Reference Work Entry

Atlas of Epilepsies

pp 165-170

Alcohol and Illicit Drug Abuse Associated with Epileptic Seizures

  • Elijah ChailaAffiliated withDepartment of Neurology, Beaumont Hospital, Epilepsy Programme
  • , Norman DelantyAffiliated withDepartment of Neurology, Beaumont Hospital, Epilepsy Programme


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

The Diagnostic and Statistical Manual-IV (DSM-IV) defines alcohol abuse as a maladaptive pattern of alcohol use leading to clinically significant impairment or distress, as manifested by one or more of the following, occurring within a 12-month period:
  1. 1.

    Recurrent alcohol use resulting in failure to fulfill major role obligations at work, school, or home.

  2. 2.

    Recurrent alcohol use in situations in which it is physically hazardous.

  3. 3.

    Recurrent alcohol-related legal problems.

  4. 4.

    Continued alcohol use despite persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the alcohol.

The symptoms must never have met the criteria for alcohol dependence.
Dependence is a maladaptive pattern of alcohol use leading to clinically significant impairment or distress, as manifested by three or more of the following seven criteria, occurring at any time in the same 12-month period:
  1. 1.


  2. 2.

    Alcohol withdrawal.

  3. 3.

    Alcohol is often taken in larger amounts or over a longer period than was intended.

  4. 4.

    There is a persistent desire, or there are unsuccessful efforts to cut down or control alcohol use.

  5. 5.

    A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects.

  6. 6.

    Important social, occupational, or recreational activities are given up or reduced because of alcohol use.

  7. 7.

    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-Related Seizures

Alcohol-related seizures (ARS) are seizures that occur in the context of chronic alcohol dependence. The relationship between alcohol and seizures is multifaceted (Fig. 22-1 ). Broadly, there are multiple possible causes of ARS including the following:
  1. 1.

    Alcohol-withdrawal seizures/alcohol toxicity seizures.

  2. 2.

    Seizures associated with traumatic brain injury (TBI) and other intracranial structural lesions.

  3. 3.

    Metabolic and electrolyte disturbance.

  4. 4.

    Exacerbation of seizures in a patient with chronic epilepsy.

  5. 5.

    Withdrawal resulting from the use of concomitant drugs of dependence.
Figure 22-1

The complex interplay between alcohol and seizures

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.

Alcohol-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).

The following are proposed treatment guidelines for alcohol-withdrawal seizures:
  1. 1.

    Correct fluid and electrolyte disturbances.

  2. 2.

    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.

  3. 3.

    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.

  4. 4.

    Screen for sepsis, as a possible cause for failure to access alcohol.

Phenytoin has no role in the treatment of alcohol-withdrawal seizures (Rathlev et al. 1994) unless the patient develops status epilepticus. Routine seizure prophylaxis is not recommended for alcohol-withdrawal seizures. For patients whose seizures are not temporally related to alcohol intake, or a lack there of, prophylactic anticonvulsant treatment may be necessary although adherence to treatment may be generally poor.

Seizures Associated with Traumatic Brain Injury and Other Intracranial Structural Lesions

Alcohol consumption is a strong predisposing factor for traumatic brain injury (TBI). Head trauma can lead to cerebral contusion, subdural hematoma, extradural hemorrhage (Fig. 22-2 ), intracerebral hematoma (Fig. 22-3 ), and subarachnoid hemorrhage (Fig. 22-4 ). Following injury to the brain, patients may develop seizures acutely (acute symptomatic seizures) or after a latent period (remote symptomatic seizures, i.e., epilepsy). TBI accounts for 4% of epilepsy (Herman 2002). A significant number of patients (up to 30%) admitted with ARS have been found to have associated structural intracranial abnormalities. Intuitively, one would expect that all the structural abnormalities in the context of ARS would be related to trauma. However, other possible abnormalities include vascular and neoplastic lesions (Earnest and Yarnell 1976; Hillbom 1980). Many heavy drinkers tend to be heavy smokers, increasing the risk for vascular events. Some studies indicate that patients who consume excessive amounts of alcohol have an increased risk for primary subarachnoid hemorrhage (Hillbom and Kaste 1982) and hemorrhagic stroke (Weisber 1988; Gill et al. 1991), which may lead to an increased risk for the development of symptomatic seizures and epilepsy (Yamane and Kiatoh 1981).
Figure 22-2

This 25-year-old man sustained blunt trauma to the head while under the influence of alcohol. CT scan of the brain showed a left extradural hematoma with overlying soft tissue swelling
Figure 22-3

Right frontal lobe contusion. This 55-year-old man slipped and fell down the stairs after consuming several drinks. He presented with a tonic-clonic seizure with head version to the left within a few hours of the injury
Figure 22-4

This patient was found collapsed at the bottom of the stairs. He had consumed a moderate amount of alcohol earlier that day. CT brain shows a right parietal-occipital extradural hematoma with left temporal sub-arachnoid hemorrhage

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.


Opioids are a class of drugs that are commonly used for pain control. Included are drugs such as morphine, heroin (Fig. 22-5 ), pethidine, methadone, and codeine. Seizures and myoclonic jerks may accompany pethidine toxicity due to its pro-convulsant metabolite, nor-pethidine (Kaiko et al. 1983). It is important to note that seizures do not occur during opioid withdrawal (Kosten and O’Connor 2003); therefore, any seizures accompanying opioid withdrawal should suggest either concomitant use of another drug or central nervous system infection, especially in the setting of intravenous drug abuse.
Figure 22-5

Diacetylmorphine (heroin) is a semi-synthetic opioid, which is used as a strong analgesic. Its popular use however is for recreational purposes as it produces euphoria and relaxation. It is addictive and needle sharing has resulted in transmission of HIV and hepatitis B and C. It is a controlled drug. Reproduced from US Drug Enforcement Administration Multimedia library

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.


The two most popular agents in this category of drugs are cocaine (Figs. 22-6 22-8 ) and amphetamines. Amphetamines are a group of drugs that increase the levels of nor-epinephrine, serotonin, and dopamine in the brain. Drugs that contain amphetamine-like compounds include both prescription (e.g., ephedrine) and recreational drugs. Routes of intake include oral, snorting, smoking, and intravenous injection. Cocaine is derived from the leaves of the coca plant in South and Central America. It is mainly used as a recreational drug. Routes of intake include smoking, snorting, and intravenous injection. Psychostimulant drugs cause hyperactivity, restlessness, mydriasis, flushing, euphoria, and feelings of well-being. Toxicity causes fever, hypertension, cardiac arrhythmias, delirium, or coma. With the use of amphetamine-like drugs, seizures are often accompanied by other signs of toxicity (Alldredge et al. 1989), while with cocaine abuse, seizures occur without other signs of toxicity. Cocaine-induced seizures may occur immediately or several hours after use, and are probably attributable to its active metabolites (Myers and Earnest 1984; Harden et al. 1990). Seizures are more likely to occur after smoking alkaloid cocaine. The prevalence of seizures in patients intoxicated with cocaine is up to 10% (Choy-Kwong and Lipton 1989; Pascal-Leone et al. 1990). Cocaine and amphetamines may also cause stroke, either ischemic or hemorrhagic. Cocaine is the most important cause of drug-induced stroke. Amphetamines may also cause a small-vessel vasculitis. It is therefore important to exclude a structural lesion if a patient presents with a focal seizure in the context of psychostimulant drug abuse. Methylene-dioxymethamphetamine (MDMA) or “ecstasy” (Fig. 22-9 ) is a drug that is popular with students for use at parties and other social gatherings. It combines both psychostimulant and hallucinogenic effects and its use can also cause seizures, usually in the setting of other signs of toxicity such as rhabdomyolysis.
Figure 22-6

The coca plant, erythroxylon
Figure 22-7

Cocaine is a psychostimulant, which may be smoked (“crack cocaine”), used intranasally or injected intravenously. The metabolite, benzoylecgonine, can be found in urine 7–10 days after frequent high dose use. Reproduced with permission from US Drug Enforcement Administration Multimedia library
Figure 22-8

3,4-Methylenedioxymethamphetamine (MDMA) also called “ecstasy” is a psychostimulant and has been a popular drug at rave parties. It produces stimulant and hallucinogenic effects. Reproduced with permission from US Drug Enforcement Administration Multimedia library
Figure 22-9

Lysergic acid diethylamide (LSD) is a hallucinogenic, psychedelic drug, which produces auditory and visual perception changes. It produces multicolored visions with illusions of movement of static objects. It can produce psychosis. It has mainly been used for recreational purposes, but it is illegal to possess LSD without a license. Reproduced with permission from US Drug Enforcement Administration Multimedia library

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.

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