Epilepsy

Definitions:

• Seizures
  • occasional, sudden, rapid and local discharges of gray matter
• Epilepsy
  • brain disorder characterised by periodic, unpredictable occurrence of seizures

Seizures

• Transient changes of behaviour
  • due to disordered, synchronous  and rhythmic firing at high frequency of groups of neurons from the cerebral cortex
• When seizure activity is initiated at local focus (cortex, hippocampus, thalamus)
  • invades normal brain tissue to involve both parts of the cerebral hemispheres
  • a generalised convulsion/seizure occur
• Can be preceded by an aura
  • tingling
  • numbness of limbs
  • hallucinations
• followed by convulsions
  • involuntary skeletal muscle movements
  • loss of consciousness
• After an attack
  • post-ictal depression
    • patient is confused, drowsy and has headache
• Abnormal electrical activity during and after a seizure can be recorded using electrodes placed on the scalp. Called the electroencephalogram (EEG)
  • it shows characterisitic features for various types of seizures
• Repeated epileptic attacks can cause neuronal death

The symptoms of an epilepsy attack depends on

• the site of the primary abnormal electrical discharges
• the extent of their spread

Range of epilepsy attack severity

• A seizure attack may range from a brief lapse of attention to a full convulsive fit with jerky movements.
• The patient may become unconscious for a short time, have a change in perception and experience odd sensations or behaviours
• Others may exhibit repetitive movements like blinking or twitching

When abnormal activities (seizures) involve the:

• motor cortex
  • convulsions occur
• hypothalamus
  • peripheral autonomic effects occur
• reticular formation of the upper brain stem
  • consciousness is lost

Classification of seizure types

Generalised seizures
Seizure activity affect both brain hemispheres

• Generalized tonic-clonic (grand mal) seizures
  • loss of consciousness
  • tonic muscle contractions
  • alternating with clonic contractions (lasting 1-2 minutes)
• Absence (petit mal) seizures
  • abrupt onset of impaired consciousness
    • with staring
  • cessation of ongoing activity
    • lasting less than 3 seconds
  • resumption of activity on end of seizure
    • with no awareness of seizure episode
  • 3 Hz spike EEG. related to:
    • Voltage regulated Ca 2+ current / low threshold
      current (T-current)
• Tonic seizures
• Atonic seizures
• Clonic seizures
• Myoclonic seizures
  • short ( 1 sec) shock-like contraction of muscle
  • may be limited to 1 extremity/generalised

Partial (focal) seizures
seizure activity begins at a focal site in the cortex

• Simple partial seizures
  • Manifestations depend on the region of cortex activated by the seizure:
    • Motor cortex
      • clonic jerking of left thumb
    • Sensory (somatosensory) cortex
      • paresthesia of left thumb
  • Consciousness retained
• Complex partial seizures
  • Loss of consciousness lasting 30sec – 2 min
  • Associated with purposeless movements
    • like lip smacking or hand wringing
• Partial seizures secondarily generalised (tonic-clonic)
  • seizure affecting both brain hemispheres
  • loss of consciousness
  • tonic muscle contractions
    • alternating with clonic contractions
  • lasting 1-2 minutes
• Psychomotor epilepsy
  • Focus on temporal lobe
  • Stereotype
    • purposive movement
      • rubbing/patting movement
    • behaviour
      • dressing, walking, combing hair
  • Could have strong emotional response
  • Seizure lasts few minutes
    • no awareness of event on recovery
• Jacksonian Epilepsy
  • focus of abnormal activity in the motor cortex
  • Repetitive jerking of particular muscle group
    • beginning on 1 side of body
    • Thumb / big toe / angle of the mouth spreading to
      involve other parts of the body within 2 min before
      dying out
  • Voluntary control of the affected parts are lost, but consciousness could be retained

Other types of seizures

• Infantile spasms
• Febrile seizures
• Status epilepticus
  • continous seizure episodes
  • life threatening

Implication of knowing types of seizure

• Importance
  • predicting prognosis
  • selecting treatment
  • likelihood of finding underlying cause of seizure
• 3 stages to a seizure
  • initiation
  • synchronization of surrounding
  • propagation
    • recruitment of normal neurons

Cause of epilepsy

• no recognisable cause
• Develop from brain damage
  • trauma
  • infection
  • tumour growth
  • neurological diseases

Seizure provoking factors

• Missed medication
• Sleep deprivation
• Stress
• Alcohol & Drug abuse
• Over the counter medication
• Nutritional deficiencies:
  • Vitamins and minerals
• The menstrual cycle
• Cycles of the moon
• Bright / flickering light
• Certain sound

Diagnosis of seizures

• Patient history
• Physical examination
• EEG
  • Read from OLIS
• Imaging to localise seizure focus
  • CT scan
  • PET
  • MRI

EEG

• Electroencephalography (EEG) is a test by which the electrical activity generated by the brain is recorded through thin wires placed on the scalp.
  • Normal brain rhythms and any abnormal epileptic activity are reviewed on a computer screen or on paper.
  • The EEG recording assists in determination of the seizure
    type and epilepsy syndrome.
• In special circumstances, EEG may assist monitoring of treatment and help localise the seizure focus.
• EEG should be recorded and interpreted in a centre experienced in management of epilepsies and EEG

Main roles of EEG

• Help distinguish focal from generalised seizures and epilepsies
• Help localise the site of seizure activity in a child with focal epilepsy
• Help make a specific (syndrome) diagnosis
• Help confirm or exclude epilepsy, following a thorough clinical evaluation
• Monitor treatment in some types of epilepsy

Brain imaging

• Structural imaging (CT, MRI)
  • exclude an underlying brain abnormality
    • scar
    • malformation
    • tumour
    • infection
• Functional imagine (SPECT, PET, fMRI)
  • assist localisation of a seizure focus and its relationship to important brain region
  • usually in children considered for brain surgery

Epilepsy – Impact on patients

• The young
  • interruption in their studies, activities, family, career
• Female patients
  • antiseizure drugs on fetal development
    • birth defects (spina bifida, cleft lip etc)
  • antiseizure drugs cause liver enzyme induction
    • failure of oral contraceptives
  • increase risk of bone disease
  • seizures may disrupt functions of estrogen
    • decrease birth rate
    • weight gain
    • abnormal menstrual cycle
    • cyst in ovaries

Neurochemical basis of seizures

• Seizures associated with
  • (-) inhibitory synaptic function (GABA)
  • (+)excitatory synaptic function (Glutamate)
  • Abnormal electrical properties of affected neurons
• seizures in experimental animals caused by:
  • GABAa- antagonists (bicuculline, picrotoxin)
  • Agonists of glutamate receptor subtypes (NMDA, AMPA,
    kainic acid)
• seizures in expt animals alleviated (relieved) by:
  • GABAa- agonists
  • Antagonists of glutamate receptor subtypes (NMDA, AMPA, kinic acid)
• Post-mortem human brains:
  • (-) glutamate in cells of focus
  • (+) in cells surrounding focus

Antiseizure drugs

• Prolong sodium channel inactivation
  • phenytoin
  • carbamazepine
  • lamotrigine
  • phenobarbitone
  • sodium valproate
  • topiramate
  • [-] rapid repetitive firing in isolated neurons
• Reduction of low threshold T-type Ca++ current which govern oscillatory responses in thalamic neurons
  • ethosuximide
• Enhance GABAA activity to inhibit synaptic transmission:
  • Direct action on GABA receptor-chloride
    channel complex
    • benzodiazepines
    • barbiturates
    • topiramate
  • Block reuptake or metabolism of GABA
    • sod valproate
    • gabapentine
    • tiagabine
    • vigabatrin
• Reduce Glutamate transmission:
  • Block of AMPA receptors
    • phenobarbitone
    • topiramate