Patients sometimes present to the emergency department with seizures related to excessive alcohol use or illicit drug use. These seizures are usually acute symptomatic seizures resulting from substance withdrawal, direct toxic effects of the abused substance on the brain, or from indirect mechanisms, such as head trauma resulting from alcohol or substance abuse. This chapter reviews the mechanisms, clinical manifestations, and principles of management of alcohol-related seizures (ARS) and seizures related to drug abuse.
Alcohol Abuse and Dependence
Recurrent alcohol use resulting in failure to fulfill major role obligations at work, school, or home.
Recurrent alcohol use in situations in which it is physically hazardous.
Recurrent alcohol-related legal problems.
Continued alcohol use despite persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the alcohol.
Alcohol is often taken in larger amounts or over a longer period than was intended.
There is a persistent desire, or there are unsuccessful efforts to cut down or control alcohol use.
A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects.
Important social, occupational, or recreational activities are given up or reduced because of alcohol use.
Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol.
Alcohol-withdrawal seizures/alcohol toxicity seizures.
Seizures associated with traumatic brain injury (TBI) and other intracranial structural lesions.
Metabolic and electrolyte disturbance.
Exacerbation of seizures in a patient with chronic epilepsy.
Withdrawal resulting from the use of concomitant drugs of dependence.
Pathophysiology of Alcohol-Withdrawal Seizures
Studies have shown that chronic alcohol intake inhibits calcium influx through the N-methyl-d-aspartate (NMDA) receptors. This leads to upregulation of NMDA receptors, particularly in the hippocampus and other brain regions with increase in the number and sensitivity of NMDA binding sites. Alcohol also facilitates the action of GABA on chloride channels leading to downregulation of GABA-mediated inhibition. Abrupt cessation of alcohol intake leads to unmasking of the NMDA-mediated excitotoxicity and a reduction in GABA-mediated inhibition leading to neuronal hyperexcitability and withdrawal seizures.
Most ARS are caused by alcohol withdrawal. Alcohol withdrawal is often precipitated by an intercurrent illness, hospital admission, or failure to access alcohol due to other social constraints. Alcohol-dependent patients unable to access alcohol develop an agitated state characterized by irritability, disorientation, hallucinations, tremulousness, tachycardia, hypertension, fever, and myoclonic jerks. If untreated, the patient may progress to delirium tremens. Ninety percent of alcohol-withdrawal seizures occur 6–48 h after cessation of drinking, while 50% occur 13–24 h after cessation of drinking (Ng and Hauser 1988). The seizures are usually generalized tonic-clonic seizures, often multiple, and occurring within no more than 6 h from the onset of the first seizure (Charnes et al. 1989; Freedland and McMicken 1993) They usually develop after many years of heavy drinking (sometimes referred to as “kindling”). Any pattern of seizures deviating from the above description including focal seizures and status epilepticus should raise the possibility of an alternative cause, such as traumatic or hypertensive intracranial hemorrhage and warrants full evaluation including brain imaging (Rathlev et al. 2006). Ictal EEG during alcohol-withdrawal seizures shows findings typical for tonic-clonic seizures. Approximately 50% of patients show a photoconvulsive response for 12–130 h after cessation of drinking prior to treatment with benzodiazepines.
Benzodiazepines are the mainstay of treatment of alcohol withdrawal and ARS (Mckeon et al. 2008). They substitute the GABA-enhancing effects of alcohol, thereby ameliorating the symptoms of alcohol withdrawal. The abused drug should be substituted by a long-acting agent, which should also be available parenterally for ease of administration in an agitated patient. The treatment drug should have low potential for abuse (O’Connor et al. 1994). Lorazepam has an intermediate half-life and does not produce active metabolites (Shaw 1995). It is metabolized by hepatic glucuronidation, which is largely preserved in the cirrhotic liver (Bird and Makela 1994) and has been shown to be as effective as diazepam or chlordiazepoxide (Solomon et al. 1983; Miller and McCurdy 1984; Ritson and Chick 1986). Patients presenting with seizures in the context of acute or chronic alcohol abuse may benefit from the use of lorazepam (D’Onofrio et al. 1999).
Correct fluid and electrolyte disturbances.
Administer 100–200 mg of thiamine intravenously before giving glucose or any carbohydrate-based fluids to prevent depletion of thiamine stores and precipitation of Wernicke’s encephalopathy.
Administer lorazepam 2–4 mg IV or IM to stop the alcohol-withdrawal seizures. This may be followed by lorazepam 2 mg every 2–4 hours as needed, IV, IM or orally to control recurrent withdrawal seizures or other alcohol-withdrawal symptoms.
Screen for sepsis, as a possible cause for failure to access alcohol.
Seizures Associated with Traumatic Brain Injury and Other Intracranial Structural Lesions
Exacerbation of Seizures in Patients with Chronic Epilepsy
Alcohol abuse is often associated with poor adherence to intake of medication and late nights, both of which can lead to the provocation of seizures in epilepsy, especially in adolescents and young adults with primary generalized epilepsy (e.g., juvenile myoclonic epilepsy) (Simon 1988; Renganathan and Delanty 2003). The high-risk period for the occurrence of seizures is during alcohol withdrawal. Prolonged excessive alcohol consumption and some antiepileptic drugs (AEDs) also lead to induction of hepatic enzyme systems, which may increase the metabolism of ethanol and AEDs such as carbamazepine, phenobarbitone, and phenytoin, increasing their clearance rates and decreasing AED levels. This can lead to the reemergence of seizures in previously well-controlled epilepsy patients (Kater et al. 1969).
Metabolic and Electrolyte Disturbance
Alcohol dependence may be associated with metabolic abnormalities and electrolyte disturbance including hypoglycemia, hyponatremia, and hypomagnesemia. The role of such abnormalities in the genesis of seizures in the context of alcohol excess is not clear. It is however important to detect and correct these abnormalities in a patient presenting with ARS. Thiamine should be administered along with intravenous glucose in chronic alcoholic patients to prevent Wernicke–Korsakoff syndrome.
Seizures Associated with Drug Abuse
There are three broad categories of drugs that are commonly abused. (1) benzodiazepines, (2) Opioids, and (3) psychostimulants. Most abused drugs will fall under one of these categories. The main mechanisms leading to seizures in drug abusers are either direct toxicity or withdrawal. Seizures may sometimes result from TBI, stroke, or metabolic derangements complicating drug abuse.
Benzodiazepines are widely prescribed for anxiety disorders, insomnia, and muscle spasms. They enhance the affinity of the recognition site for GABA at its receptor. Both the therapeutic and side effects of benzodiazepines result from the interaction between the benzodiazepine–GABA ionophore complex. Approximately 80% of benzodiazepine abuse is part of polydrug abuse, usually with opioids (Gold et al. 1995). Seizures occur as part of the benzodiazepine withdrawal syndrome usually within 24 h of stopping short-acting agents and within several days of stopping longer-acting agents. The management of benzodiazepine withdrawal seizures is similar to that of alcohol withdrawal.
Naloxone is an opiate antagonist, which is used to reverse the effects of opiate toxicity including seizures. The dose is 0.4 mg by rapid intravenous injection, repeated every 2–3 min until the desired clinical effect is achieved or a total of 10 mg has been administered.
Seizures in the context of stimulant toxicity are terminated by the use of intravenous lorazepam 0.1 mg/kg (maximum of 4 mg). This may be repeated once if the seizure does not stop. Alternatively, diazepam may be used. Prolonged seizures should be managed as status epilepticus in the usual fashion, with intravenous phenytoin. Other measures include control of hyperpyrexia, treatment of hypertension, treatment of cardiac arrhythmias, and treatment of agitation. The unabsorbed drug is removed by gastric lavage.