Alcohol-Related Neurologic Disease
Alcohol-Related Neurologic Disease
Alcohol, or ethanol, is a poison with direct toxic effects on nerve and muscle cells. Depending on which nerve and muscle pathways are involved, alcohol can have far-reaching effects on different parts of the brain, peripheral nerves, and muscles, with symptoms of memory loss, incoordination, seizures, weakness, and sensory deficits. These different effects can be grouped into three main categories: (1) intoxication due to the acute effects of ethanol, (2) withdrawal syndrome from suddenly stopping drinking, and (3) disorders related to long-term or chronic alcohol abuse. Alcohol-related neurologic disease includes Wernicke-Korsakoff disease, alcoholic cerebellar degeneration, alcoholic myopathy, alcoholic neuropathy, alcohol withdrawal syndrome with seizures and delirium tremens, and fetal alcohol syndrome.
Acute excess intake of alcohol can cause drunkenness (intoxication) or even death, and chronic or long-term abuse leads to potentially irreversible damage to virtually any level of the nervous system. Any given patient with long-term alcohol abuse may have no neurologic complications, a single alcohol-related disease, or multiple conditions, depending on the genes they have inherited, how well nourished they are, and other environmental factors, such as exposure to other drugs or toxins.
Neurologic complications of alcohol abuse may also result from nutritional deficiency, because alcoholics tend to eat poorly and may become depleted of thiamine or other vitamins important for nervous system function. Persons who are intoxicated are also at higher risk for head injury or for compression injuries of the peripheral nerves. Sudden changes in blood chemistry, especially sodium, related to alcohol abuse may cause central pontine myelinolysis, a condition of the brainstem in which nerves lose their myelin coating. Liver disease complicating alcoholic cirrhosis may cause dementia, delirium, and movement disorder.
Causes and symptoms
When a person drinks alcohol, it is absorbed by blood vessels in the stomach lining and flows rapidly throughout the body and brain, as ethanol freely crosses the blood-brain barrier that ordinarily keeps large molecules from escaping from the blood vessel to the brain tissue. Drunkenness, or intoxication, may occur at blood ethanol concentrations of as low as 50-150 mg per dL in people who don't drink. Sleepiness, stupor, coma, or even death from respiratory depression and low blood pressure occur at progressively higher concentrations.
Although alcohol is broken down by the liver, the toxic effects from a high dose of alcohol are most likely a direct result of alcohol itself rather than of its breakdown products. The fatal dose varies widely because people who drink heavily develop a tolerance to the effects of alcohol with repeated use. In addition, alcohol tolerance results in the need for higher levels of blood alcohol to achieve intoxicating effects, which increases the likelihood that habitual drinkers will be exposed to high and potentially toxic levels of ethanol. This is particularly true when binge drinkers fail to eat, because fasting decreases the rate of alcohol clearance and causes even higher blood alcohol levels.
When a chronic alcoholic suddenly stops drinking, withdrawal of alcohol leads to a syndrome of increased excitability of the central nervous system, called delirium tremens or "DTs." Symptoms begin six to eight hours after abstinence, and are most pronounced 24-72 hours after abstinence. They include body shaking (tremulousness), insomnia, agitation, confusion, hearing voices or seeing images that are not really there (such as crawling bugs), seizures, rapid heart beat, profuse sweating, high blood pressure, and fever. Alcohol-related seizures may also occur without withdrawal, such as during active heavy drinking or after more than a week without alcohol.
Wernicke-Korsakoff syndrome is caused by deficiency of the B-vitamin thiamine, and can also be seen in people who don't drink but have some other cause of thiamine deficiency, such as chronic vomiting that prevents the absorption of this vitamin. A 2004 study demonstrated that alcohol-dependent patients admitted to a detoxification facility had consumed significantly less thiamine than a comparison group of healthy volunteers. Patients with this condition have the sudden onset of Wernicke encephalopathy; the symptoms include marked confusion, delirium, disorientation, inattention, memory loss, and drowsiness. Examination reveals abnormalities of eye movement, including jerking of the eyes (nystagmus ) and double vision. Problems with balance make walking difficult. People may have trouble coordinating their leg movements, but usually not their arms. If thiamine is not given promptly, Wernicke encephalopathy may progress to stupor, coma, and death.
Abstinence— Refraining from the use of alcoholic beverages.
Atrophy— A wasting or decrease in size of a muscle or other tissue.
Cerebellum— The part of the brain involved in coordination of movement, walking, and balance.
Degeneration— Gradual, progressive loss of nerve cells.
Delirium— Sudden confusion with decreased or fluctuating level of consciousness.
Delirium tremens— A complication that may accompany alcohol withdrawal. The symptoms include body shaking (tremulousness), insomnia, agitation, confusion, hearing voices or seeing images that are not really there (hallucinations), seizures, rapid heart beat, profuse sweating, high blood pressure, and fever.
Dementia— Loss of memory and other higher functions, such as thinking or speech, lasting six months or more.
Myoglobinuria— Reddish urine caused by excretion of myoglobin, a breakdown product of muscle.
Myopathy— A disorder that causes weakening of muscles.
Neuropathy— A condition affecting the nerves supplying the arms and legs. Typically, the feet and hands are involved first. If sensory nerves are involved, numbness, tingling, and pain are prominent, and if motor nerves are involved, the patient experiences weakness.
Thiamine— A B vitamin essential for the body to process carbohydrates and fats. Alcoholics may suffer complications (including Wernike-Korsakoff syndrome) from a deficiency of this vitamin.
Wernicke-Korsakoff syndrome— A combination of symptoms, including eye-movement problems, tremors, and confusion, that is caused by a lack of the B vitamin thiamine and may be seen in alcoholics.
If thiamine is given and death averted, Korsakoff's syndrome may develop in some patients, who suffer from memory impairment that leaves them unable to remember events for a period of a few years before the onset of illness (retrograde amnesia ) and unable to learn new information (anterograde amnesia). Most patients have very limited insight into their memory dysfunction and have a tendency to make up explanations for events they have forgotten (confabulation).
Severe alcoholism can cause cerebellar degeneration, a slowly progressive condition affecting portions of the brain called the anterior and superior cerebellar vermis, causing a wide-based gait, leg incoordination, and an inability to walk heel-to-toe in tightrope fashion. The gait disturbance usually develops over several weeks, but may be relatively mild for some time, and then suddenly worsen after binge drinking or an unrelated illness.
Fetal alcohol syndrome occurs in infants born to alcoholic mothers when prenatal exposure to ethanol retards fetal growth and development. Affected infants often have a distinctive appearance with a thin upper lip, flat nose and mid-face, short stature and small head size. Almost half are mentally retarded, and most others are mildly impaired intellectually or have problems with speech, learning, and behavior. Fetal alcohol syndrome is the leading cause of mental retardation and many physicians warn that there is no safe level of alcohol for a pregnant mother to consume.
Alcoholic myopathy, or weakness secondary to breakdown of muscle tissue, is also known as alcoholic rhabdomyolysis or alcoholic myoglobinuria. Males are affected by acute (sudden onset) alcoholic myopathy four times as often as females. Breakdown of muscle tissue (myonecrosis), can come on suddenly during binge drinking or in the first days of alcohol withdrawal. In its mildest form, this breakdown may cause no noticeable symptoms, but may be detected by a temporary elevation in blood levels of an enzyme found predominantly in muscle, the MM fraction of creatine kinase.
The severe form of acute alcoholic myopathy is associated with the sudden onset of muscle pain, swelling, and weakness; a reddish tinge in the urine caused by myoglobin, a breakdown product of muscle excreted in the urine; and a rapid rise in muscle enzymes in the blood. Symptoms usually worsen over hours to a few days, and then improve over the next week to 10 days as the patient is withdrawn from alcohol. Muscle symptoms are usually generalized, but pain and swelling may selectively involve the calves or other muscle groups. The muscle breakdown of acute alcoholic myopathy may be worsened by crush injuries, which may occur when people drink so much that they compress a muscle group with their body weight for a long time without moving, or by withdrawal seizures with generalized muscle activity.
In patients who abuse alcohol over many years, chronic alcoholic myopathy may develop. Males and females are equally affected. Symptoms include painless weakness of the limb muscles closest to the trunk and the girdle muscles, including the thighs, hips, shoulders, and upper arms. This weakness develops gradually, over weeks or months, without symptoms of acute muscle injury. Muscle atrophy, or decreased bulk, may be striking. The nerves of the extremities may also begin to break down, a condition known as alcoholic peripheral neuropathy, which can add to the person's difficulty in moving.
The way in which alcohol destroys muscle tissue is still not well understood. Proposed mechanisms include muscle membrane changes affecting the transport of calcium, potassium, or other minerals; impaired muscle energy metabolism; and impaired protein synthesis. Alcohol is metabolized or broken down primarily by the liver, with a series of chemical reactions in which ethanol is converted to acetate. Acetate is metabolized by skeletal muscle, and alcohol-related changes in liver function may affect skeletal muscle metabolism, decreasing the amount of blood sugar available to muscles during prolonged activity. Because not enough sugar is available to supply needed energy, muscle protein may be broken down as an alternate energy source. However, toxic effects on muscle may be a direct result of alcohol itself rather than of its breakdown products.
Although alcoholic peripheral neuropathy may contribute to muscle weakness and atrophy by injuring the motor nerves controlling muscle movement, alcoholic neuropathy more commonly affects sensory fibers. Injury to these fibers can cause tingling or burning pain in the feet, which may be severe enough to interfere with walking. As the condition worsens, pain decreases but numbness increases.
The diagnosis of alcohol-related neurologic disease depends largely on finding characteristic symptoms and signs in patients who abuse alcohol. Other possible causes should be excluded by the appropriate tests, which may include blood chemistry, thyroid function tests, brain MRI (magnetic resonance imaging ) or CT (computed tomography scan), and/or cerebrospinal fluid analysis.
Acute alcoholic myopathy can be diagnosed by finding myoglobin in the urine and increased creatine kinase and other blood enzymes released from injured muscle. The surgical removal of a small piece of muscle for microscopic analysis (muscle biopsy) shows the scattered breakdown and repair of muscle fibers. Doctors must rule out other acquired causes of muscle breakdown, which include the abuse of drugs such as heroin, cocaine, or amphetamines; trauma with crush injury; the depletion of phosphate or potassium; or an underlying defect in the metabolism of carbohydrates or lipids. In chronic alcoholic myopathy, serum creatine kinase often is normal, and muscle biopsy shows atrophy, or loss of muscle fibers. Electromyography (EMG) may show features characteristic of alcoholic myopathy or neuropathy.
Acute management of alcohol intoxication, delirium tremens, and withdrawal is primarily supportive, to monitor and treat any cardiovascular or respiratory failure that may develop. In delirium tremens, fever and sweating may necessitate treatment of fluid loss and secondary low blood pressure. Agitation may be treated with benzodiazepines such as chlordiazepoxide, beta-adrenergic antagonists such as atenolol, or alpha 2-adrenergic agonists such as clonidine. Because Wernicke's syndrome is rapidly reversible with thiamine, and because death may intervene if thiamine is not given promptly, all patients admitted for acute complications of alcohol, as well as all patients with unexplained encephalopathy, should be given intravenous thiamine.
Withdrawal seizures typically resolve without specific anti-epileptic drug treatment, although status epilepticus (continual seizures occurring without interruption) should be treated vigorously. Acute alcoholic myopathy with myoglobinuria requires monitoring and maintenance of kidney function, and correction of imbalances in blood chemistry including potassium, phosphate, and magnesium levels.
Chronic alcoholic myopathy and other chronic conditions are treated by correcting associated nutritional deficiencies and maintaining a diet adequate in protein and carbohydrate. The key to treating any alcohol-related disease is helping the patient overcome alcohol addiction. Behavioral measures and social supports may be needed in patients who develop broad problems in their thinking abilities (dementia) or remain in a state of confusion and disorientation (delirium). People with walking disturbances may benefit from physical therapy and assistive devices. Doctors may also prescribe drugs to treat the pain associated with peripheral neuropathy.
Complete recovery from Wernicke's syndrome may follow prompt administration of thiamine. However, repeated episodes of encephalopathy or prolonged alcohol abuse may cause persistent dementia or Korsakoff psychosis. Most patients recover fully from acute alcoholic myopathy within days to weeks, but severe cases may be fatal from acute kidney failure and disturbances in heart rhythm secondary to increased potassium levels. Recovery from chronic alcoholic myopathy may occur over weeks to months of abstinence from alcohol and correction of malnutrition. Cerebellar degeneration and alcoholic neuropathy may also improve to some extent with abstinence and balanced diet, depending on the severity and duration of the condition.
Prevention requires abstinence from alcohol. Persons who consume small or moderate amounts of alcohol might theoretically help prevent nutritional complications of alcohol use with dietary supplements including B vitamins. However, proper nutrition cannot protect against the direct toxic effect of alcohol or of its breakdown products. Patients with any alcohol-related symptoms or conditions, pregnant women, and patients with liver or neurologic disease should abstain completely. Persons with family history of alcoholism or alcohol-related conditions may also be at increased risk for neurologic complications of alcohol use.
"Missouri Clinics Will Diagnose and Treat Fetal Alcohol Syndrome." Mental Health Weekly Digeste (June 7, 2004): 33.
Stacey, Philip S. "Preliminary Investigation of Thiamine and Alcohol Intake in Clinical and Healthy Samples." Psychological Reports (June 2004): 845-849.
National Institute on Alcohol Abuse and Alcoholism. 6000 Executive Boulevard, Willco Building, Bethesda, MD 20892-7003. 〈http://silk.nih.gov/silk/niaaa1〉.