Roberta M. Cysneiros

The other side of the coin: Beneficiary effect of omega-3 fatty acids in sudden unexpected death in epilepsy.

The epilepsies are the most common serious neurological condition. People with epilepsy have a two- to threefold increased risk of dying prematurely than those without epilepsy, and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). The exact pathophysiological causes of SUDEP remain unknown, but it is very probable that cardiac arrhythmia during and between seizures plays a potential role. Although the pharmacological treatments available for the epilepsies have expanded, antiepileptic drugs are still limited in clinical efficacy. In this regard, several factors such as genetic, environmental, and social can contribute to the inefficacy of therapeutic outcome in patients with epilepsy. Among these factors, nutritional aspects, that is, omega-3 fatty acid deficiency, have an interesting role in this scenario. Animal and clinical studies have demonstrated that omega-3 fatty acids may be useful in the prevention and treatment of epilepsy. Moreover, as omega-3 fatty acids per se have been shown to reduce cardiac arrhythmias and sudden cardiac deaths, it has been proposed that omega-3 fatty acid supplementation in patients with refractory seizures may reduce seizures and seizure-associated cardiac arrhythmias and, hence, SUDEP. Given their relative safety and general health benefits, our update article summarizes the knowledge of the role of dietary omega-3 fatty acids in epilepsy.

Sudden unexpected death in epilepsy: From the lab to the clinic setting

Sudden unexpected death in epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in a patient with epilepsy. Sudden unexpected death in epilepsy is probably the most common cause of epilepsy-related deaths. Many predisposing and initiating factors may coexist and contribute to SUDEP, but the mechanisms are poorly understood. Cardiac and respiratory deregulation seems to have a major role in SUDEP. Here, we review several advances in understanding the mechanisms involved in SUDEP.

Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids

Studies have provided evidence of the important effects of omega-3 fatty acid on the brain in neurological conditions, including epilepsy. Previous data have indicated that omega-3 fatty acids lead to prevention of status epilepticus-associated neuropathological changes in the hippocampal formation of rats with epilepsy. Omega-3 fatty acid supplementation has resulted in extensive preservation of GABAergic cells in animals with epilepsy. This study investigated the interplay of these effects with neurogenesis and brain-derived neurotrophic factor (BDNF). The results clearly showed a positive effect of long-term omega-3 fatty acid supplementation on brain plasticity in animals with epilepsy. Enhanced hippocampal neurogenesis and BDNF levels and preservation of interneurons expressing parvalbumin were observed. Parvalbumin-positive cells were identified as surviving instead of newly formed cells. Additional investigations are needed to determine the electrophysiological properties of the newly formed cells and to clarify whether the effects of omega-3 fatty acids on brain plasticity are accompanied by functional gain in animals with epilepsy.

Mothers of children with cerebral palsy with or without epilepsy: a quality of life perspective

Purpose. Disability in a child affects not only the childs life but also the familys life. The aim of our study is to verify the quality of life (QOL) of mothers of disabled children with cerebral palsy (CP) with epilepsy compared with non-epilepsy children evaluated in a Brazilian center. Methods. Thirty mothers of disabled children participated in the study. The control group comprised of 18 healthy mothers of children without disabilities. All mothers agreed to participate in the study. They completed the evaluation forms of the SF-36 health survey, a well-documented, self-administered QOL scoring system. Results. The results of our study support the premise that mothers of children with CP, as a group, have poorer QOL than mothers of not disabled children. Conclusions. We also observed that mothers of children with CP and epilepsy have poorer QOL than mothers of children with CP without epilepsy.

Positive impact of omega-3 fatty acid supplementation in a dog with drug-resistant epilepsy: a case study.

Epilepsy is the most common neurological disorder in both dogs and humans. Although the pharmacological options for treatment of epilepsies have increased, it has been reported that two-thirds of dogs with epilepsy are refractory to antiepileptic drug therapy. To our knowledge, there are no experimental studies in the literature that show an effect of omega-3 supplementation on epilepsy in dogs. Our case study describes the effectiveness of daily intake of a moderate amount of fish oil in a case of canine epilepsy.

Physical exercise in rats with epilepsy is protective against seizures: evidence of animal studies

People with epilepsy have been discouraged from participating in physical activity due to the fear that it will exacerbate seizures. Clinical and animal studies indicate a reduction of seizure frequency as well as decrease susceptibility to subsequently evoked seizures after an exercise program. Analyses from experimental studies of animals with epilepsy submitted to physical training programs were performed. In all studies the physical training was able to reduce the number of spontaneous seizures in rats with epilepsy. Seizure occurrence during exercise was relatively absent in the majority of studies. No death was found in animals with epilepsy during 1680 h of exercise. Based on these results it is plausible encouraging persons with epilepsy to non-pharmacological treatments and preventative measures such as physical exercise.

Fish oil attenuates methylmalonate-induced seizures

Methylmalonic acidemias are inherited metabolic disorders characterized by methylmalonate (MMA) accumulation and neurological dysfunction, including seizures. Dietary fatty acids are known as an important energy source and reduce seizure activity in selected acute animal models. This study investigated whether chronic treatment with fish oil or with oleic acid attenuates MMA-induced seizures and whether maintenance of Na(+),K(+)-ATPase activity was involved in such an effect. Adult male Wistar rats were given fish oil (85 mg/kg), oleic acid (85 mg/kg) or vehicle (0.42% aqueous Cremophor EL™, 4 mL/kg/body weight/day), p.o., for 75 days. On the 73th day a cannula was implanted in the right lateral ventricle with electrodes over the parietal cortex for EEG recording. On the 76th day the animals were injected with NaCl (2.5 μmol/2.5 μL, i.c.v.), or with MMA (2.5 μmol/2.5 μL, i.c.v.), and seizure activity was measured by electroencephagraphic (EEG) recording with concomitant behavior monitoring. The effect of prostaglandin E2 (PGE2) on Na(+),K(+)-ATPase activity of slices of cerebral cortex from NaCl-injected animals was determined. Fish oil increased the latency to MMA-induced tonic-clonic seizures, reduced the mean amplitude of ictal EEG recordings, and prevented PGE2-induced decrease of Na(+),K(+)-ATPase activity in cortical slices in vitro. Oleic acid decreased mean amplitude of ictal EEG recordings. The results support that fish oil decreases MMA-induced seizures. The decreased sensitivity of Na(+),K(+)-ATPase to the inhibitory effect of PGE2 in fish oil-treated animals may be related to the currently reported anticonvulsant activity.

Fish consumption, contaminants and sudden unexpected death in epilepsy: many more benefits than risks

People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.

Adult hippocampal neurogenesis and sudden unexpected death in epilepsy: Reality or just an attractive history?

Neurogenesis persists throughout life in the adult mammalian dentate gyrus and is regulated by several environmental, physiological, and molecular factors. Seizure activity also influences dentate granule cell neurogenesis. In these lines, studies of neurogenesis have demonstrated the presence of hilar-ectopic dentate granule cells after status epilepticus induced experimentally and that these cells are migrate aberrantly, abnormally integrated and hyperexcitable, contributing with this to seizure generation and/or propagation. As we know, epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. Based on these facts, in this paper we postulate that aberrant neurogenesis could influence negatively the cardiovascular system of the patient with epilepsy leading to cardiac abnormalities and hence SUDEP.

The stability of fish populations: how changes in the environment may affect people with epilepsy

The association between fish consumption and low rates of cardiovascular disease was studied nearly 40 years ago in the seafood diets consumed by Greenland Eskimos, Alaskan Natives and Japanese people residing in fishing villages.[1 Omega‐3 fatty acids (from fatty fish in the human diet) also appear effective on the functioning of the brain.2 Furthermore, it is interesting to note that, of all organs in the human body excluding adipose tissue, the central nervous system (CNS) has the highest lipid content; for instance, approximately 50% of fatty acids are polyunsaturated in the gray matter, a third of which are of the omega‐3 family, and are thus dietary in origin.2 In humans, the intake of omega‐3 fatty acids, commonly found in fish and fish oil, not only contributes to CNS development but also plays a role in achieving optimal health and in the protection against certain adult CNS diseases.2 With respect to CNS disorders, epilepsy occupies a prominent place in this scenario. Epilepsy is considered one of the most prevalent neurological conditions and approximately 50 million people worldwide are affected.3 From an epidemiological point of view, it must be acknowledged that most patients who develop epilepsy will go into remission, whilst remaining patients continue to have seizures and are refractory to treatment with the currently available therapies.4 Despite great advances in pharmacological treatment of epilepsy, anti‐epileptic drugs are not completely effective in controlling seizures of patients with epilepsy. As such, dietary management, with particular emphasis on omega‐3 fatty acids, is often tried by neurologists to control seizures in patients with epilepsy. The results of the first randomized trial of omega‐3 fatty acids supplementation in patients with chronic epilepsy were encouraging, demonstrating a transient effect on seizure control.5 Although these results did not totally confirm that omega‐3 fatty acids supplementation reduced the frequency of epileptic seizures in patients with refractory epilepsy, they established the safety of omega‐3 fatty acids supplementation in people with epilepsy.5 From an experimental point of view, our research group was the first to demonstrate that chronic treatment with omega‐3 promotes neuroprotection and positive plastic changes in the brain of rats with epilepsy.6 Considering the potential health benefits of fish consumption and the positive effects of omega‐3 supplementation in various CNS diseases, an intriguing question arose: should neuroscientists be concerned with the changes in the structure and abundance of fish fauna? Yes, they should be. Why? Firstly, it is widely accepted that there is a severe problem with future global food supply and security.7 Fish consumption has increased substantially and, for this reason, several fish populations are being devastated and unable to produce their maximum sustainable yields.7 Unfortunately, illegal, unreported and unregulated (IUU) fishing contributes to overexploitation of fish stocks and is a hindrance to the recovery of fish populations and of the whole ecosystem.7 Furthermore, it is also important to note that IUU has a direct impact on annual economic benefits (