Epilepsy

• What is epilepsy ?

  It is a chronic neurological disroder, characterized by excessive, repetetive, spontaneous abnormal electrical discharges. These are due to the activation of large nb of neurons.
• What are the 2 patterns of epilepsy ?

  Ictal or Interictal
• How to define ictal activity ?

  • long
  • low frequency
  • have tonic and clonic electrical activity
• How to define interictal ?

  • short
  • high frequency
  • have spikes due to paroxysmal depolarization
• What is paroxysmal depolarization ?

  Sudden prolonged depolarization during which multiple AP can occur involving the calcium current. ONly the activation of potassium channel can stop PDS
• What is tonic activity ?

  • low voltage
  • fast activity increasing with amplitude
• What i clonic activity ?

  Burst of rhythmic waves of depolarization and high amplitudes
• What are are 2 ways to classify epilepsy ?

  • Phenotype
  • Cause
• What are the phenotypic classification of epilepsy ?

  • Partial seizure : with simple vs complex
  • Generalized seizure
• What does the partial complex seizure involve that the simple one does not ?

  The loss of consiousness
• What are the possible causes classification of epilepsy ?

  • Channelopathies = biophysical changes
  • Morphological changes
• What are the 3 possible biophysical changes observed in epilepsy ?

  • Mutation of sodium channels
  • Change of GABA transmission and chloride current
  • Calcium channels
• What things GEFS+ has that SMEI does not ?

  It has increase of body temperature and no cognitive deficits
• What are the 2 pathologies due to biophysical changes ?

  • GEFS +
  • SMEI
• What are the possible sodic mutation ?

  • SCN1A
  • SCN1B
• What is the result of SCN1A vs SCN1B ?

  • SCN1A : gain or loss of function
  • SCN1B : reduced dendritic arborization
• What are the 3 theories about SCN1A mutation ?

  • Gain of function = persistent sodic channel like in GEFS +
  • Loss of function = in interneurons OR residual sodic compensation
• What are the 2 possibilites for the loss of function and in which case they happen ?

  • Loss in interneurons = no inhibition = increase excitability of network
  • Loss = residual compensation by other channels = increase sodium current
• If I have a gain of function of Nav1.1 which epilepsy am I : GEFS or SMEI ?

  GEFS
• If I have a loss of function of Nav1.1 which epilepsy am I : GEFS or SMEI ?

  SMEI
• What type of SCN1B mutation can be found in GEFS vs SMEI ?

  • GEFS is a heterozygous mutation
  • SMEI is a homozygous
• What happens if GABA transmission is mutated ?

  • Reduced KCC2 expression
  • Movement of chloride potential to more positive values
  • Reduces inhibitory action of GABA
  • Increase excitability
• Which channel favors burst activity ?

  T type calcium channels
• What are thalamocortical dysfunctions similar to ?

  Sleep spindles
• What are the differences between sleep spindes and absence epilepsy ?

  • Sleep : small amplitude, high frequency, no need for cortex
  • Epilepsy : big amplitude, low frequency, need for cortex
• What happens in TC cells in order to produce spike wave discharge ?

  T type calcic channels are very active which increase bursts
• What happens between RTN and TC in case of abnormal channel function ?

  Increase of inhibitory transmission
• How to obtain low frequency in epilepsy compaired to sleep ?

  Due to increase of inhibitory transmission period from RTN to TC
• What elements cause amplitude and frequency changes in epliepsy compared to sleep ?

  • amplitude : T calcium channels and GABA A
  • frequency : GABA B
• What causes GABA B in the RTN and TC transmission ?

  1. GABA B increases duration of hyperopolarization
  2. Elongation of inhibitory period
  3. Decrease of oscillation frequency aka longer hyperpol
• What causes GABA A in the RTN and TC transmission ?

  1. GABA A : increased hyperpolarization produces inhibiton
  2. Recovery of T calcium channels
  3. Increase neurons with brust activity
  4. Increase amplitude of cortical oscillations
• In which case is cortical activation necessary : sleep spindles or spike wave discharge of epilepsy ?

  Spike wave discharge
• What happens if there is cortical activation ?

  Activates the RTN neurons which increases inhibition of RTN on TC therefore increase amplitude + decrease frequency
• What morphological alteration of NET you have n epilepsy ?

  • Cortical dysplasia
  • Traumas
• What causes temporal lobe epilepsy ?

  • loss of neurons in CA1 and CA3 of hippocampus but not everywhere : selective loss of neuronal population
  • formation of reccurent aberrant excitatory connections = axonal sprouting
• What are the 3 phases of epilepsy ?

  • Triggering events
  • Latent period
  • Epilepsy maniesfation
• Which epilepsy acquisition phase is refered to in epileptogenesis ?

  Latent period