Epilepsy

• What are the causes of epilepsy?

  Unknown in 50% of cases

  all types of epilepsy thought to be genetic on some level

  can be caused by stroke or brain tumours - note excess excitation and reduced inhibition both can cause seizures
• what are generalised seizures and what are the types?

  Generalized seizures involve abnormal electrical activity throughout the brain. Types include tonic-clonic, absence, myoclonic, atonic, and tonic seizures.
• describe tonic clonic seizures

  also known as motor seizures

  sudden loss of consciousness followed by a tonic phase (contraction fo muscles) and a clonic phase (shaking of extremities)

  incontinence, eyes roll back and tongue biting

  can happen with aura, post-seizure amnesia, abnormal neuroimaging
• describe absence seizures

  also known as non-motor seizures

  very brief attakcs

  characterised by sudden interruption of onghoging activity which is resumed once the seizure is over

  normal neuroimaging

  can get automatisms

  not noticed by patients
• what are focal seizures and what are their types?

  Focal seizures are seizures that originate in one area of the brain. Types include focal aware seizures (previously called simple partial seizures) and focal impaired awareness seizures (previously called complex partial seizures).
• describe focal onset aware seizures

  consciousness is always intact

  can be motor or sensory depending on the focus
• describe focal onset impaired awareness

  disturbed unconsciousness

  associated with temporal lobe lesions

  confusion/amnesia after the episode

  automatisms - fumbling with clothes or licking lips uncontrollably
• what are generally the first line treatments for epilepsy and what are their requirements?

  1= sodium valproate - males and kids under 10 or women that can’t have kids

  2= lamotrigine - monitor for signs of rash - hypersensitivity syndrome

  3 = levetiracitam - many side effects which are problems with larger doses - suicidal intent

  4= carbamazepine - many interactions - strong CYP inducer, can exacerbate myoclonic and absence seizures

  5= phenytoin - narrow therapeutic index and acute toxicity - plasma drug concentration not linear - needs to be monitored to ensure optimal dose - not really used
• what is teh importance of BZD’s in epilepsy?

  they aren’t really used for maintenace therapy due to sedative effects and tolerance over time
• how should epilepsy be managed?

  monotherapy if possible - fewer side effects

  if this fails then MDT - no more than 3 AEDs

  if not controlled after 3 consider surgery
• describe the MOA of AEDs

  decrease excitatory mechanisms by inhibiting sodium and calcium channels and increasing GABA funciton

  aim is to reduce frequency and severity of attacks

  note with the GABA that preventing peripheral breakdown increases the amount in neurons which therefore prevents seizures
• how does blocking sodium channels help to treat epilepsy

  blocking sodium channels block the action of repetitively firing cells - this blocks high frequency discharge that occurs in epileptic attemps because they are use dependent
• how does blocking calcium channels help to treat epilepsy?

  T-type channels are importanty in teh rhythmic discharge of thalamic neurons in absence seizures

  gabapentin and pregablin act on P/Q type calcium channels to reduce calcium entry into nerve terminals
• What is the importance of AMPA receptor inhibition?

  Perampanel inhibits AMPA induced increases in calcium by selectively blocking AMPA receptor mediated synaptic transmission therefore reducing excitation
• importance of SV2A receptor inhibition in epilepsy

  inhibition of SV2A reduces the release of glutamate which reduces calcium influx and therefore prevents excitation and seizures

  drugs include levetiracetam and biveracetam
• which AEDs should NOT be used in pregancy and why?

  sodium valproate, topiramate, carbamazepine and oxcarbamazepine

  they are TERATOGENIC

  these all induce CYP3A4 enzymes therefore effective contraception is required
• what happens if a woman becomes pregant while taking AEDs?

  consultation with specialist required to see if teh medication needs to be changed or if it is safe to continue

  folic acid high dose supplements to be started - can help to avoid some of teh teeratogenic effects of some medications
• what happens if a woman accidentally becomes pregnant while on AEDs?

  do not stop taking the AEDs without advice from a specialist first

  start on lowest dose possible via monotherapy and start high dose folic acid supplements
• what needs to happen once a baby is born with a mother who takes AEDs?

  newborns can have withdrawal effects from some AEDs as they can cross the placenta
• describe the different categories of AEDs and give examples

  1 = clinically relevant difference between products, specific manunfacturers products - should not switch between these - carbamazepine

  2 = anything not in 1/3 - base need on continued supply on specific manufacturer on clinical judgement - lamotrigine

  3= no issues in switching between manufacturers - levetiracetam
• how and when should AEDs be withdrawn?

  patient must be seizure free for minimal 2 years

  do assessment of risk for recurrence

  gradual dose reduction - should take roughly 3 months

  could lose driving license if having a seizure while driving