Seizure disorders

A seizure is defined as a temporary dysfunction of the brain consisting of an abnormal, excessive synchronous neuronal discharge. It may present as changes in consciousness and behavior, abnormal motor, sensory , autonomic or cognitive function. Symptoms such as aura, sense of deja vu, fear or abnormal smells may herald the onset of a seizure. Epilepsy is a disease of the brain that predisposes a person to recurrent unprovoked seizures. Revised definition for status epilepticus is seizure with 5 minutes or more of continuous clinical and/or electrographic seizure activity, or recurrent seizure activity without recovery between seizures.

Causes of seizures

• High fever
• Hyponatremia, diuretic use, hypernatremia, hypercalcemia
• Medications like bupropion, MAOI, SSRI, TCAs, INH, lidocaine, theophylline, tramadol, antipsychotics (chlorpromazine, clozapine)
• Head trauma, previous scarring
• Brain tumors
• Recreational drugs like cocaine, amphetamines
• Alcohol abuse, alcohol withdrawal
• Epilepsy
• CNS infections like meningitis, encephalitis
• Hepatic encephalopathy
• Stroke, SAH
• Hypoxia
• Hypoglycemia, metabolic disorders

Types of seizures

Tonic-clonic seizures manifest as tonic phase followed by clonic phase. They start in the primary motor or premotor cortex. Focal seizures are simple if there is no loss or disturbance of consciousness while they are called complex or discognitive, if consciousness is impaired or lost. Absence seizures may be typical (petit mal) or atypical (Lennox-Gastaut syndrome). Myoclonic seizures may be focal or generalized. The clinical manifestations of a focal seizure depend on the area of cortex involved. For example, a focal seizure arising from the occipital lobe may present with visual phenomena; from the precentral gyrus, with rhythmic clonic or tonic motor activity; and from the postcentral gyrus, with sensory symptoms, such as paresthesias and auditory cortex seizures may present with hearing music, voices or roaring sounds. Epileptic spasms are a type of seizure disorder that manifest by sudden extension or flexion of extremities, held for several seconds, and then recur in clusters e.g. infantile spasms.

Temporal lobe epilepsy is the most common cause of epilepsy. It is a partial complex or psychomotor epilepsy. These seizures begin with a visceral sensation or other aura and are followed by a state of impaired consciousness, automatic motor activities or convulsions. Aura may be visual, olfactory, cognitive like sense of Deja vu, sensory or emotional like anger, aggression etc. The EEG localizes the epileptogenic focus in the medial portion of the temporal lobe. Hippocampal sclerosis and neuronal loss by excitotoxicity is seen. Impaired GABAergic inhibition, enhanced synaptic excitation via axonal sprouting, and changes in ion channel distribution and function have all been implicated in the pathophysiology of temporal lobe epilepsy.

Febrile seizures are seen in children aged 6 months to 5 years of age. Simple febrile seizures are brief (<15 min), generalized, and do not recur within 24 h of the first one. Complicated febrile seizures are either prolonged (>15 min), have focal components (e.g., begins on one side of the body or involves lateralized eye deviation), or recur within 24 h. It may predispose to temporal lobe epilepsy in adult life. Any cause of fever including viral infections such as Roseola and influenza, MMR and DPT vaccinations can precipitate febrile seizures in susceptible individuals. Often a family history of febrile seizures is present.

Seizures are caused by an imbalance between excitation (glutamate mediated) and inhibition (GABA mediated) of the brain from genetic or acquired factors. Under normal circumstances, excitatory synaptic activity is tightly regulated by inhibitory interneurons. A variety of genetic or acquired factors that disrupt this regulation cause cortical networks to become hyperexcitable. Furthermore, neuropeptides released at synapses facilitate the spread of seizure. Mutations in ion channels like voltage gated K+ channels, neuronal Na+ channels (SCN1A mutations), GABA receptors may be present. For example, in generalized seizures, the defect may be abnormal sodium channels in cortical interneurons, allowing increased firing of downstream excitatory pyramidal neurons, which are released from inhibitory control. The pathophysiology of absence seizures involves altered function of thalamocortical circuits, with thalamic relay neurons firing abnormally, owing to calcium channel dysfunction. Mitochondrial diseases and autoantibodies are seen in some seizure disorders. Prolactin levels are elevated after generalized seizures.

In pseudoseizures, clinically seizure-like symptoms are seen without any EEG changes. About 10% of adults with epilepsy have bipolar disorder and up to 30% have depression. Persons with epilepsy are also at increased risk for early mortality and sudden unexplained death in epilepsy (SUDEP)

EEG in epilepsy