First-Time Seizures Linked to Higher Cancer Risk, Study Finds

First-time seizures were associated with a higher risk of neurologic and non-neurologic cancers within 1 year and beyond, a study of 50,000 patients in Denmark showed.

The absolute risk of neurologic cancers was 2.4% the first year after a first-time seizure occurred, and the standardized incidence ratio (SIR) relative to the general population was 76.1 (95% CI 71.8-80.6), reported Henrik Toft Sørensen, MD, PhD, DMSc, DSc, of Aarhus University Hospital in Denmark, and co-authors. The SIR represents the ratio of observed to expected cancer cases in a population.

For non-neurologic cancers, the absolute risk was 1.7% within the first year and the SIR was 2.32 (95% CI 2.17-2.48), Sørensen and colleagues reported in JAMA Neurology.

The risk of any cancer in the first year was 4.1% and the SIR was 5.30 (95% CI 5.07-5.54). Risks remained elevated over the long term: the absolute risk of any cancer was 3.5% at 1 to 5 years, and 13.4% at 5 to 20 years.

“The number of persons needed to examine to detect any cancer within the first year after a first-time seizure was 30, corresponding to identification of one additional cancer case for every 30 persons with a first-time seizure,” Sørensen and co-authors stated. “This number was 43 for neurological cancers and 103 for non-neurological cancers.”

No large population-based studies have specifically investigated first-time seizures in relation to cancer risk, the researchers noted.

“While seizures are a recognized presenting symptom of cancers of the central nervous system, the results of this study suggest that seizures may also be a presenting symptom of cancers of non-neurological origin as well,” co-author Holly Elser, MD, PhD, of the Hospital of the University of Pennsylvania in Philadelphia, told MedPage Today.

Primary brain tumors and metastatic lesions can trigger seizures by disrupting neural circuits, causing peritumoral inflammation, increasing intracranial pressure, and enhancing excitatory neurotransmission, the researchers observed.

“These mechanisms are likely to explain the markedly elevated short-term risk of brain cancers observed in our study,” Sørensen and co-authors pointed out. “The persistently elevated risks for non-neurological cancers, particularly lung cancer and colorectal cancer, may partly reflect the occurrence of brain metastases, which are common for these cancer types.”

The researchers evaluated data from nationwide Danish medical registries from 1996 through 2022, following 49,894 adults with a first-time seizure until cancer diagnosis (excluding nonmelanoma skin cancer), emigration, or death. Participants had no preceding cancer.

The median age at seizure diagnosis was 51.5 years and 41.4% were women. Nearly half (47.0%) of first-time seizure cases were admitted as inpatients, 37.8% presented to emergency departments, and 15.3% were seen in outpatient settings.

During the first year of follow-up, 1,172 neurologic cancers and 850 non-neurologic cancers were reported. Between 1 and 5 years, there were 87 neurologic and 1,226 non-neurologic cancers, and from 5 to 20 years, 112 neurologic and 2,120 non-neurologic cancers were recorded.

In the first year, brain cancers showed the largest relative risk increase (absolute risk 1.7%; SIR 98.7, 95% CI 92.2-105.6), the researchers noted. Among non-neurologic cancers, relative risks were highest for lung, bronchial, and tracheal cancers (absolute risk 0.6%; SIR 5.94, 95% CI 5.27-6.67) and for metastases and unspecified cancers in lymph nodes (absolute risk 0.1%; SIR 7.34, 95% CI 5.55-9.54).

“This study’s findings are consistent with those from prior research reporting high seizure incidences in specific primary brain tumors. However, those studies primarily investigated seizures occurring after a cancer diagnosis, whereas our study reversed the temporal order by examining the risk of cancer after the occurrence of a first-time seizure,” Sørensen and colleagues wrote.

“Furthermore, this analysis demonstrates that first-time seizures may also serve as an early clinical marker of occult non-neurological cancers, particularly in the short term,” they added.

Study limitations included possible misclassification of first-time seizures and unmeasured or unknown confounding variables, the researchers acknowledged.

“Although data on specific metastatic sites were unavailable, the over-representation of metastatic-stage cancers suggests that first-time seizures are more likely to be an early clinical sign of underlying metastatic or advanced disease than of nonmetastatic cancers,” they noted.