal. These paroxysmal electrical discharges are thought to happen due to either too much excitation, or too little inhibition.

Whether it’s a decrease in inhibition or an increase in activation, when groups of neurones start firing simultaneously, it’s often noticed by others as obvious outward signs, like jerking, moving, and losing consciousness, but can also be subjective experiences that are only noticed by the person experiencing it, like fears or strange smells but can also involve jerking movements in specific muscle groups if the neurones controlling those muscles are affected.

If the jerking activity starts in a specific muscle group, and spreads to surrounding muscle groups as more neurons are affected, it’s referred to as a Jacksonian march.