First seizure in adults

A first seizure in adults refers to a single, spontaneous episode of abnormal neuronal activity resulting in transient neurologic dysfunction. It may be classified as either provoked (acute symptomatic) or unprovoked, depending on the presence of an identifiable acute cause.

Seizures arise from abnormal, synchronous electrical discharges within the cerebral cortex, reflecting an imbalance between excitatory and inhibitory neuronal activity. Mechanistically, seizures involve recurrent excitatory synaptic activity and loss of coordinated signaling between neuronal populations. This cortical disorganization leads to transient neurologic dysfunction. In prolonged seizures, normal homeostatic mechanisms may become impaired, exacerbating metabolic stress, altering cerebral perfusion, and increasing the risk of neuronal injury. The pathophysiology varies depending on whether the seizure is provoked (due to acute metabolic, infectious, or structural insults) or unprovoked, which may involve chronic or idiopathic mechanisms including genetic predisposition or remote cerebral injury.

The incidence of a first seizure in adults ranges from 23 to 61 cases per 100,000 person-years, with the risk increasing significantly after age 55 and peaking in individuals older than 75. The lifetime risk of experiencing a seizure is up to 10%, while only about 3% of adults are ultimately diagnosed with epilepsy. The rate of first seizures is higher in low- and middle-income countries, which account for around 80% of the global epilepsy burden.

Approximately 40% of first seizures in adults are provoked by identifiable acute factors. Common causes include metabolic disturbances (hypoglycemia, hyponatremia, hepatic or renal failure), infections (meningitis, encephalitis), structural brain abnormalities (stroke, traumatic brain injury, tumors), and toxic exposures (alcohol withdrawal, drug intoxication). Inflammatory conditions such as SLE and autoimmune encephalitis may also contribute. Other reversible factors include prescribed medications, sleep deprivation, and substance misuse. Identifying a provoking factor is critical for prognosis and treatment planning, as provoked seizures have a lower risk of recurrence once the underlying cause is resolved. Unprovoked seizures occur without an acute precipitating factor and are more common in younger adults. They are classified as either idiopathic, with no identifiable cause, or secondary to preexisting or remote CNS injury. Known risk factors include prior traumatic brain injury, congenital neurological conditions such as cerebral palsy, and a history of CNS infections. These underlying abnormalities contribute to a higher risk of seizure recurrence and the potential diagnosis of epilepsy.

The clinical presentation of a first seizure depends on the site of onset and the pattern of spread. Generalized seizures often begin without warning, while focal seizures may be preceded by an aura, such as a rising epigastric sensation, déjà vu, or unusual tastes or smells. The absence of an aura does not exclude focal onset, especially in seizures originating from the frontal lobe. Convulsive seizures typically begin with a tonic phase of limb stiffening, followed by a clonic phase of rhythmic jerking. These events last approximately 1-3 minutes and may involve open eyes, apnea, and cyanosis. Postictal recovery is often marked by confusion, fatigue, and signs such as lateral tongue biting. Psychogenic nonepileptic seizures, also known as pseudoseizures, are seizure-like symptoms that are not associated with abnormal brain electrical activity.

Adults experiencing a first unprovoked seizure have a 21% to 45% risk of recurrence within the first 2 years, with approximately one-third experiencing a second seizure within the first year. The risk is highest in the initial months following the first event. Factors associated with increased recurrence include a prior brain insult (such as stroke or trauma), epileptiform abnormalities on EEG, structural brain abnormalities on imaging, and a seizure occurring during sleep. Initiating antiseizure medication immediately after the first seizure reduces the risk of recurrence by approximately 35% over the first 2 years. However, early treatment does not improve long-term remission rates beyond 3 years compared to delayed treatment.