TOPLINE: 

First-time seizures were associated with a higher short-term relative risk for cancer but only a slightly higher long-term risk, according to a nationwide cohort study of nearly 50,000 Danish adults with first-time seizure. However, this may reflect reverse causality (seizures triggered by undiagnosed cancers) or increased detection due to more intensive diagnostic evaluation after a first-time seizure, the study authors noted.

METHODOLOGY: 

• Seizures are a known complication of cancer, but it remains unclear whether first-time seizures may be a sign of an undiagnosed neurologic or non-neurologic cancer.
• To assess cancer risk in patients with first-time seizures compared to the general population, researchers conducted a nationwide population-based cohort study using Danish medical registries from January 1996 through December 2022.
• The study included 49,894 persons aged 18 years or older with a first-time hospital seizure diagnosis and no history of cancer or epilepsy. Median age at seizure diagnosis was 51.5 years and median follow-up was 5.7 years.
• The primary outcome was absolute risk for cancer and standardized incidence ratios (SIRs) relative to the general Danish population, calculated for all cancers and site-specific cancers within 1 year, 1-5 years, and 5-20 years after first seizure. SIRs were calculated as the ratio of observed to expected cancer cases based on national incidence rates according to sex, age, and year of diagnosis.

TAKEAWAY: 

• In this population, the 1-year absolute risk was 4.1% overall, 2.4% for neurologic cancers, and 1.7% for non-neurologic cancers. Risk for neurologic cancers was roughly 76-fold higher than expected in the general population, despite a modest absolute risk of 2.4%, and 2.3-fold higher for non-neurologic cancers.
• However, the risk for cancer overall was only slightly elevated over the longer term (SIR, 1.18 at 1-5 years and 1.33 at 5-20 years).
• Within the first year of follow-up, brain cancers showed the greatest increase in risk (absolute risk, 1.7%; SIR, 98.7), and among non-neurologic cancers, lung, bronchial, and tracheal cancers had the largest relative risks (absolute risk, 0.6%; SIR, 5.94). The relative risk of any cancer within the first year was highest among younger individuals aged 18-29 years (absolute risk, 1.4%; SIR, 27.9).
• Notably, the observed increase in cancer risk within the first year after a first-time seizure may reflect reverse causality, where seizures are triggered by undiagnosed cancers, or increased diagnostic evaluation following first-time seizures, which may lead to earlier disease detection, the authors explained.

IN PRACTICE:

“These findings indicate that first-time seizures may serve as an early clinical sign of both neurological and nonneurological occult cancers, thus highlighting the importance of considering broader diagnostic assessments for persons with first-time seizures,” the study authors concluded.

SOURCE:

The study, led by Andreas Lund Pedersen, BSc, Department of Clinical Epidemiology, Center for Population Medicine, Aarhus University and Aarhus University Hospital in Aarhus, Denmark, was published online on April 27 in JAMA Neurology.

LIMITATIONS:

Diagnostic misclassification could arise if persons with established epilepsy were initially assigned an unspecified seizure diagnosis code, potentially leading to overestimation of cancer risk in the cohort. Unmeasured or unknown factors such as socioeconomic status, lifestyle habits, genetic predispositions, or underlying medical conditions associated with seizure risk may have affected the observed associations. Persons with underlying conditions, such as Alzheimer’s disease, may have undergone less extensive diagnostic evaluation because of their existing comorbidities, which could affect cancer detection rates.

DISCLOSURES:

Henrik Toft Sorensen, MD, PhD, DMSc, DSc, disclosed that the Department of Clinical Epidemiology at Aarhus University receives funding for other studies in the form of institutional research grants administered by Aarhus University and makes paid evaluations for the European Research Council, the Independent Research Fund Denmark, the Norwegian Research Council, and the University of Oslo outside the submitted work. No other disclosures were reported by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.