Better Fitness Linked to Lower Epilepsy Risk

Pauline Anderson

September 05, 2013

New research shows that low cardiovascular fitness in men at age 18 is strongly associated with increased risk for epilepsy later on, a finding that could have important implications for strategies to prevent or delay the progression of epileptogenesis.

The results suggest that cardiovascular fitness may contribute to an increased brain reserve capacity or somehow raise the seizure threshold.

"A working hypothesis is that cardiovascular fitness makes the brain resist the events that would otherwise set off epilepsy," said study author Elinor Ben-Menachem, MD, PhD, professor, neurology, Institute for Clinical Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden. "This study is the first indication that we should be looking into something like exercise, and the advantage is that it doesn't cost money."

The new report was published online September 4 in Neurology.

Inverse Relationship

The study included 1.17 million 18-year-old Swedish men who enlisted for mandatory military service between 1968 and 2005.

Researchers assessed cardiovascular fitness using the cycle ergometer test and translated the resulting values into a statistical score called the stanine score. Fitness was categorized as low (stanine score of 1 to 3), medium (stanine score of 4 to 6), and high (stanine score of 7 to 9). The fitness test, which is similar to a bicycle stress test, didn't change over the many years of the study, said Dr. Ben-Menachem.

Dr. Elinor Ben-Menachem

During an observation period that spanned 40 years, 6796 men (0.6% of the sample) were diagnosed with epilepsy, which corresponds to rates in the population as a whole in northern Sweden and in Europe.

The study found an inverse relationship between fitness and epilepsy, with the highest hazard ratio for epilepsy risk in the low cardiovascular fitness group (hazard ratio, 1.79; 95% confidence interval, 1.57 - 2.03; adjusted for calendar year, conscription test center, region, body mass index [BMI], and parental education).

The associations were still significant after controlling for familial factors. An analysis that included epilepsy in 1 or more brothers found that having at least 1 brother with epilepsy was associated with a more than 2-fold risk for future epilepsy, but cardiovascular fitness remained a significant predictor.

And the associations remained relatively unchanged over 4 different follow-up periods. This, said the authors, may be suggestive of permanent effects of cardiovascular fitness on the adolescent human brain. A person's brain is developing throughout childhood and even at the age of 18 years is not finished maturing, said Dr. Ben-Menachem.

Experts believe that traumatic brain injury (TBI) or cerebrovascular disease could contribute to epilepsy. In this study, the associations between cardiovascular fitness and epilepsy were only very slightly attenuated when adjusting for these prior diagnoses and for diabetes. Severe TBI was attenuated by 2.8%, cerebrovascular disease by 7%, and diabetes by 2.8%, and the significance remained.

Developing these conditions after conscription also didn't seem to affect outcomes.

"During the 40 years, we know that certain people had TBI, we know people had cardiovascular events, and we know some had diabetes because we could follow these from the registers in Sweden," said Dr. Ben-Menachem. "We also looked at the genetic part and even if we correct for all of those different aspects, we still get the people with high cardiovascular fitness having a lower risk compared to the lower cardiovascular group."

How fitness may prevent seizures is difficult to determine, but researchers believe it boosts brain function. "We know, especially from animal research, that physical activity does affect positively the structure and plasticity of the brain," said Dr. Ben-Menachem. "This is the first time in humans that we really see that having a high cardiovascular fitness at age 18 will affect the function and structure of the brain."

Epilepsy and Depression

Other research shows that physical fitness also has preventive effects on the risk for premature death and development of cardiovascular disease, diabetes, and depression. Epilepsy and depression are believed to have a complex bidirectional relationship whereby patients with depression have a higher risk of developing epilepsy. It's possible that a common pathogenic mechanism is present in both conditions that is positively influenced by cardiovascular fitness.

Dr. Ben-Menachem pointed to another paper (Br J Psychiatry. 2012;201:352-359) involving the same male Swedish cohort that showed low cardiovascular fitness at age 18 was associated with increased risk for serious depression in adulthood.

It's impossible to determine from this study the risk of developing epilepsy for someone with low cardiovascular fitness at age 18 who then becomes highly fit, said Dr. Ben-Menachem.

Do the current study findings have implications for people who already have epilepsy? That's also impossible to determine from the results, but Dr. Ben-Menachem referred to a study showing that only 10% of patients with epilepsy who were put on an exercise regimen had seizure exacerbation and that all participants felt better. She added that animal studies have shown that "you can delay onset of seizures, have milder seizures and fewer seizures with physical exercise."

Although the current study findings can't be extrapolated to the female population, Dr. Ben-Menachem feels the results for women would likely be similar.

A limitation of the study is that it included only TBI, cerebrovascular disease, and diabetes as possible confounders of epilepsy and not hypertension, myocardial infarction, central nervous system inflammation or infection, or brain tumors.

Dr. Ben-Menachem sees this group of military men as a potential minefield of research information. One ongoing study is looking at their risk for early dementia.

"This is amazing material," she said. "We have access to almost the entire male population born between 1950 and 1987. Our population is still pretty young, and these guys can be used over and over."

She's concerned about today's young people spending too much time playing video games and not getting enough physical activity and about schools systematically cutting out physical education programs.

She said she hopes this "very unique" study will stimulate new research on the effect of exercise on all neurologic diseases, not just epilepsy.

Results Encouraging

Reached for his opinion of this new research, Mill Etienne, MD, director of epilepsy for the Bon Secours Charity Health System, New York, New York, said the results are "encouraging," especially because a lot of research just focuses on medications and ways to treat seizures.

Epilepsy is not just a seizure disease; a person with this condition is dealing with a lot more than just seizures and should be viewed as a "whole person," said Dr. Etienne.

"When someone has temporal lobe epilepsy, although we might say the focus is the temporal lobe, that person has an overall brain disorder, so it's bigger than just that temporal lobe issue. The whole person is involved."

While he found the data "positive," it's still just 1 study showing a relationship between cardiovascular fitness and epilepsy risk.

"We need to get more data from different researchers, different groups, different cohorts, that reproduce these results," said Dr. Etienne. "I think for now I won't start calling poor cardiovascular health a risk factor for epilepsy, but what I would say to patients is that this is another reason to be healthy, to live a healthy lifestyle."

Dr. Ben-Menachem serves as chief editor for Acta Neurologica Scandinavica; is involved in sponsored research for which she served as primary investigator for Bial, UCB, and Eisai; received research support from Bial, UCB, and Eisai; and received institutional support from the Västra Götaland for research in neuromodulation.

Neurology. 2013;81:1051-1057. Published online September 4, 2013. Abstract

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