Epilepsy is a neurological and a systemic disorder.

The basic pathophysiology of epilepsy is still not fully understood. Epidemiological evidence for epilepsy seems to suggest that it may not only be the propensity for seizures to occur. The high prevalence of comorbidity and the finding that premature mortality is still increased in those who are in long-term remission, suggest that there is a systemic component to the condition.

An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy.

Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues.

Can natural ways to stimulate the vagus nerve improve seizure control?

The vagus nerve (VN) is the longest cranial nerve, innervating the neck, thorax and abdomen, with afferent fibers transmitting a range of interoceptive stimuli and efferent fibres to somatic structures and autonomic preganglions. Over the last few decades, electrical stimulation of the VN using implanted devices (VNS) has been developed leading to its approval for the treatment of epilepsy and depression. More recently, non-invasive devices to stimulation the VN have been developed.

Rationale for using intermittent calorie restriction as a dietary treatment for drug resistant epilepsy.

There has been resurgence in the use of dietary treatment, principally the classical ketogenic diet and its variants, for people with epilepsy. These diets generally require significant medical and dietician support. An effective but less restrictive dietary regimen is likely to be more acceptable and more widely used.

Can magnesium supplementation reduce seizures in people with epilepsy? A hypothesis.

Magnesium is required for over 300 enzyme systems and is critical for many cellular functions including oxidative phosphorylation, glycolysis, DNA transcription and protein synthesis. Studies suggest that the modern Western diet and lifestyle may lead to magnesium deficiency, and this appears to be associated with a wide range of medical conditions. Magnesium deficiency decreases seizure thresholds in animal models of epilepsy and indeed low magnesium concentration in the perfusate is a common method of generating spontaneous epileptiform discharges from rat hippocampal slices.

Non-randomized open trial of eicosapentaenoic acid (EPA), an omega-3 fatty acid, in ten people with chronic epilepsy.

This is a non-randomized open assessment of eicosapentaenoic acid (EPA) supplementation in ten people (five males) with refractory focal seizures. Each received 1000 mg of EPA daily for 3 months. Six people had fewer seizures during the supplementation period compared with baseline (range 12 to 59% reduction) and one other person had markedly reduced seizure severity.

Impaired mitochondrial energy production: the basis of pharmacoresistance in epilepsy.

Twenty to thirty percent of people who develop epilepsy continue to have seizures despite antiepileptic drug (AED) treatment. The introduction of many new AEDs in the last two decades does not appear to have reduced substantially the proportion of people who are pharmacoresistant and continue to have seizures. Currently there are two main mechanisms suggested for pharmacoresistance in people with epilepsy: the transporter and target hypothesis.

The long-term retention of zonisamide in a large cohort of people with epilepsy at a tertiary referral centre.

Zonisamide (ZNS) is an antiepileptic drug (AED) with multiple putative mechanisms of action. It is chemically unrelated to other AEDs. It has been available in Japan since 1989 but was only licensed in Europe in 2005.

Effects of AEDs on biomarkers in people with epilepsy: CRP, HbA1c and eGFR.

The standardised mortality ratio in people with epilepsy is raised to between 2 and 3 compared with the general population. Some biomarker levels, including higher C-reactive protein (CRP), higher glycosylated haemoglobin (HbA1c) and lower estimated glomerular filtration rate (eGFR), are associated with an increase risk of premature mortality. These biomarkers were measured in 125 people with refractory epilepsy to estimate the potential effect of antiepileptic drug (AED) use on these markers.

Can slow breathing exercises improve seizure control in people with refractory epilepsy? A hypothesis.

Studies on various medical conditions have shown that poor health is associated with lower parasympathetic tone. People with epilepsy appear to have decreased parasympathetic tone, with a greater decrease in those with intractable seizures than in those with well-controlled epilepsy. Slow breathing exercises have been shown to increase parasympathetic tone in healthy volunteers.

The long-term retention of pregabalin in a large cohort of patients with epilepsy at a tertiary referral centre.

Pregabalin (PGB) is a new antiepileptic drug (AED) which is a structural, non-functional analogue of gamma-aminobutyric acid. It acts at presynaptic calcium channels to modulate neurotransmitter release in the CNS. While the efficacy and tolerability of PGB have been demonstrated in several randomised controlled trials, few studies have addressed long-term outcome in large groups of patients.

Erythrocyte and plasma fatty acid profiles in patients with epilepsy: does carbamazepine affect omega-3 fatty acid concentrations?

Fatty acids (FAs) determine membrane properties and may affect cardiac and neuronal function. In this study, FA profiles were determined in 56 patients with epilepsy who participated in a 12-week double-blind randomized trial of omega-3 FA supplementation (1 g eicosapentaenoic acid and 0.7 g docosahexaenoic acid daily).

Mortality and morbidity rates are increased in people with epilepsy: is stress part of the equation?

People with epilepsy (PWE), particularly those with more severe seizures, are at risk of premature death. The contribution of deaths unrelated to epilepsy to this risk is likely to be significant. Recent studies indicate that comorbid conditions are similarly increased in PWE.

Low-grade chronic metabolic acidosis is a contributory mechanism in the development of chronic epilepsy.

In most people with epilepsy, the condition is readily controlled, but 20-30% develop chronic epilepsy. An estimated 80,000 patients with epilepsy require ongoing specialist care in the United Kingdom. Nutrition may be a factor in the development of chronic epilepsy.

Omega-3 fatty acid supplementation in patients with chronic epilepsy: a randomized trial.

Animal studies and a preliminary clinical observation suggest that nutritional supplementation with long chain omega-3 fatty acids (omega-3 FAs) may be useful in the nonpharmacological treatment of patients with epilepsy. Omega-3 FAs increase seizure thresholds, and lower inflammatory mediators, which are increased in patients with epilepsy. In this first randomized, placebo-controlled parallel group trial of omega-3 FA supplementation with 1 g eicosapentaenoic acid (EPA) and 0.

Is omega-3 fatty acid deficiency a factor contributing to refractory seizures and SUDEP? A hypothesis.

Epilepsy, the commonest serious neurological condition, is associated with an increased risk in premature deaths, including an estimated 500 sudden unexpected deaths (SUDEP) per year in the UK. In some patients seizures are associated with cardiac arrhythmias, which are thought to be a major factor in SUDEP. Omega-3 fatty acids have been shown to reduce cardiac arrhythmias in animal studies and to reduce sudden cardiac deaths, thought to be due to cardiac arrhythmias, in both healthy subjects and in those who have had one myocardial infarction.