Abstracts

Older adults have the highest epilepsy incidence, and 25-50% of new onset cases in this population lack an identifiable cause, a condition referred to as late onset unexplained epilepsy (LOUE). There remains a paucity of literature on LOUE despite its high disease burden. The objective of this review is to systematically map and consolidate existing LOUE research to better delineate future research targets.

The systematic review was conducted according to 2020 PRISMA guidelines. We searched Medline, Cochrane, Embase, and Scopus for articles published from 1 January 1990 to 28 March 2025, using search terms: “aged”, “elder”, “senior”, “geriatric”, “older adult”, “late onset” or “adult onset”, and “epilep* or seizure* or convuls*”. Abstracts were screened for eligibility independently by two reviewers. To ensure consistency, a random sample of 25 titles was initially screened, requiring at least 75% agreement. Quantitative studies examining cohorts of >5 adults ≥ age 50 with new-onset epilepsy, published in English, Arabic, French, Mandarin, Portuguese, or Spanish, were included. Studies were excluded if their focus was etiology (e.g., post-stroke, tumor, infection, or dementia-related epilepsy) or chronic epilepsy (onset before age 50). Qualitative studies, reviews, gray literature, or case series with < 5 adults were excluded. Data were independently extracted by two reviewers into categories of epidemiology, etiologies, comorbidities, cognition, diagnostics, treatment, or outcomes.

Ninety-four studies were included. The most common age cutoff for defining LOUE was ≥ 60 (n=32, 34%), followed by ≥ 50 (n=22, 23%). Most were retrospective (n=69, 73%), single-center (n=70, 74%), cohort studies (n=90, 96%). There was a lack of epidemiological studies focused on incidence and prevalence of LOUE. Epidemiological studies provided a broader incidence of late onset epilepsy (LOE), ranging from 162 (onset > age 50) to 416 (onset > age 67) per 100000 person years. In cohort studies of LOE patients, the proportion with unknown etiology ranged from 6.5% to 61%. Most studies reported focal seizures as the most common seizure type (n=38, 40%), and vascular risk factors (particularly hypertension) as a common comorbidity. Interictal epileptiform abnormalities ranged from 8.2% to 92.3% of LOE patients; specific EEG findings in those with LOUE were rarely described. Imaging studies noted an association between LOUE and leukoaraiosis. Across studies that reported outcomes, an average of 76% of LOUE were on monotherapy, and ~84% achieved seizure freedom at 1–3 years of follow-up.

This systematic review highlights that most LOUE studies define late onset as ≥ age 60. Most studies suggest patients commonly present with focal seizures, exhibit a high burden of vascular comorbidities, often show interictal epileptiform discharges, and frequently achieve seizure control with monotherapy. However, significant gaps remain in understanding the epidemiology, clinical presentation, EEG features, etiology, and treatment options for this population, especially for the ~15% of patients who are drug resistant. Further research is needed to better define this population.