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Body and mind

Infections are associated with a greatly increased risk of epilepsy

An epileptic seizure can be a disturbing experience. Globally, about 50 million people have epilepsy, but only half of them know why. A new research project shows that the risk of developing epilepsy increases by 78% if a person has been hospitalized with an infectious disease. Additional hospitalizations for infection increase the risk further.

From spacing out involuntarily for a few seconds to strong contractions in all the body’s muscles. Impaired ability to see, hear or taste. Blackouts and involuntary urination and defecation. All of these can result from the abnormal and synchronous electrical discharges in the brain’s neurons characteristic of epilepsy. Many people have epilepsy without knowing why. Now, however, researchers have come one step closer to understanding the causes.

“Many people with epilepsy know why they have it. For example, they may have had a severe head injury, stroke, brain tumour or some other form of brain damage. But about half of those with epilepsy do not know why they have it. We analysed health data collected over a period of more than 30 years and found that many types of infections correlate with an increased risk of epilepsy,” explains Frederik Ahlers, researcher and doctor, Department of Neurology, Aarhus University Hospital.

Increasing risk with the number of hospitalizations

Epilepsy is the result of abnormal neuronal activity in the brain. Brain diseases are therefore a common cause of epilepsy. However, because about half the people with epilepsy have never had a brain disease that can explain why they have epilepsy, the researchers wanted to create new knowledge about why people develop epilepsy.

Previous studies demonstrated a link between epilepsy and certain pathogens such as the parasite that causes toxoplasmosis but, as far as the researchers know, no one had investigated the links between such a broad range of infectious diseases and epilepsy.

“Several recent studies have suggested an association between specific types of infection and developing epilepsy. However, in this study we wanted to examine a wide spectrum of infections and determine whether they were associated with an increased risk of developing epilepsy later in life. We therefore analysed data from nearly 2 million Danes, using diagnoses from the Danish National Patient Registry as well as data from other registries.”

Of these 2 million people, about 26,000 had been diagnosed with epilepsy at some time, and 32% of these had previously been admitted to hospital with an infection.

“We were very surprised about the great difference between the people who had been hospitalized with an infection and those who had not. People hospitalized with an infection at least once had a 78% higher risk of epilepsy compared with individuals who had never been hospitalized with an infection. And this risk increases with the number of hospitalizations. After eight hospitalizations for infection, the risk is 5–6 times greater.”

Epilepsy linked with mental disorders

Possibly the most surprising aspect of the study was that all infections, not just specific types, seem to increase the risk of developing epilepsy. The increase in risk was highest for infections in the central nervous system (including the brain), but infections in other parts of the body – such as the respiratory system or the gut – were also associated with a much greater risk of epilepsy.

“This may suggest that the increased risk of epilepsy stems from the immune response associated with the infection rather than from the infection itself. Previous research has shown that infections and inflammation can increase the permeability of the blood–brain barrier, and brain-reactive antibodies may be able to reach the central nervous system and thereby damage the brain. However, this is just one possible explanation.”

Other recent studies have suggested that infections also increase the risk of developing several mental disorders such as schizophrenia. The research also shows that these mental disorders are more common among people with epilepsy than among the general public.

“Based on our results, we hypothesize that the inflammatory processes that occur in relation to infections may damage the brain, increasing the risk of epilepsy. However, we cannot conclude with certainty that the association is causal. More research is needed to clarify the reasons for the link we found between infections and epilepsy.”

Infections and risk of epilepsy in children and young adults: a nationwide study” has been published in Epilepsia. In 2016, the Novo Nordisk Foundation awarded a grant to Jakob Christensen, Clinical Associate Professor, Department of Neurology, Aarhus University Hospital for the project Epilepsy and Psychiatric Comorbidity (EpiPsyk) – Genetic and Environmental Causes and Consequences of Epilepsy and Psychiatric Comorbidity.

Jakob Christensen
Clinical Associate Professor
In his research Jakob Christensen incorporates data which combines information from Danish social and health registers and biobanks. Biobanks have gathered many millions of biological samples from the Danish healthcare service. The samples are available to researchers such as Jakob Christensen, who share the goal of developing new medical treatment for patients with epilepsy. By combining data from both person registers and bioregisters, Jacob Christensen hopes to find the causes of the coherence between the two forms of disease. These have not yet been discovered, and could e.g. be risk factors that emanate from a patient's surrounding environment or their genes.