June 2026
Cancer risk may be increased after unexplained first seizure, finds study
By Rebecca Jenkins
First-time seizures are linked to an elevated short-term risk of cancer, a large population-cohort study finds.
Seizures were a known cancer complication, researchers wrote in JAMA Neurology, but it was unclear if they could also be the first sign of undiagnosed cancer.
In a study using Danish medical registries’ data, they identified almost 50,000 adults diagnosed with a first-time seizure between January 1996 and December 2022.
Of these, 20,648 (41.4%) were women, the median age at seizure diagnosis was 51.5 years and most had seizures recorded as the primary reason for the index hospital contact.
A total of 2022 cancers were observed within the first year of follow up after a first-time seizure, including 1172 neurological and 850 non-neurological cancers.
This translated to a one-year absolute risk (AR) of 2.4% for neurological cancer with a standardised incidence ratio (SIR) of 76.1 relative to the general population. This effect was largely driven by an increased risk in brain cancers (AR, 1.7% and SIR, 98.7).
For non-neurological cancers, the one-year AR was 1.7% and the SIR was 2.32.
The risk remained slightly elevated over the long term after a first-time seizure for both types of cancer, the study found.
‘These findings indicate that first-time seizures may serve as an early clinical sign of both neurological and non-neurological occult cancers, thus highlighting the importance of considering broader diagnostic assessments for persons with first-time seizures,’ the study authors concluded.
Discussing the findings, Dr Julia Thompson, Neurologist at Chris O’Brien Lifehouse, Sydney, said that although cancer leading to seizures was an important consideration, it was not possible to draw any other conclusions about causation given the study’s observational design.
The long-term increase in cancers was modest (SIR, 1.3) – a small effect that might relate to age, frailty, smoking, alcohol use, other vascular risks and socioeconomic or healthcare bias, she said.
There were also several limitations, including that the findings might reflect reverse causality.
‘However, I like the study because it does show that a truly unexplained new seizure in adulthood, especially middle age and older age, can be the first clue to systemic malignancy,’ Dr Thompson said.
‘It reinforces that first seizure should prompt proper CT or MRI imaging regardless of age – that is the big take-home message.’
In addition to imaging, a thorough history should be taken addressing all risk factors for epilepsy and cancer, such as smoking and family history, together with a neurological examination.
Unexplained seizure may relate to cancer, especially if there were also unexplained constitutional symptoms, such as electrolyte changes, focal seizures or cognitive changes.
‘But the paper shouldn’t lead to over-reaction, as seizures are common and can be symptoms of many conditions and causes,’ Dr Thompson said.
‘It’s just important to keep cancer-associated causes on the list.’