CNS (Seizure)

• Seizure


  The clinical manifestation of an abnormal and excessive excitation and synchronization of a population of cortical neurons
• Epilepsy


  A disease characterized by spontaneous recurrent seizures
• Convulsion


  Contractions of large group of muscles
• Cellular Mechanisms of Seizure Generation

  • Excitation (too much): Ionic—inward Na+, Ca++ currents; Neurotransmitter—glutamate, aspartate
  • Inhibition (too little): Ionic— inward Cl-, outward K+ currents; Neurotransmitter— GABA
• Causes of Seizures


  • CHILDREN: idiopathic, birth and neonatal injuries, vascular lesions (AVM, aneurysm), congenital or metabolic disorders, head injuries, infections, neoplasia, heredity
  • ADULT: idiopathic, vascular lesions, head trauma, neoplasia, infection, metabolic, heredity
• Types of Seizure


  • PARTIAL/FOCAL
  • GENERALIZED
• Partial/Focal Seizures


  • Simple partial seizures
  • Complex partial seizures
  • Partial seizure with secondary generalization
• Simple Partial Seizure


  Focal with minimal spread of abnormal discharge, normal consciousness and awareness are maintained
• Complex Partial Seizure


  Local onset, then spreads, impaired consciousness, involves the limbic system, presents with automatisms (lip smacking, scratching); arises from temporal lobes
• Generalized Seizures


  Both hemispheres are widely involved from the outset, manifestations of the seizure are determined by the cortical site at which the seizure arises
• Generalized Seizures


  • Tonic-clonic
  • Absence seizure
  • Tonic Seizure
  • Myoclonic Seizure
• Tonic-Clonic Seizure


  Major convulsions with rigidity (tonic) and jerking (clonic), slows over 60-120 sec followed by stuporous state (post-ictal depression)
• Absence Seizure


  Sudden onset and abrupt cessation, brief duration, consciousness is altered, attack may be associated with mild clonic jerking of the eyelids or extremities, postural tone changes, autonomic phenomena and automatisms, characteristic 2.5-3.5 Hz spike-wave pattern
• Tonic Seizure


  Spasm of the muscles causing backward arching of the head, neck, and spine
• Myoclonic Seizure


  Myoclonic jerking is seen in a wide variety of seizures but when this is the major seizure type it is treated differently to some extent from partial leading to generalized
• Classical Anticonvulsants


  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Valproic Acid
  • Ethosuximide
• Newer Anticonvulsant Agents


  • Gabapentin, Pregabalin
  • Tiagabine
  • Vigabatrin
  • Lamotrigine
  • Levetiracetam
  • Topiramate
• Phenytoin


  For partial seizures, known for decades as diphenylhydantoins, oldest non-sedative AED, mechanism of action is blocking Na channels (major action)
• Phenytoin Side Effects


  • Nystagmus
  • Diplopia
  • Gingival Hyperplasia
  • Hirsutism
  • Fetal Hydantoin Syndrome
  • Enzyme Inducer
• Carbamazepine


  Mechanism of action is enhancing GABA receptor mediated current by prolonging opening of chloride channels and blocks excitatory responses induced by glutamate, clinical use is for partial and generalized tonic-clonic seizures (not for absence, atonic and infantile spasms)
• Phenobarbital


  Mechanism of action is inhibiting Na channels, it has inhibitory effect on the GABA transporter GAT-1 and GABA transaminase (thus blocking GABA degradation), increases GABA
• Valproic Acid


  Mechanism of action is blocking Ca2+ currents in the thalamus, drug of choice for absence seizure/petit mal, side effects include hepatoxicity, enzyme inhibitor, neural tube defects
• Ethosuximide


  Mechanism of action is blocking Ca2+ currents in the thalamus, drug of choice for absence seizure/petit mal
• Gabapentin and Pregabalin


  Clinical use is for partial and generalized tonic-clonic seizures but very high dosage is required, also good for neuropathic pain, side effects include somnolence, dizziness, ataxia, headache and tremor
• Tiagabine


  Mechanism of action is inhibitor of GABA reuptake, increasing levels of GABA, clinical use is as adjunctive treatment of partial seizure
• Vigabatrin


  Mechanism of action is irreversible inhibitor of GABA aminotransferase (GABA-T), the enzyme responsible for degradation of GABA, clinical use is for partial seizures and WEST syndrome
• West Syndrome


  Severe epilepsy syndrome composed of the triad of infantile spasms, an interictal electroencephalogram (EEG) pattern termed hypoarrhythmia, and mental retardation
• Lamotrigine


  Mechanism of action is blocking Na and Ca currents, decreasing glutamate, used for seizures in pregnancy and Lennox Gestaut syndrome, adverse reactions include dizziness, headache, diplopia, nausea, somnolence and skin rash, life threatening dermatitis (SJS) can occur
• Levetiracetam


  Mechanism of action is binding selectively to synaptic vesicular protein SV2A, modifying release of GABA and glutamate, clinical use is for partial seizure and myoclonic seizures, side effects include somnolence, psychosis, dizziness
• Topiramate


  Mechanism of action is blocking Na, Ca, Glutamate, increasing GABA, used for childhood epilepsy syndrome, side effects include urolithiasis
• Use of Anticonvulsants


  • Status epilepticus (> 30 mins): Diazepam/Lorazepam, Phenobarbital, Phenytoin, Valproic Acid, Midazolam, other barbiturates
  • Seizures in pregnancy (Eclampsia): Generalized tonic clonic seizure, Magnesium Sulfate, Fetal neuroprotection, prolonged pregnancy up to 48 hrs