Epilepsy Pathophysiology

By Dr Ananya Mandal, MD

What is a seizure?

A seizure is the clinical manifestation of epilepsy. This occurs basically due to excessive firing of the neurons and fast spread of these impulses over the brain. Thus there are two phenomenons in the pathophysiology of a seizure:-

  • hyper-excitability of a neuron
  • hyper synchronization

Hyper synchronization means that a hyper-excitable neuron leads to excessive excitability of a large group of surrounding neurons. This means that when a large electrical impulse is generated in one part of the brain from a focus of tissues millions of neurons in the brain fire excessively in addition bringing on a seizure.

Seizure is defined as an “involuntary alteration of behavior with or without loss of consciousness accompanied by an abnormal electrical discharge in the brain.”

Types of causation and epileptogenesis

Seizures may be due to a reason or reactive seizures or may be without cause (idiopathic). Reactive seizures occur in normal nonepileptic tissue. This may be seen in cases like those with hypoglycaemia who develop seizures due to excessive low blood sugar. Seizures may also occur in patients with encephalitis or meningitis due to inflammation of the brain tissues. Other causes include low blood sodium (hyponatremia), severe dehydration, low blood oxygen (hypoxia) etc.

Idiopathic epileptic seizures occur in chronically epileptic tissue. The steps by which a normal brain tissue become epileptic is called epileptogenesis. The normal neuronal networks become hyper-excitable networks. There are various factors which may lead to epileptogenesis. This includes genetic predisposition, infections or induced by medications.

Types of seizures

There are two types of seizures – partial and generalized. The difference between the two is of loss of consciousness. In partial cases a focal point of the brain is affected. In generalized seizures the impulses comes out from both sides of the brain at the same time.

Partial seizures may generalize; start from one site in the brain and spread to involve the whole brain. This is called secondary generalization.

Neuronal Excitability

Neuronal messages are transmitted by electrical impulses called the Action Potential. This is actually a net positive inward ion flux that leads to depolarization or voltage change in the neuronal membrane. The ions involved include sodium, potassium, calcium and chloride. Normally brain tissues prevent hyper excitability by several inhibitory mechanisms involving negative ions like chloride ions.

Disturbance in this normal excitability leads to hyper-excitability. In this state there is increases excitatory transmission of impulses and decreases inhibitory transmission. In addition there is alteration in the voltage gated ionic channels. These ion channels normally open when the voltage difference across the neuronal membrane is changed favourably.

Once activated the impulses flow via the neuronal circuits along the axons of the nerves. An action potential travels down the axon to the terminal buttons and then releases neurotransmitters in the synaptic cleft. This carries the action potential from one nerve to another.

Transmission

There are two types of transmission of impulses - excitatory and inhibitory. Excitatory transmission involves Glutamate that is the principal excitatory neurotransmitter in the brain. GABA or Gamma amino butyric acid is the principal inhibitory neurotransmitter in the brain.

There are two groups of glutamate receptors - Ionotropic (NMDA receptors) that modulate calcium and sodium channels and are responsible for fast synaptic transmission and Metabotropic (non NMDA receptors) that are for slow synaptic transmission. GABA is mediated via Chloride and Potassium channels.

Mechanism of seizure formation

  • Excitation of a group of nerves. This is caused by inward currents of Na, Ca and involvement of excitatory neurotransmitters like Glutamate and Aspartate.
  • Too little inhibition.
  • Epileptogenesis and hyperexcitability and hypersynchronization of neurons that facilitates spread. There has to be abnormal synchronization – a property of a population of neurons to discharge together independently. Alone, a hyperexcitable neuron cannot generate a seizure.

Electroencephalography or EEG

An EEG is graphical depiction of cortical electrical activity recorded by probes placed over the scalp. EEG helps in the diagnosis of epilepsy, sleep problems, altered consciousness etc. Typical EEGs show wave forms that help in diagnosis.

Reviewed by April Cashin-Garbutt, BA Hons (Cantab)

Sources

Further Reading

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