Clinical features and prognosis of first-ever acute symptomatic seizures due to acute systemic causes.

Objective: This study was undertaken to assess the clinical features and prognosis in patients with a first-ever acute symptomatic seizure due to an acute systemic cause (ASAS).

Methods: Patients with a first-ever ASAS were prospectively identified and compared to age- and sex-matched controls, and to patients with first-ever unprovoked seizure without obvious cause. Referrals were predominantly from local emergency departments. Patients underwent clinical assessment, routine electroencephalography (EEG), and neuroimaging. The primary outcome was the occurrence of a second seizure.

Results: Three hundred and ninety-three patients with ASAS were identified between 2000 and 2015. The commonest etiology was a prescribed drug (36%), with the remainder related to illicit drug use (23%), alcohol (17%), drug withdrawal (9.5%), metabolic derangement (9.5%), and drug overdose (5%). EEG showed epileptiform abnormalities in 10% of patients, and neuroimaging identified a nonacute epileptogenic lesion in 6%. The 2-year cumulative probability of any seizure recurrence was 28.7% (95% confidence interval [CI] = 24.1-33.2), for ASAS recurrence 19.4% (95% CI = 15.3-23.5), and for an unprovoked seizure 11.2% (95% CI = 8.0-14.4), compared to 47.6% (95% CI = 44.2-50.9) recurrence after first unprovoked seizure without obvious cause. Etiology was not predictive of recurrence, other than an increase in the likelihood of an acute symptomatic recurrence for alcohol withdrawal seizures. Independent risk factors for unprovoked seizure recurrence were epileptogenic lesion on imaging, with a hazard ratio (HR) of 3.8 (95% CI = 1.7-8.7), and epileptiform abnormality on EEG (HR = 2.2, 95% CI = 1.0-5.1), but when present the 2-year cumulative probability of an unprovoked recurrence was only 23.9%. Furthermore, patients without these risk factors still had a 2-year likelihood of a subsequent unprovoked seizure of 8.0% (95% CI = 4.7-11.4), compared to 0.1% for any seizure in controls.

Significance: The risk of an unprovoked seizure following ASAS was far higher than expected if simply attributable to a reversible acute symptomatic cause, and this has practical relevance when counseling patients.