epilepsy

Definition

Seizure : abnormal neural discharge in the cerebral cortex that result in abnormal function, the nature of clinical manifestations depends on the regions of the brain affected.

Epilepsy : Recurrent seizures unrelated to fever or acute cerebral insult.

Epilepsy- questions ?

• 1- seizure?
• 2- seizure-type?
• 3- fits a syndrome?
• 4- identifiable cause?
• 5- anti-epileptic drug (AED)?
• 6- when to stop treatment?
• 7- surgery?

History of events

• Frequency
• Timing
• Duration * Triggers
• Warning
• Color change- pallor, cyanosis
• Alteration in consciousness
• Motor phenomena
• Associated s/s- incontinence, injury
• Symptoms following attack- postictal

Differential diagnosis

• Pseudo seizure- psychiatric
• Syncope- cardiac or neurological
• Movement disorder
• Migraine
• Transient ischemic attack
• Metabolic disorders- hypoglycemia
• Anoxia/hypoxia

Epilepsy: Classification

Generalized tonic clonic seizures

• Main seizure type: In -10% epileptics

• Tonic phase:

• Stiff, crying out, tongue bite, apnea, cyanosed
• Increase heart rate, blood pressure 
• Fall, labored breathing, salivation

• Clonic phase:

• Intermittent clonic movements of muscles 
• Brief relaxations, involves all limbs 
• Incontinence at the end of clonic phase, lasts for few minutes

• Post-ictal period:

Drowsiness, confusion, headache, deep sleep

Causes of Epilepsy

• Idiopathic: 72%
• Can be determined: 28% case

Determined causes:

     - Inherited genetic:

     - Acquired :Trauma, Neuro surgery. Inflammatory, Metabolic, Infections, Tumor, Toxic disorders, drugs
     - Congenital: Inborn error of metabolism.
     - Withdrawal of drugs:

Alcohol

  Barbiturates

  Anti-Epileptics

  Benzodiazepines

Management

• First priorities:

- Attention to vital signs 

- Respiratory and cardiovascular support 

- Treatment of seizures if they resume

• To be followed by:

Management of life-threatening conditions CNS infection, metabolic derangement and drug toxicity

• When the patient is not acutely ill:

Evaluation should initially focus on whether there is a history of earlier seizures

Anti Epileptic Drugs (AED) Classification

• Older AEDs:

- Phenobarbital, Phenytoin, Primidone 

- Ethosuximide , Carbamazepine , Valporate

• Newer AEDs:

- Lamotrigine, Topiramate, Tiagabine

- Oxcarbazepine, Zonisamide, Levetiracetam

- Vigabatrin, Felbamate, Pregabalin

- Rufinamide, Lacosamide, Stiripentol, Clobazam

- Eslicarbazepine, Ezogabine, Perampanel

Seizure: Types and choice of  AEDs

Facilitation of GABA mediated Chloride channel opening

Drugs acting through this mechanism are

• Barbiturate

• Benzodiazepine

• Vigabatrin

• Valproate

• Gabapentin

Glutaminergic synapse

• Type: Excitatory 
• Permeable to: Na+, Ca2+ and K+
• Blocked by:

Magnesium ions in resting state

• Enhancement:

Glycine (GLY) binding enhances the ability of GLU or NMDA to open the channel

• Agonists:

NMDA, AMPA, Kianate

Ethosuximide

• Mechanism of action:

- It has an important effect on Ca 2+ currents, reducing the low-threshold (T-type) current.

• Pharmacokinetics:

- t1/2 :40 hours

- Metabolism: Hydroxylation inactive products

• Adverse reactions:

- Gastric distress including pain, nausea, and vomiting

• Dose: 20-30mg/kg/day