Death from seizures induced by chronic alcohol abuse Does it exist?

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1 Seizure (2007) 16, REVIEW Death from seizures induced by chronic alcohol abuse Does it exist? S. Christoffersen * Institute of Forensic Medicine, University of Southern Denmark, Odense, Denmark Received 30 August 2006; received in revised form 29 January 2007; accepted 20 February 2007 KEYWORDS Seizure; Death; Chronic alcohol abuse Summary In a forensic setting, deaths due to seizures, either epileptic or other, present a well-known problem. Cause of death is rarely established on the basis of physical evidence, but on circumstantial evidence such as tongue biting or discharge of urine or faeces. Seizures have several different aetiologies, but in police reports a person known to have seizures is most likely to be reported as suffering from epilepsy. It is a well-known fact that alcoholics have seizures either due to alcohol-induced epilepsy or due to withdrawal from drinking. It also seems to be generally accepted that alcoholics may die from these seizures. A literature study was performed of deaths due to alcohol-induced seizures, either during withdrawal or as late-onset seizures where the aetiology was established as long time alcohol abuse and a necropsy had shown no other possible cause of death than a seizure. Results: It was not possible to find any well-documented cases. It is, however, difficult to compare cases in the literature, as there is no generally accepted classification or nomenclature of seizures related to alcohol abuse. # 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. Contents Introduction Materials and methods Results Discussion Conclusion References * Correspondence address: Retsmedicinsk Institut, J.B. Winsløws Vej 17, 5000 Odense C, Denmark. Tel.: ; fax: address: schristoffersen@health.sdu.dk. Introduction In a forensic setting, deaths due to seizures, either epileptic or other, present a well-known problem /$ see front matter # 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi: /j.seizure

2 380 S. Christoffersen Cause of death may be established due to nonspecific evidence such as a history of seizures, the circumstances under which the deceased was found, discharge of urine or faeces, tongue biting or perhaps subtherapeutic levels of anti-convulsive medication in blood. The most common necropsy findings are non-specific such as pulmonary oedema and/or congestion 1 5 which is a very common finding (38% of all necropsies at this institute from 1995 to 2004). Seizures may have several different aetiologies other than epilepsy such as infections, metabolic abnormalities, systemic diseases, alcohol and/ or drug withdrawal or other toxic exposure, etc. 6 Epileptics have an increased risk of dying, both from epilepsy and underlying causes A number of deaths are sudden unexpected death in epilepsy (SUDEP) where no cause of death is found at necropsy. Some of those are related to alcohol or are cases where the deceased previously have been admitted to hospital because of alcohol abuse, ranging from very few cases to 38% in different studies. 1,2,15,16 It is a well-known fact that alcoholics have seizures either due to alcohol-induced epilepsy or during withdrawal from drinking Alcohol abuse and withdrawal seizures are associated with generalised tonic clonic seizures (GTCS), 19,20,21,26 28 and alcoholics might progress into status epilepticus (SE) from their withdrawal seizures In epileptics, SE from GTCS is correlated with higher mortality 28 compared to other types. Therefore it seems likely that alcoholics may die from alcoholinduced SE. This seems to be generally accepted. But do the seizures due to chronic alcohol abuse actually cause death? Materials and methods In this study, a literature search on epilepsy, seizures, alcohol, alcohol abuse, alcohol withdrawal seizures, mortality, death and any combination thereof was made using Pub.Med and SilverPlatter. Deaths due to seizures related to chronic alcohol abuse, either during withdrawal or as late-onset seizures, were investigated. Only seizures where (1) the aetiology was established as alcohol abuse (i.e. withdrawal seizures or late-onset seizures), (2) where a necropsy had been performed and (3) death had no other possible cause than seizure, were considered. To make sure that the seizures were due to long time alcohol abuse, anyone having idiopathic, symptomatic or post traumatic epilepsy or having any cause of death other than seizure verified by necropsy was excluded. Results Many publications relating to epilepsy, seizures, alcohol abuse, alcohol withdrawal and mortality can be found, but only a few of these address the aspects of this investigation. It seems likely that alcohol abuse in itself can lead to seizures in different ways, either during periods of alcohol withdrawal (complete abstinence or partial) 20 or as late-onset seizures 31 that may occur during drinking or any time after cessation. These seizures are thought to arise from the toxic effects of alcohol which over time will lower the alcoholic s seizure threshold due to upregulation of NMDA-receptors in neurons (kindling). 22,32 There is, however, not an agreement whether the decisive factor is the length of time of the alcohol abuse, the total alcohol consumption regardless of time, 33 amount of alcohol consumed daily 19 or the number of detoxifications/previous seizure episodes 21,24,34 as suggested in the alcohol withdrawal syndrome (AWS) theory. 27 Alcohol might also induce seizures directly or indirectly in other ways, by tricking known epilepsy, by causing head trauma, by acute intoxication, etc., but these were excluded from this investigation. Below a few selected studies are described: Alldredge and Lowenstein 26 found that of 249 SE patients admitted to the San Francisco General Hospital between 1977 and 1989, alcohol was the only identifiable precipitating cause of SE in 10.8%, and only one of these patients died. Cause of death was described as cardiopulmonary arrest as late as 8 days after being admitted to the hospital. Denison et al. 35 studied 97 deaths of known alcohol dependent males. They found that epileptic seizures may have contributed to deaths in seven so-called obscure deaths and were the cause of death in five cases. Of these five traumatic head injury or cerebral changes were found in three and pneumonia in one case. The last was seen with seizures the day before he was found dead in his room. Unfortunately, there is no information of whether a necropsy was performed on this person as the article only stated that these five deaths were all forensically examined. Pilke et al. 30 found three deaths in 82 cases of grand mal SE, 22 of the cases could be related to alcohol. None of these three deaths could be directly related to the seizures. One died from liver necrosis possibly as a result of phenytoin therapy, one from pneumonia and one from cerebral metastases.

3 Death from seizures induced by chronic alcohol abuse 381 Foy et al. 36 concluded that there is no mortality associated with alcohol withdrawal itself, as of 539 cases reported only two deaths during alcohol withdrawal, and both of these were admitted to hospital with severe respiratory failure, became delirious and developed irreversible respiratory failure following sedation. Copeland 37 reported 118 cases (113 necropsies), in five deaths alcohol was listed as either primary or contributory cause of death, with seizure disorder due to chronic alcoholism with or without trauma as cause of death. These may include cases with alcohol-induced epilepsy, but a detailed description was not done. Lewis et al. 38 conducted a 20-year follow-up study of predictors of mortality in 259 alcoholics and did not even mention seizures or epilepsy. Hansen and Simonsen 39 included 122 deaths in known alcoholics, where a necropsy was performed at a forensic institute. Three of these showed signs of a seizure, and epilepsy was stated as might be cause of death. There is, however, no information on necropsy findings or known type of epilepsy in the three cases which again means that it is not possible to assess whether the seizures were induced by alcohol-induced epilepsy or another form of epilepsy. Lykke 40 reported 206 deaths in an alcoholic clientele. In this group epilepsy was the predominantly known somatic disease, but still no deaths were attributed to epilepsy. Twenty-two deaths were categorised unknown cause of death. The author did not conclude that any of the unknown cause of death cases were related to epilepsy. Petersson et al. 41 studied alcohol as a contributor to mortality and found 61 of 199 deaths to be alcohol-related, none of these deaths were attributed to seizures. Clark 4 reviewed the cause of sudden death in 500 chronic alcoholics. He reported a group of obscure deaths, i.e. deaths where necropsy revealed no distinct cause of death, a certain number (number of cases not stated) of these died apparently of inhalation of vomit, and a few (number not stated) of these deaths were witnessed and epileptic-type seizures described. He concluded that it is possible that most or all of these deaths result from alcohol withdrawal seizures. Some of these cases might be alcoholrelated seizures, but we lack information of possible known epilepsy and epilepsy type. Opeskin et al. 42 presented the most interesting results in this respect. They reported 50 SUDEPs in their study. A necropsy was performed in all cases and by brain examination compared to clinical information a probable cause of epilepsy was determined. In three cases alcohol was thought to be the aetiology of epilepsy. In 23 of the SUDEPs, the circumstances in which the persons were found showed evidence of terminal seizures. Two deaths were observed, one had a GTCS and one was found gasping for air, but without a visible seizure. In another five cases, a seizure was observed within a few hours before death. It is possible that at least one of the three deaths could be in the group with a likely terminal seizure, but no information in the article can verify this. In a study of 10 years ( ) of necropsy reports from this Institute of Forensic Medicine, a total of 2041 cases, 17 cases were identified where the deceased was a known alcoholic and where seizures might have played a role in the death. Causes of death included: head trauma, cerebral lesions, subdural haematoma, cardiac disease, pneumonia, known symptomatic or post-traumatic epilepsy, drowning and drug or alcohol intoxication. None could be attributed to alcohol-induced seizures. Discussion No generally accepted classification of seizures related to alcohol abuse is found in the literature. Most studies offer no definitions. Some authors relate to all cases where alcoholics are known to have a history of seizures as alcoholic epilepsy, some subdivide these into several groups with different stages, 22 others suggest that alcoholics with seizures suffer from some progressing disease other than latent epilepsy due to a lack of abnormalities in EEG outside withdrawal and further differentiate between alcohol withdrawal seizures and alcoholrelated seizures. 43,44 A single study even finds that there might not exist any relation between withdrawal and seizures. 41 It has only been possible to find three documented cases of death where it is acceptable to suggest alcohol abuse as the aetiology of seizures/epilepsy, and as mentioned above we cannot conclude with complete certainty that these persons died from a seizure. Several articles relate to the question of death in alcoholics with late-onset seizures or alcohol withdrawal seizures. Most of these studies can relate all their deaths to pathological findings at necropsy, such as cardiac disease, pneumonia, cerebral tumours, recent or previous head trauma with haematomas or loss of brain substance, intoxication,

4 382 S. Christoffersen etc., 45 or they fail to present their results in such a manner that possible deaths due to alcohol-induced seizures can be identified. Alcohol abuse and withdrawal seizures are associated with GTCS, 18,19,26 28 and alcoholics may progress into SE from their withdrawal seizures. 26,29,30 In epileptics, SE from GTCS is correlated with higher mortality 28 compared to other types. This makes it likely that alcoholics may die from alcohol-induced SE. Then, why do we not see more obvious cases? The literature offers several possible explanations. One study states that alcohol withdrawal seizures are self-limiting in most cases and only a few cases progress into SE. 20 Other studies show higher percentages progressing into SE, but also show that the mortality of SE related to alcohol (or drug) withdrawal is lower than that normally associated with epilepsy. 46,47 Many of the studies regarding alcoholics suffering from seizure disorders include no deaths at all ,33,43,48 51 Most of these are performed in hospitals where acute treatment is at hand, such as anticonvulsive drug therapy, respirator treatment, surgery, etc. This could of course explain why we see few or no deaths in these. In the studies reporting many deaths, the seizures in alcoholics have several aetiologies ranging from metabolic disorders to sequelae from old or recent head trauma. Other possible explanations could be that the hypothesis that alcoholics die from their alcoholinduced seizures is so generally accepted that noone seeks to investigate the correlation, that some of the studies actually include such cases, but fail to present them in a way that they can be identified because their own investigations seek to uncover other relations or maybe because alcoholics rarely or never die from these seizures. Two studies, 52,4 comprising 195 and 500 cases, respectively, with reference to deaths in alcoholics included several cases where no cause of death had been established, and they concluded that several or even many of these deaths were probably due to seizures with alcohol as aetiology. In my opinion, this was not properly documented and must be questioned as almost all other studies, as clarified above, do not find any or at best very few cases where death in this manner could be suspected. Conclusion It has not been possible to find any well-documented deaths due to alcohol-induced seizures. This does of course not necessarily mean that this type of death does not exist at all. But it does suggest that the significance may actually be overestimated on an everyday basis. According to Lowenstein s review from 2006 the most important factor determining the outcome of SE is aetiology 53 and overestimating the significance of an unverified cause of seizure may have fatal consequences for some patients. It is my belief that the matter should be investigated further and that the old truth should only be accepted once it is properly documented. Some of the studies carried out might include cases that fulfil our criteria but fail to present them. If further studies seek to present such cases, they must classify known epileptics into subgroups based on aetiology, and only cases where a necropsy has been performed should be included. 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