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Abstract
Epilepsy is the most common chronic disabling condition of the nervous system, affecting up to 400 000 people in the United Kingdom. Overall mortality in epilepsy is increased up to three-fold compared with the general population.
The risk of death for a person with epilepsy is increased compared with the risk for the general population.
The causes of death among people with epilepsy may be ;(1) completely independent of the epilepsy,(2) related to the underlying etiology of epilepsy or to co morbidities , (3) caused by the treatment, or (4) directly (e.g., status epilepticus and sudden unexpected death in epilepsy ”SUDEP”) or indirectly caused by seizures (e.g., accidents). Fatalities caused by the treatment are rare.
Over the last 20 years, there has been growing interest in SUDEP.
This is considered to be the most common epilepsy-related cause of premature death.
SUDEP is often seen in people who continue to have uncontrollable, drug-resistant seizures. Usually, the subjects are found dead in bed in the morning without any clear pathological cause or behavioral indications. The standard mortality ratio (SMR), which measures mortality relative to the general population, is two to six times higher in people with epilepsy.
14–50% of these deaths appear to be SUDEP related. Thus, the incidence of unexpected, unexplained death is up to 40 times higher in people with epilepsy than in the general population, with a reported prevalence of 0.1 to 9.3 per 1000 persons per year. Thus, we considered that epilepsy is associated with a two to three fold increase in mortality compared to the general population, and SUDEP is the most important direct epilepsy-related cause of death.
Status epilepticus is a true medical emergency, with substantial morbidity and mortality. The prognosis in patients who have SE depends not only on the underlying disease but on successful treatment of the seizures from clinical and electrographic perspectives. In several large patient series, the overall 30-day mortality rate of patients who had generalized convulsive status epilepticus (GCSE) ranged from 19% to 27%. Mortality was higher in those patients who remained in GCSE for an hour or longer.
The International Classification of Epileptic Seizures, along with a general consensus, described SE as any seizure lasting more than 30 minutes or intermittent seizures from which the patient did not regain consciousness lasting for more than 30 minutes. The rationale for choosing 30 minutes was based on the minimum duration thought to result in neuronal injury in animal models.
There are two major types of SE based exclusively on seizure semiology. The first type is generalized SE, which is subdivided into two groups: (1) generalized convulsive SE (GCSE), which is tonic-clonic SE or grand mal SE, tonic SE, clonic SE, or myoclonic SE; and (2) non convulsive generalized SE, including petit mal status. The second type is partial SE, which is subdivided into two groups: simple partial SE (eg, somatomotor or aphasic SE) and complex partial SE.
The burden of morbidity and mortality due to epilepsy is attributable not only to the occurrence of seizures, but also to the concomitant occurrence of several ‘‘clinically distinct conditions’’ known as comorbidity.
Mood disorders (depression and bipolar disorder) and other psychiatric diseases (e.g., schizophrenia-like psychosis), personality disorders (borderline personality disorder), substance abuse, self-destructive-behavior, previous suicide attempts, and critical life events are established risk factors for suicide and suicide attempts.
Frontal lobe dysfunction may be related to a deficit in serotonergic transmission, which could predispose to depression and suicidal behavior.
Suicide is more frequent in patients with epilepsy than in the general population, it is concluded that the suicide rate in a given cohort of individuals with a diagnosis of epilepsy was not determined by factors influencing the suicide rate in the general population from which the particular cohort originated.
In comparison to some of the well-known associations, co morbidity due to cancer has received little attention), Cancer is the second most frequent cause of death worldwide. Naturally, it can complicate several chronic medical conditions, including epilepsy, fuelling concerns about the cancer risk or lack thereof associated with the underlying disorder. Pertinent to this cancer risk is the carcinogenicity of drugs used over long periods of time to treat these disorders, particularly so because drug exposure is a potentially avoidable risk. Accordingly, testing for carcinogenicity is crucial in the evaluation of drug safety.
The potential for AEDs to be carcinogenic was investigated in experimental, epidemiological and clinical research, early experimental studies showed that Phenobarbital could facilitate liver tumours, and that phenytoin administration resulted in both lymphoid and liver tumours in rodents.
Carcinogenicity studies for AEDs may be carried out in samples of people with either cancer or epilepsy. Studies in samples of persons with cancer use a retrospective case–control design. Though theoretically appealing, these are rarely feasible, being complicated by recall bias and the fact that epilepsy history is often not mentioned in records of cancer registries or death certificates of people dying of cancer.
People with epilepsy may drown when suffering seizure during swimming or bathing. The US study of drownings and near-drownings in children found that inadequate supervision was frequently associated with submersions. There may be a slight reduction in the risk of death by drowning over time .The data from the most recent studies, however, providing an SMR of 15.6, confirm that deaths by drowning still occur far in excess of those in the general population, emphasizing the importance of educating people with epilepsy and their carers of the risks of drowning.
Death by drowning can be seen to be a consistently important cause of death in people with epilepsy. Drowning appears to cause fewer deaths than, for example, SUDEP, but it should be easier to prevent, as the cause is known and understood. It is imperative that people with epilepsy and their families are appropriately counseled and the risk associated with these activities is explained to them. Showering should be preferred over bathing when possible. Adequate seizure control and taking of precautions should be established for all patients in order to avoid more deaths.
Little is known about disparities in injury mortality for people with epilepsy/seizures and whether differences exist in the place of injury death (i.e., death occurring in the prehospital phase vs death occurring after reaching a hospital). The identification of disparities in location of injury death is an important first step in understanding potential contributing factors such as access to emergency medical services, potential discrimination and/or bias among health care professionals, and prehospital medical control protocols and practices.
Over three fold increased risk of death associated with AED non adherence relative to adherent behavior, even after controlling for potential confounders. AED non adherence was also associated with other serious clinical events, including an 86% higher incidence of hospitalizations and a 50% higher incidence of ED visits. Fractures and injuries from motor vehicle accidents (MVA) were also significantly more common during periods of non adherence.
Non adherence is associated with severe clinical consequences, including increased risk of death. In order to better protect patients, it is vital for us to understand what factors drive non adherence, and for clinicians, payers, and drug innovators to use this knowledge to promote treatment strategies for epilepsy that offer increased likelihood of adherence.