CC1 - Epilepsy

Question 0

Seizure Classification

Answer 0

1. Partial (Focal) = Involves only one hemisphere
   
   • Simple Partial = No loss of consciousness (figure of 4s?)
   • Complex Partial = Loss of consciousness
   • -Can become generalized (Secondary Generalized)
2. Generalized = Onset in both hemispheres
   
   • Convulsive
   • Non-convulsive
   • -Are usually cortical, not subcortical, so they spread easily
   • -“epileptic cry” is first sign of generalized tonic seizure

Question 1

Seizure Definitions

Answer 1

• Abnormal excessive and synchronous electrical discharges of brain neural network, leading to paroxysmal events characterized by clinical signs and/or symptoms
• Aura vs Prodrome
  
  • Prodrome = Change in behavior or mood prior to a seizure (Pre-Ictal)
  • Aura = Initial portion of the seizure, including electrical charges (Ictal)
• Ictal = Seizure period/episode or events due to a seizure
• Interictal = Period between two seizures
• Post-Ictal = Events occurring after the end of the seizure

Question 2

Epilepsy

Answer 2

• Disease of the brain characterized by enduring predisposition to generate epileptic seizures
• Classification:
  
  1. Idiopathic - Presumed Genetic Etiology
  2. Symptomatic - Consequence of a known or suspected CNS disorder
  3. Cryptogenic - Unknown cause

Question 3

Epileptic Channelopathies

Answer 3

• Lowered seizure threshold due to mutation causes changes in the current carried by the channel
  
  • Enhanced = gain of function, Reduced = Loss of function
• Usually autosomal dominant and De Novo mutations

1. Severe Myoclonic Epilepsy of Infancy (SMEI)
   
   • 1st year = febrile seizures, progressively prolonged/cluster seizures
   • 2nd year = psychomotor delay, ataxia, cognitive impairment
   • ->Reduction of Na+ channel density causes loss of high-frequency AP, resulting in seizures via loss of GABAergic cortical interneuron inhibitory function, and ataxia via loss of GABAergic Purkinje Cells inhibitory function
   • Treatment = Restablish GABAergic transmission
2. Generalized Epilepsy w/ Febrile Seizures plus (GEFS+)
   
   • Milder than SMEI and with NO cognitive impairment
   • ->Mutation causes loss of function of fast inactivation of Na+ channels! leading to a gain of function of Na+ channels so that there is always a persistent Na+ depolarizing current
3. Febrile Seizures
   
   • Seizure occurring in childhood after 1 month of age and associated with fever not caused by infection of the CNS
   • ->Mutation in Nav1.1 causes reduction of peak Na+ currents so positive shift in voltage dependence of activation
4. Benign Familial Neonatal Convulsion (BFNC)
   
   • Mutation in K+ channel causes loss of function of K+ current
   • Brief generalized and partial seizures that resolve by age 6 weeks