Premature Deaths in Persons with Seizure Disorders—Subtherapeutic Levels of Anticonvulsant Drugs in Postmortem Blood Specimens

Abstract

The purpose of this paper is to point out the possibility of death occurring prematurely in epileptics from apparently inadequate anticonvulsant therapy. Moreover, the information may be useful to the forensic pathologist faced with the “difficult autopsy” [1] where no definite cause of death is found. Toxicology is most useful in demonstrating deaths resulting from overdoses. However, subtherapeutic or negative anticonvulsant drug levels in a known epileptic may have equal usefulness in establishing a probable cause of death. The potential problem for the pathologist may be emphasized if he realizes there are approximately 1.7 million epileptics living in the United States today [2]. Rarely does the death of an epileptic make headlines in a major newspaper.

Intractable Seizures: Long‐Term Follow‐up After Prolonged Inpatient Treatment in an Epilepsy Unit

“…This cause of death was reported in epileptic patients at least as early as 1885 (Gowers, 1885;Anchisi, 1906). It has been suggested that epileptic patients sleep without pillows, especially if nocturnal seizures occur (Bridge, 1949;Langmore and Wilson, 1970;Bowerman et al, 1978). These patients often have low levels of anticonvulsant drugs at autopsy (Bowerman et al, 1978;Terrance et al, 1981).…”

Sudden Unexplained Death and Injury in Epilepsy

“…Patients were typically young males, had GTC seizures, and had low or absent antiepileptic drug (AED) levels. Other studies (21,22) have also suggested that low AED levels may be a risk factor for SUDEP. A retrospective study by Leestma et al (18) reported that most patients with epilepsy whose deaths were sudden and unexplained were black males or had abused alcohol.…”

“…Early studies (12)(13)(14)(15) of causes of death in patients with epilepsy identified a group of patients who died for no apparent reason. Later studies (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) of patients with epilepsy who died suddenly and unexpectedly reported certain risk factors and provided estimates of incidence of SUDEP. More recently, population-based studies (28) have determined SUDEP rates in the general epilepsy population, whereas others (29) have attempted to identify potential risk factors for SUDEP.…”

Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep

“…12 A substantial propor-tion of deaths in populations with intractable seizures is attributable to sudden unexpected death in epilepsy (SUDEP). [19][20][21][22] It is also unresolved whether the importance of AED polytherapy and frequent changes merely reflect seizure severity or whether AED withdrawal incites more severe seizures or has deleterious effects on other factors such as autonomic cardiac regulation and arrhythmogenesis. [13][14][15][16] Descriptive risk factors for SUDEP, although not all confirmed in case-control studies, have included youth, generalized tonic-clonic seizures, nocturnal seizures, unwitnessed seizures, structural substrate on neuropathology, remote symptomatic epilepsy, male gender, and noncompliant or abrupt drug withdrawal.…”