Analyzing health records, investigators compared almost 17,000 patients who had undergone bariatric surgery with more than 620,000 individuals with obesity who had not undergone the surgery.
During a minimum 3-year follow-up period, the surgery group had a 45% higher risk of developing epilepsy than the nonsurgery group. Moreover, patients who had a stroke after their bariatric surgery were 14 times more likely to develop epilepsy than those who did not have a stroke.
“When considering having bariatric surgery, people should talk to their doctors about the benefits and risks,” senior investigator Jorge Burneo, MD, professor of neurology, biostatistics, and epidemiology and endowed chair in epilepsy at Western University, London, told this news organization.
“While there are many health benefits of weight loss, our findings suggest that epilepsy is a long-term risk of bariatric surgery for weight loss,” Dr. Burneo said.
The findings were published online in Neurology.
Unrecognized risk factor?
Bariatric surgery has become more common as global rates of obesity have increased. The surgery has been shown to reduce the risk for serious obesity-related conditions, the researchers note.
However, “in addition to the positive outcomes of bariatric surgery, several long-term neurological complications have also been identified,” they write.
One previous study reported increased epilepsy risk following gastric bypass. Those findings “suggest that bariatric surgery may be an unrecognized epilepsy risk factor; however, this possible association has not been thoroughly explored,” write the investigators.
Dr. Burneo said he conducted the study because he has seen patients with epilepsy in his clinic who were “without risk factors, with normal MRIs, who shared the history of having bariatric surgery before the development of epilepsy.”
The researchers’ primary objective was to “assess whether epilepsy risk is elevated following bariatric surgery for weight loss relative to a nonsurgical cohort of patients who are obese,” he noted.
The study used linked administrative health databases in Ontario, Canada. Patients were accrued from July 1, 2010, to Dec. 31, 2016, and were followed until Dec. 31, 2019. The analysis included 639,472 participants, 2.7% of whom had undergone bariatric surgery.
The “exposed” cohort consisted of all Ontario residents aged 18 years or older who had undergone bariatric surgery during the 6-year period (n = 16,958; 65.1% women; mean age, 47.4 years), while the “unexposed” cohort consisted of patients hospitalized with a diagnosis of obesity who had not undergone bariatric surgery (n = 622,514; 62.8% women; mean age, 47.6 years).
Patients with a history of seizures, epilepsy, epilepsy risk factors, prior brain surgery, psychiatric disorders, or drug or alcohol abuse/dependence were excluded from the analysis.
The researchers collected data on patients’ sociodemographic characteristics at the index date, as well as Charlson Comorbidity Index scores during the 2 years prior to index, and data regarding several specific comorbidities, such as diabetes mellitus, hypertension, sleep apnea, depression/anxiety, and cardiovascular factors.
The exposed and unexposed cohorts were followed for a median period of 5.8 and 5.9 person-years, respectively.
‘Unclear’ mechanisms
Before weighting, 0.4% of participants in the exposed cohort (n = 73) developed epilepsy, versus 0.2% of participants in the unexposed cohort (n = 1,260) by the end of the follow-up period.
In the weighted cohorts, there were 50.1 epilepsy diagnoses per 100,000 person-years, versus 34.1 per 100,000 person-years (rate difference, 16 per 100,000 person-years).
The multivariable analysis of the weighted cohort showed the hazard ratio for epilepsy cases that were associated with bariatric surgery was 1.45 (95% confidence interval, 1.35-1.56), after adjusting for sleep apnea and including stroke as a time-varying covariate.
Having a stroke during the follow-up period increased epilepsy 14-fold in the exposed cohort (HR, 14.03; 95% CI, 4.25-46.25).
The investigators note that they were unable to measure obesity status or body mass index throughout the study and that some obesity-related comorbidities “may affect epilepsy risk.”
In addition, Dr. Burneo reported that the study did not investigate potential causes and mechanisms of the association between bariatric surgery and epilepsy risk.
Hypotheses “include potential nutritional deficiencies, receipt of general anesthesia, or other unclear causes,” he said.
“Future research should investigate epilepsy as a potential long-term complication of bariatric surgery, exploring the possible effects of this procedure,” Dr. Burneo added.
Risk-benefit discussion
In a comment, Jacqueline French, MD, professor of neurology at NYU Grossman School of Medicine, and director of NYU’s Epilepsy Study Consortium, said she was “not 100% surprised by the findings” because she has seen in her clinical practice “a number of patients who developed epilepsy after bariatric surgery or had a history of bariatric surgery at the time they developed epilepsy.”
On the other hand, she has also seen patients who did not have a history of bariatric surgery and who developed epilepsy.
“I’m unable to tell if there is an association, although I’ve had it at the back of my head as a thought and wondered about it,” said Dr. French, who is also the chief medical and innovation officer at the Epilepsy Foundation. She was not involved with the study.
She noted that possible mechanisms underlying the association are that gastric bypass surgery leads to a “significant alteration” in nutrient absorption. Moreover, “we now know that the microbiome is associated with epilepsy” and that changes occur in the gut microbiome after bariatric surgery, Dr. French said.
There are two take-home messages for practicing clinicians, she added.
“Although the risk [of developing epilepsy] is very low, it should be presented as part of the risks and benefits to patients considering bariatric surgery,” she said.
“It’s equally important to follow up on the potential differences in these patients who go on to develop epilepsy following bariatric surgery,” said Dr. French. “Is there a certain metabolic profile or some nutrient previously absorbed that now is not absorbed that might predispose people to risk?”
This would be “enormously important to know because it might not just pertain to these people but to a whole other cohort of people who develop epilepsy,” Dr. French concluded.
The study was funded by the Ontario Ministry of Health and Ministry of Long-Term Care and by the Jack Cowin Endowed Chair in Epilepsy Research at Western University. Dr. Burneo holds the Jack Cowin Endowed Chair in Epilepsy Research at Western University. The other investigators and Dr. French have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.