Neuroscience/Objectives/Lecture 49

From PhysioWiki

Epilepsy, seizures, and the EEG

Understand the role of the electroencephalogram and how it detects the activity of neurons.

The EEG measures the collective activity of cortical neurons and helps identify the type and location of neuronal activity. It records the electrical fields created by synaptic currents from pairs of electrodes placed on the scalp. The amplitude of the signal represents cortical synchrony. Seizures result from the synchronous activity of neurons.

Define seizure, epilepsy, and aura.

Seizure

A transient disturbance in cerebral function due to abnormal paroxysmal discharge. Prevalence: 1 in 20 will experience a seizure in their lifetime. Preceded by an aura, a feeling/experience immediately before a seizure (indicates seizure focus in simple partial seizures). Risk factors include:

• Massive sleep deprivation
• Excessive stimulant use
• Withdrawal from sedatives (drugs/ethanol)
• Substance abuse
• Fever
• Hypoglycemia
• Electrolyte imbalance
• Hypoxia
• Medication
  • Iodinated contrast
  • Anticholinesterases
  • Antihistamines
  • Antipsychotics
  • Beta blockers

Status epilepticus, a prolonged seizure, lasts 30 minutes. It is a medical emergency because while the brain can homeostatically compensate for brief seizures, these compensatory mechanisms fail during prolonged seizures.

Alcohol withdrawal seizures affects 15% of alcoholics 24-48 hours after withdrawal.

Febrile seizures are most common in children (2-4%) and usually occur with high temperature. They are usually brief, generalized seizures.

Psychogenic seizures are non-epileptic spells that resemble seizures but are not actually seizures. Psychogenic seizure patients have multiple seizure patterns whereas neurogenic seizures have single patterns by and large. Psychogenic seizures also differ in that they are not followed by a postictal period (ie, the event is often recalled by the patient).

Syncope is caused by reversible cerebral hypoxia and involves a loss of muscle tone. It may be difficult to distinguish between syncope and seizures.

Epilepsy

One of many illnesses characterized by recurrent and non-provoked seizures. Prevalence: 1% of population.

Identify factors contributing to epileptogenesis.

Epileptogenesis is characterized by three phases:

1. Brain damage (eg, from trauma, stroke, tumor, status epilepticus)
2. Latency phase (from weeks to years following initial brain insult)
3. Epilepsy (start of recurrent, unprovoked seizures)

Mutations may contribute to epileptogenesis:

• timing of developmental processes
• distribution of genes in neurons and brain
• subsets of target neurons
• compensatory processes (eg, synaptic pruning)

Etiology of epilepsy:

• Idiopathic
• Cerebrovascular
• Developmental
• Head trauma
• Brain tumor
• Infection
• Other

Identify the main classification of seizures and types of epilepsy.

• Partial seizures (local onset)
  • Simple partial (consciousness intact)
  • Complex partial (consciousness impaired/lost)
  • Secondary generalized seizures
• Generalized seizures (without local onset)
  • Absence (petit mal; usually focused in the thalamus; common in children)
  • Myoclonic (brief jerk)
  • Clonic
  • Tonic
  • Tonic-clonic (eg, grand mal)
  • Atonic

Identify the cellular underpinnings of seizures.

Neurons in a seizure focus share a common paroxysmal depolarizing shift, which is the physiological basis for the interictal spike on the EEG.

Generalized seizures are characterized by a three-second spike and wave pattern on the EEG. They are believed to originate in the thalamus, as synchronous cortical activity depends on thalamic input. Thalamic neurons that fire in the oscillatory (bursting) state are better equipped to synchronize larger populations of cortical neurons, leading to seizure. The generation of absence seizures involves relay and inhibitory cells of the reticular nucleus (RTN).

Describe basic principles of action of commonly used antiepileptic drugs.

Anticonvulsant drugs act on ion channels, neurotransmitter transporters, and neurotransmitter metabolic enzymes. The goal is to alter bursting properties of neurons to reduce the synchrony of cortical neuron firing. Anticonvulsants target partial seizures by impairing the recruitment of additional neurons. They block generalized seizures by interfering with the bursting ability of the thalamus.

Antiepileptic drugs:

• Bromides: enhance GABA_A activity
• Phenobarbital: enhances GABA_A activity; first non-toxic AED that is effective against grand mal seizures
• Phenytoin: Na⁺ channel blocker; non-sedating AED; first developed in a seizure drug screening process
• Valproate: Ca²⁺ channel blcoker; broad spectrum antiepileptic drug accidentally discovered in a drug screening

To treat absence seizures: valproate, ethosuximide, benzodiazepines.