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Trembling under control

Doing physical exercises and consuming Omega-3 emerge as complementary treatments for epilepsy

Two Epileptic Women Aided By Four Men / © Bettmann/CORBIS/Corbis (DC)/Latinstock Esper Cavalheiro was sweating; he was working out at night in a health center alongside a trainer who never stopped asking about the functioning of the brain, neurons and the research that he was coordinating at the Federal University of São Paulo (Unifesp). In the face of such endless curiosity, Cavalheiro kindly asked: “Why not come and do a post-graduate degree with me.” Ricardo Arida, the person asking the question began to his post-graduate studies that same year, 1992. Since then, bringing together his training in physical education with what he learned doing his Master’s and doctorate, he has both made studies and followed such studies on laboratory animals and on humans. This is now allowing researchers in the area to recommend the practice of regular exercise of medium intensity – such as walking or running – to help control epilepsy, a neurological disorder characterized by intense electrical discharges in the brain, from which nearly 4 million people of all ages suffer in Brazil, the equivalent of 2% of the population.

The benefits of physical activity can be extended by a second, complementary therapy: the consumption of combinations of polyunsaturated fatty acids, like Omega-3 found in nuts and fish and used as a food supplement for strengthening the heart. Fulvio Scorza, from the Cavalheiro group, in collaboration with colleagues from other universities, has shown that daily doses of one to three grams of Omega-3 may protect or even stimulate the formation of neurons in the hippocampus, an area of the cerebral cortex associated with learning and the acquisition of memory, which is damaged in some forms of epilepsy. In experiments with animals and humans, the Omega-3, as much as the physical exercise, reduced the intensity and frequency of epileptic seizures, the sudden muscle contractions that represent the most visible face of epilepsy.

Arida entered this line of work in 1998. That was when, while still doing his PhD, he saw that rats accustomed to running on a treadmill, had 50% fewer induced epileptic seizures than sedentary rats. Now, as a professor at Unifesp, he was tutor for a study by Fabio Camilo on 17 people with epilepsy and 21 healthy people, published in December 2009 in the journal Archives of Neuropsychiatry, showing that even strenuous exercise can be beneficial in helping contain the crises. “The indication of physical exercise to treat epilepsy goes against long-held beliefs,” says Cavalheiro, adding that people with epilepsy are usually advised to undertake little activity and remain reclusive, at the risk of aggravating the crises.

Physical activity can appease the social and psychological effects generated by the crises. People who suffer from epilepsy tend to isolate themselves from social contact for fear that the emergence of crises in public might prove to be an embarrassment for those who don’t live with this problem. Isolation, in turn, may cause depression or anxiety. There are limits, however, to physical activity. “People who have epilepsy are not going to go mountain climbing, or swimming, because a crisis could be dangerous in these situations,” warns Arida, “but they can participate in other sports activities and return to a normal life, even though they are unable to stop the medication that prevents the crises.” People with epilepsy will perhaps welcome these possibilities. A survey he coordinated in 2003 showed that people with epilepsy believed that practicing sports could favor their treatment. Of the 100 people interviewed (58 men and 42 women), 51 were already practicing some physical activity, although not regularly; 85 did not believe that sports could trigger crises, 15 had been forbidden by doctors to do any physical activity and 14 had been warned by relatives and friends to stay away from running tracks and sports fields. “It’s worth planning a physical exercise program specifically for people with epilepsy,” proposes Arida.

Engraving of a woman having an epileptic fit/NATIONAL LIBRARY OF MEDICINE/SCIENCE PHOTO LIBRARY/SPL DC/Latinstock The movements that make you sweat regulate the production of neurotransmitters – the chemical messengers between neurons – and of hormones, thereby reducing epileptic seizures, according to a study by Arida and other researchers from Unifesp, the University of São Paulo (USP) and the University of Mogi das Cruzes (UMC), published in November 2009 in the journal Epilepsy & Behavior. According to Arida, an experiment recently completed at Unifesp indicated that physical exercise, whether voluntary or enforced – in addition to the better known effects, stimulating the release of substances called endorphins, which cause a feeling of well-being – doubled the amount and length of the arms of the neurons in the hippocampus of rats, thus facilitating communication among neurons.

Omega-3 seems to protect the nerve cells in at least two other ways. This first is by stimulating the production of parvalbumin, a protein that acts with the gamma-aminobutyric acid (Gaba) neurotransmitter, which inhibits the electrical activity of neurons. The second is linked to calcium ions (electrically charged atomic particles). “With the epileptic seizure, the membrane of the neurons becomes more permeable and lets more ionic calcium enter, which, in excess, can be toxic to cells”, comments Scorza, one of the organizers of the 4th Latin-American Epilepsy Summer School (Lasse), which brought together some 100 specialists between February 1 and10 in Guarulhos, in the Greater São Paulo region.

By balancing the electrical activity of neurons, Omega-3 should also help to reduce sudden death in epilepsy. The team from Unifesp has been investigating this type of premature death for years, which is two or three times more common in people with epilepsy than in those without it. One explanation is that the electrical imbalance of brain neurons may expand and disrupt the functioning of the heart. Another possibility, which Scorza, Cavalheiro and other researchers from Unifesp presented in January in Medical Hypotheses, is that a lack of vitamin D may contribute to cardiac arrhythmia, epilepsy and sudden death. In this case, the answer is simple: just take more sun, which intensifies the production of vitamin D by the organism. Vitamin D, they suggest, can also function as a regulator for the electrical activity of neurons.

For at least five years a series of tests in people has shown that Omega-3 may reduce the risks of epileptic seizures and sudden death. Some studies have shown temporary benefits, according to Scorza, “perhaps because the dose was low,” one gram of Omega-3 per day. Higher doses have led to clearer and more prolonged results. Marly Albuquerque, from the University of Mogi das Cruzes (UMC), together with the Unifesp team, coordinated a study in which nine people with epilepsy, in whom regular drugs had little effect, took a daily dose of three grams of Omega-3, plus their antiepileptic medication, for six months. Marly observed a 75% reduction in seizure frequency – from everyday they became weekly. “What was most remarkable were the gains in quality of life, with more socializing,” she said.

Since there are already a dozen effective drugs against epilepsy, to which these complementary therapies can now be added, treatment has ceased be the most difficult thing. “Amazingly, the most difficult thing is diagnosing the epilepsy and preventing people from taking the wrong drugs for years,” says Cavalheiro, coordinator-general of Lasse. Epilepsy can be missed even by experts because it is present in many different ways in childhood, adulthood or in old age. In babies and children, it may be expressed only through a strong blinking of the eyes or one to two-second contractions of the muscles in one of the hands. “Often doctors cannot diagnose seizures in infants due to lack of equipment and experience,” said Perrine Plouin, Hospital Saint Vincent de Paul, in Paris, in one of the Lasse presentations. It is only after 7 years old that children have epileptic seizures similar to those in adults, with involuntary, rapid and arrhythmic movements of the arms, legs, neck and shoulders.

To complicate matters, crises can result from various stimuli. On December 16, 1997, scenes of intense and vibrant red in the Pokemon cartoon triggered epileptic seizures in 685 children in Japan.  Plouin told of a girl less than 1 year old who had seizures, expressed only by irregular movements of the eyes, when she entered the bathtub with water at a temperature close to 37o C. Elza Yacubian, from Unifesp, described another rare form of epilepsy triggered by reading under stress, such as texts in an unknown language, which was only visible by contraction of the jaw muscles.

Crises are rare – and the epilepsy is more difficult to detect – in the elderly, who usually live alone or are alone when the crisis arrives. Carlos Guerreiro, a professor at the State University of Campinas (Unicamp), said that doctors may suspect epilepsy in elderly people from what they themselves report about what they felt before the crises, such as dizziness, fear, muscle pain or intense sweating, or after, such as memory loss, confusion and muscle pain. Another complication is that epilepsy among the elderly, may coexist with cardiovascular disease, chronic kidney disease, diabetes or dementia, and sometimes the drugs used against epilepsy may reduce the effect, for example, of anti-hypertension drugs. Because of the continuous aging of the population and the prospect of life expectancy being extended from the current 72.7 years to over 80 by 2030, he concluded, “We’re going to have more and more epilepsy in the elderly.”

The origins of epilepsy are also varied – gene defects, chromosomal abnormalities, metabolic disorders and brain tumors or injuries. “In the central nervous system there’s a complex molecular game,” said Marina Bentivoglio, from the University of Verona, Italy. Because of the interaction between neurotransmitters, hormones and proteins they continually stimulate the proliferation, migration and differentiation of nerve cells, “This environment is changing all the time,” she said.

Another possibility: epilepsy, Alzheimer’s disease, multiple sclerosis and other neurological disorders can result from inflammation in the glial cells that surround neurons. Ten times more numerous than neurons, for decades the idea about glial cells was that they just served as support for and cohesion of the tissue of the central nervous system. Now they have been shown to be relevant for the transmission of electrical stimuli, facilitating the connections between neurons, and for fighting infections and damage to the nervous system. Today it is clear that lesions in the glial cells can disrupt the functioning of neurons or lead to their death. “Glia are currently ‘in fashion'”, said Scorza, in view of the existing indications that physical exercise and Omega-3 seem to be able to keep the glial cells running smoothly.

The projects
1. Effect of physical exercise on cerebral plasticity in rats under development (nº 2004/10820-6); Modality Regular Research Awards; Coordinator Ricardo Mario Arida – Unifesp; Investment R$ 91,813.39 (FAPESP)
2. The role of Omega-3 in the model of pilocarpine-induced epilepsy (nº 2007/00763-3); Modality Regular Research Awards; Coordinator Fúlvio Alexandre Scorza – Unifesp; Investment R$ 48,103.59 (FAPESP)

Scientific articles
CAMILO, F. et al. Avaliação do esforço físico intenso em indivíduos com epilepsia do lobo temporal. Arquivos de Neuro­psiquiatria. 67(4), p.1.007-12. 2009.
SCORZA, F. A. et al. Benefits of sunlight: vitamin D deficiency might increase the risk of sudden unexpected death in epilepsy. Medical Hypotheses. 74(1), p. 158-61. 2010.