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Zoonotic and vector-borne parasites are important preventable risk factors for epilepsy. Three parasitic infections — cerebral malaria, Taenia solium cysticercosis and onchocerciasis — have an established association with epilepsy. Parasitoses are widely prevalent in low-income and middle-income countries, which are home to 80% of the people with epilepsy in the world. Once a parasitic infection has taken hold in the brain, therapeutic measures do not seem to influence the development of epilepsy in the long term. Consequently, strategies to control, eliminate and eradicate parasites represent the most feasible way to reduce the epilepsy burden at present. The elucidation of immune mechanisms underpinning the parasitic infections, some of which are parasite-specific, opens up new therapeutic possibilities. In this Review, we explore the pathophysiological basis of the link between parasitic infections and epilepsy, and we consider preventive and therapeutic approaches to reduce the burden of epilepsy attributable to parasitic disorders. We conclude that a concerted approach involving medical, veterinary, parasitological and ecological experts, backed by robust political support and sustainable funding, is the key to reducing this burden. Zoonotic and vector-borne parasites are important preventable risk factors for epilepsy. The authors explore the pathophysiological basis of the link between parasitic infections and epilepsy and consider preventive and therapeutic approaches to reduce the epilepsy burden associated with parasitic disorders.

Purpose of Review Sudden Unexpected Death in Epilepsy (SUDEP) is the commonest cause of epilepsy-related premature mortality in people with chronic epilepsy. It is the most devastating epilepsy outcome. We describe and discuss risk factors and possible pathophysiological mechanisms to elucidate possible preventative strategies to avert SUDEP. Recent Findings Sudden death accounts for a significant proportion of premature mortality in people with epilepsy compared to the general population. Unmodifiable risk factors include a history of neurologic insult, younger age of seizure-onset, longer epilepsy duration, a history of convulsions, symptomatic epilepsy, intellectual disability, and non-ambulatory status. Modifiable risk factors include the presence of convulsive seizures, increased seizure frequency, timely and appropriate use of antiseizure medications, polytherapy, alcoholism, and supervision while sleeping. Pathophysiology is unclear, but several possible mechanisms such as direct alteration of cardiorespiratory function, pulmonary impairment, electrocerebral shutdown, adenosine dysfunction, and genetic susceptibility suggested. Summary Methods to prevent SUDEP include increasing awareness of SUDEP, augmenting knowledge of unmodifiable risk factors, obtaining full seizure remission, addressing lifestyle factors such as supervision and prone positioning, and enacting protocols to increase the detection of and intervention for SUDEP. Further studies are required to characterize precisely and comprehensively SUDEP risk factors and pathophysiological drivers and develop evidence-based algorithms to minimize SUDEP in people with epilepsy.

A recent longitudinal study indicates that the incidence of new-onset epilepsy has remained stable in children and young adults but has increased in elderly individuals over the past 40 years. Rather than signalling a failure to prevent epilepsy, however, this phenomenon might be attributable to the comorbidities of epilepsy.

Little published information exists about the management of dental treatment procedures for people with epilepsy who, despite their medication, continue to have seizures. This paper draws on relevant literature in neurology and anaesthetics to provide a multi-speciality consensus on methods of assessment and adjunctive treatment options in order to manage the risk of a clinically significant seizure occurring during a procedure. It aims to enhance current guidelines and practice in the provision of specialist care for this diverse group.

Suicide is an important cause of premature death, and people with epilepsy are thought to be at increased risk for suicide. Antiepileptic drugs (AEDs) continue to be the mainstay of epilepsy treatment, but the benefits of seizure control must be balanced with their psychotropic potential. In recent years, suicidality has been recognized as a complication of several groups of drugs and, most recently, AEDs were implicated in an alert by the US Food and Drug Administration. The risk of suicidal ideation and behavior as side effects of AED treatment is low, and in people with epilepsy, such a risk must be balanced against the risk of not treating the seizures.

Suicide is an important cause of premature death. In the general population, most people who commit suicide have a psychiatric problem at the time. People with epilepsy are thought to be at increased risk from suicide and suicidality (suicidal ideation or behaviour). Standardized mortality ratios estimated for suicide in people with epilepsy are usually between 3 and 5. Risk factors for suicide in people with epilepsy have been suggested, including early age of onset of seizures, temporal lobe epilepsy, severe seizures and recent control of seizures. Psychiatric co-morbidity also seems to be an important factor in people with epilepsy who commit suicide. In recent years, suicidality has been recognized as a complication of several groups of drugs and, most recently, antiepileptic drugs (AEDs) have been implicated. The US FDA performed a meta-analysis of 199 placebo-controlled studies of 11 AEDs used for seizure control, psychiatric or 'other' indications. There were four completed suicides in those taking AEDs and none in those taking placebo. The odds ratio for suicidal behaviour or ideation was 1.8 (95% CI 1.24, 2.66), suggesting that people taking AEDs are more at risk than those taking placebo. The odds ratio was significantly raised for people taking AEDs for epilepsy, but not for the other indications. AEDs may affect mood by means of several mechanisms. In people with epilepsy, however, the concept of forced normalization (or alternative psychosis) may also play a part. In this situation, control of seizures (by AEDs or epilepsy surgery) may alternate with psychotic features or, less commonly, depression, although this is not fully understood. The risk of suicidal ideation and behaviour as adverse effects of AED treatment, although increased, seems low. As a result of the FDA's alert clinicians are supposed to inform patients and their families of this increased risk but it is important to place it in a proper perspective. Some people with epilepsy are more likely to develop psychiatric adverse effects with any AEDs, and these people should be followed closely whenever a new AED is introduced. Nonetheless, in people with epilepsy the risk of suicidality associated with AEDs needs to be balanced against the risk of not treating the seizures. In fact, the risk of stopping AEDs or refusing to start AEDs for the control of a seizure disorder may be significantly worse and may result in serious harm, including death of the patient.

Individuals with epilepsy have a mortality rate 2 to 3 times that of the general population, attributable both to any underlying disease that may be causing epilepsy and to the epilepsy itself. The commonest category of seizure-related death is sudden unexpected death in epilepsy (SUDEP). The epidemiology of SUDEP has been extensively studied and a number of such studies have taken anticonvulsant drug usage as an indicator of epilepsy, although obviously this may lead to inaccuracies. Epidemiological work has also yielded information about possible risk factors for SUDEP. At present there is no evidence that any particular anticonvulsant influences this risk, although there are anecdotal reports of sinus arrest and arrhythmias occurring in individuals receiving carbamazepine. A recent case-control study found that the risk of SUDEP increased with increasing number of concomitant anticonvulsants. In many cases of SUDEP, subtherapeutic anticonvulsant concentrations have been found at postmortem which may reflect noncompliance with medication, although the relationship between ante- and postmortem drug concentrations is unclear. The mechanism of SUDEP is unknown, although a possible role for anticonvulsants in its aetiology must be considered. Some anticonvulsants, by blocking sodium channels, have a direct effect on cardiac conduction, but studies examining the association between anticonvulsants and cardiac arrhythmia are lacking. As there is evidence to suggest an association between seizures and sudden death, the judicious use of anticonvulsants in optimising seizure control may be important in the prevention of these deaths.

Epilepsy is an important health problem throughout the world. In order to best manage epilepsy within a population, its epidemiological profile should be established. Epidemiological studies have shown that epilepsy is a very common, chronic condition that particularly affects the young and those in developing countries. Although the reported rates vary widely, the annual incidence rate of epilepsy is estimated to be approximately 40 to 70 per 100 000 population, and the prevalence is estimated to be approximately 4 to 10 per 1000 population.

Epilepsy is one of the most common neurological disorders. Even though existing antiepileptic drugs can render 80% of newly diagnosed patients seizure free, a significant number of patients have chronic intractable epilepsy causing disability with considerable socioeconomic implications. There is, therefore, a need for more potent and effective antiepileptic drugs and drugs with fewer adverse effects, particularly CNS effects. Drugs for the treatment of partial seizures are particularly needed. With major advances in our understanding of the basic neuropathology, neuropharmacology and neurophysiology of epilepsy, numerous candidate novel antiepileptic drugs have been developed in recent years. This review comparatively evaluates the pharmacokinetics, efficacy and adverse effects of 12 new antiepileptic drugs namely vigabatrin, lamotrigine, gabapentin, oxcarbazepine, felbamate, tiagabine, eterobarb, zonisamide, remacemide, stiripentol, topiramate and levetiracetam (ucb-L059). Of the 12 drugs, vigabatrin, lamotrigine and gabapentin have recently been marketed in the UK. Five of these new drugs have known mechanisms of action (vigabatrin, lamotrigine, tiagabine, oxcarbazepine and eterobarb), which may provide for a more rational approach to the treatment of epilepsy. Oxcarbazepine, remacemide and eterobarb are prodrugs. Vigabatrin, gabapentin and topiramate are more promising on the basis of their pharmacokinetic characteristics in that they are excreted mainly unchanged in urine and not susceptible to significant pharmacokinetic interactions. In contrast, lamotrigine, felbamate and stiripentol exhibit significant drug interactions. Essentially, all the drugs are effective in partial or secondarily generalised seizures and are effective to varying degrees in other seizure types. Particularly welcome is the possible effectiveness of zonisamide in myoclonus and felbamate in Lennox-Gastaut syndrome. In relation to adverse effects, CNS effects are observed with all drugs, however, gabapentin, remacemide and levetiracetam appear to exhibit least. There is also the possibility of rational duotherapy, using drugs with known mechanisms of action, as an additional therapeutic approach. The efficacy of these 12 antiepileptic drug occurs despite the fact that candidate antiepileptic drugs are evaluated under highly unfavourable conditions, namely as add-on therapy in patients refractory to drug management and with high seizure frequency. Thus, whilst candidate drugs which do become licensed are an advance in that they are effective and/or are associated with less adverse effects than currently available antiepileptic drugs in these patients, it is possible that these drugs may exhibit even more improved risk-benefit ratios when used in normal clinical practice.