views & reviews Movement disorders in alcoholism: A review Jack Neiman, MD, PhD;Anthony E. Lang, MD, FRCP(C); Luis Fornazzari, MD, FRCP(C); and Peter L. Carlen, MD, FRCP(C)
Article abstract-A wide variety of movement disorders are associated with alcohol abuse. Some idiopathic movement disorders are markedly improved by small amounts of alcohol and this response occasionally may lead to alcoholism. Alcohol abuse alone or combined with hepatic encephalopathycan cause various types of tremor, asterixis. and cerebellar dysfunction. Alcohol withdrawal is occasionally complicated by transient basal ganglia dysfunction manifested by parkinsonismor chorea. These syndromes are distinct from the movement disorders complicating acquired hepatolenticulardegeneration occurring in some chronic alcoholics. This review discuses the clinical and pathophysiologic aspects of the movement disorder syndromes that complicate alcohol abuse.
NEUROLOGY 1990;40:741-746 Tremor occurs in patients who abuse alcohol (“alcoholic tremor”) particularly during periods of alcohol withdrawal. Alcoholism is also associated with several other movement disorders (table 1). These acute and self-limitedmovement disorderswill be the emphasis of this review. Liver disease is prevalent in chronic alcoholics and liver failure can impair motor control. Furthermore, cerebellar signs are common in alcoholics. Therefore, we also briefly discuss movement disturbances associated with alcoholic liver failure and cerebellar disease. Alcoholic tremor. Alcoholic tremor is most often seen during periods of alcohol withdrawal. It is unclear, however, whether there is a continuum between this acute withdrawal tremor and a form of chronic tremor which is usually less pronounced. The understanding of alcoholic tremor is further complicated by cases of classic essential tremor in the alcoholic population. Alcoholic tremor is of the postural variety. Visually, the tremor often appears irregular due to its variable amplitude.This tremor is most common in the immediate withdrawal period. It mainly d e c t s the hands, but can cause titubation. It is severe only in a minority of alcoholics.1In these severe cases, particularly in those associated with delirium tremens, it may involve all limbs, face, tongue, and even pharyngeal muscles, thereby disturbing phonation.2 Delirium tremens is usually delayed a few days after cessation of drinking following a bout of severe early withdrawal symptoms. Alcoholic tremor disappears during complete relaxation and sleep, and is exacerbated by nervousness.
Movements, particularly the end points of an action, may occasionally increase the amplitude and aggravate the irregularity of tremor so that the patient may complain of considerableclumsiness, even in the absence of true limb ataxia. Alcoholic tremor is characterized by large ampliIt t ~ d ewith ~-~ frequencies varying from 6 to 11Hz.~.‘.~ often persists weeks after discontinuation of alcohol consumption, albeit with decreased amplitude.’ How long alcoholic tremor persists with continued abstinence is not known. Many alcoholics resume drinking after detoxification, rendering follow-up studies difficult. According to 1 study,’ some alcoholics who were alcohol-freefor more than 1year still had a tremor with characteristics similar to those abstinent for shorter periods. Two types of postural tremor have been differentiated in alcoholics.6 The 1st has a frequency exceeding 8 Hz and an alternating EMG pattern in antagonistic muscles. The other is associated with a frequency of less than 8 Hz and with synchronous discrete bursts of EMG activity simultaneously in antagonistic muscles. Both of these EMG patterns can be seen in patients with essential tremor.’ The transient ameliorating effects of alcohol intake on essential tremofl as well as certain other movement disorder^^-^^ are well recognized. In fact, a higher than expected rate of alcoholism in patients with eesential tremor has been reported.13-15 However, large studies from Sweden, Finland, and the United States have shown that alcohol consumption in patients seeking treatment for essential tremor is not different from that in the general population.16-18
From the Neurology Program (Drs. Neiman and Carlen). Addiction Research Foundation, University of Toronto. and Department of Medicine (Neurology) (Dm. Lang and Carlen). Plsyfair Neuroscience Unit, Toronto Western Hospital. Univeraity of Toronto. ON, Canada; the Department of Clinical Alcohol and Drug Addiction Reaearch (Dr. Neiman). Karolinska Institutet. Stockholm. Sweden;and the Clarke Institute of Psychiatry (Dr. Fomaszari). Toronto. ON, Canada. J. Neiman was. in part, supported by s travel grant from the Swedish Society of Medicine. Received August 23.1989. Accepted for publication in final farm October 27.1989. Address correspondence and reprint requeata to Dr. Peter L. Carlen. Neurology Program. Addiction Reaecuch Foundation, 33 Ruseell Street, Toronto. ON, M5S 2S1 Canada. May 1990 NEUROLOGY 40 741
Table 1. Movement disorders associated with alcoholism*t 1. Acute/transient movement disorders in alcoholism: Postural tremor3 Parkinsonism3 Chorea/orolingual dyskinesias3 Akathisia3 2. Variable movement disorders associated with decompensated (alcoholic) liver disease: "Metabolic tremor" Asterixis Myoclonous';!'
3. Movement disorders associated with alcoholic cerebellar degeneration: Cerebellar ataxia 3-Hz leg tremor Parkinsonian tremor 4. Movement disorders (usually persistent) with portosystemic shunts (acquired hepatocerebral degeneration'": Tremor Chorea Dystonia Parkinsonism Myoclonus Cerebellar ataxia
5. Movement disorders responsive to alcohol occasionally resulting in alcoholism: Essential tremor Essential myoclonus Autosomal dominant myoclonic dystonia (Spasmodic torticollis", postanoxic action myoclonus")§
* Consider the possibility that an underlying neurologic disease assciciated with a movement disorder may be the cause of aberrant behavior resulting in alcoholism (eg, Huntington's disease). t Consider the possibility of additional other substance abuse. $ Occurring during alcohol withdrawal. Occurring during alcohol abuse. S Response to alcohol usually mild, alcoholism rarely if ever results.
Pathophysiologic mechanisms underlying alcoholic tremor are not well understood. Several investigators believe it to be primarily an enhanced physiologic t r e m ~ r . ~ Alcoholic .~.'~ tremor probably results from the interaction of a number of factors. It is generally believed that the stimulation of peripheral beta-adrenerpic receptors, caused by the elevated levels of circulating catecholamines during alcohol withdrawal,2O increases the speed of muscle contraction, interferes with neuromuscular transmission or muscle spindle activity, and thereby augments tremor intensity in these patients. The treatment of choice for alcoholic tremor is abstinence from alcohol. In most cases, no pharmacologic intervention is necessary. In persistent and severe cases, beta-receptor blocking agents such as proprano101, started at a low dose (eg, 20 mg twice a day) and gradually increased to 80 to 120mg per day may produce improvement.l.2l We are unaware of formal studies using other beta blockers, primidone, or phenobarbital. Benzodiazepines, used in the treatment of severe alcohol withdrawal,22may also decrease withdrawal symptoms, including tremor, but they are unlikely to be of much use in the treatment of chronic tremor. In alcoholics, other abused substances that provoke 742 NEUROLOGY 40 May 1990
postural tremor should also be considered. Among these are amphetamines and other stimulants.23Nicotine, a powerful alkaloid with both central and peripheral effects, may also enhance postural tremor.24Similar efHowever, the fects have been attributed to ability of nicotine and caffeine to induce tremor has been c ha lle n ge d recent 1y .26.27 Withdraw a1 from opioids,28barbiturates,29and benzodiazepines30is also associated with increased postural tremor. In addition, postural tremor is a feature of the liver failure associated with alcoholism (see below).
Asterixis. Chronic abuse of alcohol is associated with the development of inflammatory and fibrotic liver disease which, if severe enough, can cause an encephalopathy.3' The cardinal features shared by patients with hepatic encephalopathy include a reduced state of awareness and an abnormal EEG,characterized by progressive slowing and the appearance of diffuse delta activity?* which is common in other types of encephalopathy. Triphasic waves have been described as characteristic of hepatic encephalopathy, but this is not universally accepted. Asterixis, possibly the best recognized movement disturbance in these patients, is a disorder of motor control, characterized by brief irregular lapses of posture ("negative myoclonus"). It is best demonstrated as coarse flexion-extension movements of the extended wrists in outstretched hands, but can affect any skeletal muscle of the body. These lapses are associated with involuntary 50- to 200-msec periods of absent electrical activity in muscles that are usually tonically active.33 Asterixis tends to occur in clusters of 2 or 3, followed by a briefly maintained steady posture, whereafter the cycle is repeated, giving the impression of irregular flapping. The more common tremulousness of hepatic encephalopathy ("metabolic tremor") may be a less pronounced manifestation of the same d i s ~ r d e r . ~Here, ~J~ in contrast to asterixis, the pauses in voluntary EMG activity are briefer, less profound, and do not occur simultaneously in all muscles of the limb. The pathophysiologic mechanisms responsible for these disturbances of muscle activity are not known. Asterixis is considered an episodic dysfunction within neural circuits that are normally concerned with maintenance of sustained muscle contraction. These circuits may be vulnerable to generalized neurometabolic changes associated with various disorders including cardiac, respiratory, or renal failure, chronic hemodialysis, and polycythemia." In addition, asterixis can be provoked by various anticonvulsant drugs, toxic doses of salicylates and levodopa, and local lesions in the CNS, particularly in the thalamus, parietal lobe, medial frontal cortex, internal capsule, or rostral midbrain.34 In spite of its relatively nonspecific nature, asterixis is a distinct sign of encephalopathy and, in the setting of alcoholic liver disease, is usually associated with severe hepatic dysfunction. The treatment of hepatic encephalopathy rests on 2 principles: removing precipitants including sedativehypnotic drugs and gastrointestinal bleeding, and de-
creasing the production of ammonia or other possible neuronally active or toxic substances in the bowel. There is no specific treatment for asterixis. The frequency of asterixis diminishes when the hepatic encephalopathy subsides and the mental status of the patient improves.3s
It is possible that other time consumption of factors, such as superimposed supratentorial atrophyq" or difise brain damage due to previous head trauma,46 are needed to manifest cerebellar symptoms, including slow leg tremor. Malnutrition, especially thiamine deficiency, may also be a significant etiologic factor for cerebellar degeneration in chronic alcoholics.38
Three-Hz leg tremor and alcoholic cerebellar signs. Well-known manifestations of the CNS neuBasal ganglia disorders. Transient parkinsonism. As in the nonalcoholic general population, parkinsonrotoxicity of alcohol in chronic alcoholics are the broadism is usually due to idiopathic Parkinson's disease or based gait, dyssynergia, and dysmetria in the lower extremities, consistent with cerebellar damage.36*37 Octo the use of neuroleptic drugs.5oMore rarely, alcohol abuse or withdrawal results in a short-lived parkinsocasionally, tremor resembling a parkinsonian "resting" tremor occurs in the upper limbs, especially when the nian syndrome. To date, there are 12 reported cases of hands are placed in certain sustained positions"8 (and transient parkinsonism, associated with alcohol (table 2). personal observations). A slow rhythmic tremor of the legs, produced by synchronous extension-flexion of hipTransient parkinsonism affects chronic alcoholics of girdle muscles, also occurs in alcoholics.3gThis peculiar both sexes who are over 50 years of age and have little or slow tremor has a frequency of about 3 Hz.It is best no evidence of significant liver dysfunction. This condemonstrated when the patient stands with feet to- dition develops a few days after these patients have had gether and knees half-bent, which produces a slow their last drink or, in some cases, while they are intoxi"bobbing" of the body, or when the patient lies on his cated. They have bradykinesia, stooped posture, shufback with legs elevated and with knee and hip joints fling gait, and lack of associated movements. Some have flexed 90" which causes a typical kicking m o ~ e m e n t . ~ ~an . ~expressionless ~ face, a prominent glabellar reflex, and This rare disorder may affect gait and, in concert with limitation of upward gaze. The majority have a coarse the more common cerebellar ataxia, cause considerable resting tremor with a frequency of 4 to 7 Hz, most often disability in some alcoholics. If the patient abstains localized in both hands and less frequently in the legs, as from alcohol, the intensity of the leg tremor may dewell as cogwheel rigidity of the limbs. Often these pacrease but it usually persists long after cessation of tients also show signs characteristic of alcoholic withdrinking.42There is no specific treatment for this disordrawal and alcoholism including postural tremor, der. ataxia, and confusion. Three-Hz tremor is associated with alcoholic cereMost of the patients reported mild repeated parkinbellar degenerati~n,~~ which affects the anterior supesonian episodes with transient stiffness and occasionrior aspect of the vermis and cerebellar hemispheres. ally resting tremor during previous alcohol withdrawal Degeneration involves all neurocellular elements, but episodes. These alcoholics had neither a family history particularly affects Purkinje ~ e 1 1 s . ~Cerebellar ~ J ~ . ~ ~atroof movement disorder nor a history of neuroleptic use phy can now be diagnosed with the aid of CT or prior to onset of symptoms. CT51 or MRI studiess5 MRI.4s*46 A group of alcoholics with radiologically diagreport equivocal findings. Some patients have moderate nosed cerebellar atrophy was studied with a sway platto severe generalized brain atrophy, most likely due to form. All showed a slow 3-Hz leg tremor.47Moreover, a alcohol abuse.55One patient had bilateral basal ganglia 3-Hz component occurred in 45% of 78 chronic alcocalcification~.~1 holics during measurement of postural sway.48On the Although a short course of biperidenS3 or L-dopa other hand, there was no correlation between cerebellar preparations5' have been tried in an occasional patient atrophy as measured by CT and impaired tandem gait with some success, the condition appears to be selfas measured by the Heath Rail Test.45 limited and all patients improved with abstinence. In According to a recent neuropathologic study, ceresome cases, minimal signs of parkinsonism were presbellar atrophy was verified in over 25% of the 567 alco- ent in the follow-up weeks or months later. However, holics studied.48The fact that only 3 of these alcoholics long-term follow-up has failed to show persistent clinihad been clinically diagnosed antemortem suggests that cal signs (see below). Transient dyskinesias. In 1970, Mullin et alM 1st either clinical testing of cerebellar function is frequently inadequate or cerebellar atrophy alone in alco- reported transient dyskinetic movements in chronic holics is insufficient to cause ataxia. Alternatively, the alcoholics. This condition affects patients younger than cerebellum may have a high reserve capacity so that a those suffering from parkinsonism. Women alcoholics large number of cells must be lost before symptoms seem to be affected more often than men. Dyskinesias usually develop 10to 14 days after cessation of drinking, occur. The cause of alcoholic cerebellar disease, or the neubut may also occur during heavy alcohol abuse.57 romuscular mechanisms underlying the slow leg tremor Neurologic symptoms in these patients include in alcoholics are not known. According to E ~ t r i n , " ~ prominent lingual-oral dyskinesias with twisting and there are no differences in laboratory or physiologic pursing of the mouth, protrusion of the tongue, and markers of alcoholism between alcoholics with and facial grimacing. In some cases, neck and arm muscles without cerebellar damage. Alcoholics with cerebellar are involved. Both sinuous writhing athetotic movedisease, however, may have a higher annual and lifements and more sudden jerky choreic movements can May 1990 NEUROLOGY 40 743
Table 2. Reported cases of alcohol-associated parkinsonism
Reference
Onset of symptoms Chronic Alcohol withdrawal intoxication
Age
Sex
53 56 62
M M F
64 66
M F
70
M
+
Lang et al (1982)52
54
M
+
Shen (1984)53
73 53
50
M M M
55
M
Carlen et al (1981)51
Neiman et al ( 198a5'
+ + +
+
+ + +
occur. The legs are rarely affected. Most patients are not aware of these involuntary movements and some may show bizzare behavior with paranoid ideation, delusions, and hallucinations. Some alcoholics with the parkinsonian syndrome also develop dyskinesias later during alcohol w i t h d r a ~ a l . ~ ' . ~ ~ CT usually shows generalized cerebral atrophy?' but this is a common nonspecific finding in alcoholics. In 1 of Mullin's cases, autopsy showed changes compatible with subacute Wernicke's encephalopathy together with a slight generalized fibrillary gliosis.= The significance of these histologic findings is not clear since tissue changes typical of Wernicke's encephalopathy are frequently seen in alcoholics without movement disordem58 Chronic or persistent choreiform movements also occurred in patients with acquired hepatolenticular or hepatocerebral degeneration (table 1)from severe alcoholic and nonalcoholic liver disease with portosystemic s h ~ n t s . In ~ ~alcoholics .~ with transient dyskinesias, however, there are no severe alterations of liver function tests nor signs of portosystemic encephalopathy. Furthermore, they do not have a family history of movement disorders. Acute alcohol intoxication in younger patients (ages 20 to 30) on chronic neuroleptic treatment may cause short-lived akathisia and dystonia.'jl No specific treatment except for abstinence from alcohol is recommended for these patients, since dyskinesias improve within a few weeks. Chlorpromazine reduced the dyskinesia in 1case.= We suspect that both parkinsonism and dyskinesias may be more common complications of alcoholism than the infrequent reports suggest. We have often seen older 744 NEUROLOGY 40 May 1990
+ + +
Recovery
Other comments
Full within 5 days Almost complete, 2 wks Partial, 6 wks
Two prior episodes Two prior episodes Pill-rolling tremor for 1yr Two prior episodes Pill-rolling tremor for 2 yrs Lingual-oral dyskinesias for 6 mos Two yrs history of shuffling gait
Full, 1wk Parkinsonism: full, 6 wks Dyskinesias: partial, 6 wks Partial, 7 wks almost complete Partial, 4 mos
Four to 5 episodes and 2 episodes after discharge
Full, within 2 mos Full, within 7 days Partial, 1 wk
Two prior episodes One prior episode Two prior episodes
Parkinsonism: full, 4 mos Dyskinesias: full, 4 mos
Several previous episodes with rigidity and shuffling gait
alcoholic patients in early withdrawal with subtle signs of parkinsonism along with the more usual postural tremor, confusion, and ataxia. Moreover,some patients may report transient akathisia.= The pathophysiology of these transient extrapyramidal movement disorders is not clear. Although several neuronal systems might be involved, nigrostriatal dopamine (DA) transmission plays an essential role in the pathogenesis of many similar basal ganglia disorders.62Acutely, alcohol decreases striatal DA releasea and striatal DA-induced adenylate cyclase activitp in experimental animals. On the other hand, prolonged use of alcohol or alcohol withdrawal may induce functional DA receptor supersensitivity, both in experimental animals% and humans.% The mechanism underlying alcohol-induced impairment of DA-mediated transmission is not known. Alcohol may cause increased lipid peroxidation in the nigrostriatal ~ystem,5~ particularly in alcoholics with decreased antioxidant rnechani~ms.~~ Alcoholics with transient parkinsonism might have an underlying nigral degeneration and subclinical Parkinson's disease and develop parkinsonian symptoms because of superimposed alcohol-induced disturbance^.^^ However, in a group of alcoholics with a previous documented episode of transient parkinsonism, none had developed manifest Parkinson's disease in a 10-year follow-up study.68 These findings suggest that the acute syndrome neither reflects progressive nigral pathology, nor predicts the future development of Parkinson's disease.68However, the presence of basal ganglia calcification in 1 earlier case51emphasizes the need to consider the presence of underlying predisposing factors.
Conclusions. Heavy alcohol abuse, alcohol withdrawal, chronic alcohol intake, and chronic hepatic dysfunction due to alcohol toxicity all may be associated with various movement disorders (table 1). Alcohol withdrawal tremor is the commonest and best recognized of all of them. The acute or transient extrapyramidal movement disorder syndromes, seen occasionally during alcohol abuse and more often in the withdrawal period mimic, with 1 exception (ie, the absence of an acute dystonic reaction), the complications of neuroleptic drugs. This may relate to the similarities between the effects of alcohol and these agents on cerebral dopaminergic systems. As emphasized, these syndromes may be much more common than is generally appreciated. Better recognition is obviously important, since a correct diagnosis is essential for prognostic reasons, for selection of appropriate therapy when available, and for avoiding unnecessary pharmacologic intervention. Progress in the understanding of the pathophysiology of these alcohol-related movement disorders may provide new insights into other more commonly recognized basal ganglia diseases.
p a t i e n t s w i t h e s s e n t i a l t r e m o r . Acta Neurol S c a n d 1983i68177- 179. 18. Koller WC. Alcoholism in essential tremor. Neurology 1983;33:1074-1076. 19. Marsden CD. The mechanisms of physiological tremor and their
significance for pathological tremors. Prog Clin Neurophysiol 1978;5:1-16. 20. Carlsaon C, Haggendal J. Arterial noradrenaline levels after ethanol withdrawal. Lancet 1967;2:889. 21. Zilm DH, Sellers EM, MacLeod SM, Degani N. Propranolol effect
o n t r e m o r i n a l c o h o l w i t h d r a w a l . A n n I n t e r n Med 1975;83:234-235. 22. Sellers EM, Naranjo C. Harrison M. Devenyi P. Roach C, Sykora
K. Diazepam loading: simplified treatment of alcohol withdrawal. Clin Pharmacol Ther 1983,34:822-826. 23. Martin WR. Sloan JW, Sapira JD, Jasinski DR. Physiologic, subjective and behavioural effects of amphetamine, metamphetamine, ephedrine, pentrazine and methylphenidate in man. Clin Pharmacol Ther 1971;12:245-258. 24. Shiffman S.Gritz ER, Maltese J, Lee MA, Schneider NG, Jarvik ME. Effects of cigarette smoking and oral nicotine on hand tremor. Clin Pharmacol Ther 1983;33800-805. 25. Weiss B, Laties VG. Enhancement of human performance by caffeine and the amphetamines. Pharmacol Rev 1969141-36. 26. Zdonczyk D, Royse V, Koller WC. Nicotine and tremor. Clin Neuropharmacol 1988;11:282-286. 27. Koller W, Cone S,Herbster G. Caffeine and tremor. Neurology 198T37:169-172. 28. Jaffee JH. Drug addiction anddrug abuse. In: Goodman Gilman A,
Acknowledgment The authors are grateful to Mrs. Yvonne Bedford for typing the manuscript.
References 1. Koller W, O’Hara R, DONSW, Bauer J. Tremor in chronic alco-
holism. Neurology 1985;35:1660-1662. 2. Rondot P, Jedynak CP, Ferrey G. Pathological tremors: noslogical correlates. Prog Clin Neurophysiol 1978;5:95-113. 3. Friedlander WJ. Characteristics of postural tremor in normal and in various abnormal states. Neurology 1956;6716-724. 4. Carrie JRG. Finger tremor in alcoholic patients. J Neurol Neurosurg Psychiatry 1965;28529-532. 5. Zilm DH, Sellers EM, Frecker RC, Kunov H. The nature and etiology of normal and alcohol withdrawal tremor. IEEE Trans Biomed Eng 1979;263-10. 6. Lefebbre-D’Amour M, Shahani BT, Young RR. Tremor in alcoholic patients. Prog Clin Neurophysiol 19785:160-164. 7. Shahani BT, Young RR. Physiological and pharmacological aids in thedifferential diagnosisof tremor. J Neurol Neurosurg Psychiatry 1976;39772-783. 8. Growdon JH, Shahani BT, Young RR. The effect of alcohol on essential tremor. Neurology 1975;25:259-262. 9. Mahloudji M, Pikielny RT. Hereditary essential myoclonus. Brain 1967;90:669-674. 10. Quinn NP, Rothwell JC, Thompson PD, M a d e n CD. Hereditary myoclonic dystonia, hereditary torsion dystonia and hereditary essential myoclonus: a n area of confusion. Adv Neurol 1988;50591-401. 11. Biary N, Koller W. Effect of alcohol on dystonia. Neurology 1985;35:239-240. 12. Fahn S. Posthypoxic action myoclonus: review of the literature
and report of two new cases with responses to valproate and estrogen. Adv Neurol 19792649-84. 13. Nasarallah HA, Schroeder D, Petty F. Alcoholism secondary to essential tremor. J Clin Psychiatry 1981;43:163-164. 14. Schroeder D, Nasarallah HA. High alcoholism rate in patients with essential tremor. Am J Psychiatry 1982;139:1471-1473. 15. Ward K, Potaminanos G, Peters TJ. Essential tremor: a risk factor for alcoholism. Br J Addict 19&1;79451-452. 16. Larason T, Sjagren T. Essential tremor. Acta Psychiatr Neurol Scand 1960;36(Suppl 144):l- 176. 17. Rautakorpi I. Marttila RJ, Rinne UK. Alcohol consumption of
Goodman LS, Rall TW, Murad F, eds.Goodman and Gilman’e the pharmacological basis of therapeutics. New York: MacMillan Publishing, 1985:532-581. 29. Wikler A. Diagnosis and treatment of drug dependence of the barbiturate type. Am J Psychiatry 1968;125:758-765. 30. Mackinnon GL, Parker WA. Benzodiazepine withdrawal syndrome: a literature review and evaluation. Am J Drug Alcohol A b m 1982;919-33. 31. Adams RD, Foley JM. The neurological changes in the more common types of severe liver disease. Trans Am Neurol Assoc 194974~217-219. 32. Capocaccia L, Fischer JE, Rossi-Fanelli F. Assessment and eval-
uation of hepatic encephalopathy. In: Hepatic encephalopathy and chronic liver failure. New York Plenum Press, 1984:239-244. 33. Leavitt S, Tyler HR. Studies in asterixis. Arch Neurol 1964;10360-368. 34. Young RR. Shahani BT. Asterixis: one type of negative myoclonus. Adv Neurol 1986,43:137-157. 35. Sanford NL. Saul RE. Assessment of hepatic encephalopathy
with visual evoked potentials compared with conventional methods. Hepatology 1988,81094-1098. 36. Skillicorn SA. Preaenile cerebellar ataxia in chronic alcoholics. Neurology 19585527-534. 37. Victor M. A d a m RA, Mancall EL. A restricted form of cerebellar cortical degeneration occurring in alcoholic patients. Arch Neurol 19591:579-681. 38. A d a m RD, Victor M. “Alcoholic” cerebellar degeneration. In:
Principlesof neurology, 4th ed. New York McGraw-Hill Information Services. 1989837. 39. Silverskiold BP. Romberg’s test in the cerebellar syndrome occurring i n chronic alcoholism. Acta Neurol Scand 196945:292-302. 40. Silverskiold BP. A 3/sec leg tremor in a cerebellar syndrome. Acta Neurol Scand 1977;55385-393. 41. Rosenhamer HJ, Silverskiold BP. Slow tremor and delayed brain-
stem auditory evoked responses in alcoholics. Arch Neurol 1980,37:293-296. 42. Silverskiold BP. Cortical cerebellar degeneration associated with a specific disorder of standing and locomotion. Acta Neurol Scand 1977;55257-272. 43. Torvik A. Torp S. The prevalence of alcoholic cerebellar atrophg
a morphometric and histological study of an autopsy material. J Neurol Sci 1986,7543-51. 44. Phillips SC. Harper CG, Kril J. A quantitative histological study of t h e cerebellar vermis i n alcoholic patients. Brain 1987;110301-314. 45. Carlen PL, Penn RD, Fornazzari L, Bennett J, Wilkinson DA, May 1990 NEUROLOGY 40 746
Wortzman C. Computerized tomographic scan assessment of alcoholic brain damage and its potential reversibility. Alcoholism Clin Exp Res 1986;10:226-232. 46. Hillbom M. Muuronen A. Holm L, Hindmarsh T. The clinical versus radiological diagnosis of alcoholic cerebellar degeneration. J Neurol Sci 1986,73:45-53. 47. Scholz E, Diener HC, Dichgans J , Langohr HD, Schied W, Schupmann A. Incidence of peripheral neuropathy and cerebellar ataxia in chronic alcoholics. J Neurol 1986,233:212-217. 48. Torvik A, Lindboe CF, Rogde S . Brain lesions in alcoholics. J Neurol Sci 1982;56233-248. 49. Estrin WJ. Alcoholic cerebellar degeneration is not a dose-dependent phenomenon. Alcoholism Clin Exp Res 1987;4:372-375. 50. Marsden CD, Jenner P. The pathophysiology of extrapyramidal side-effects of neuroleptic drugs. Physiol Med 1980;1055-72. 51.Carlen PL, Lee MA, Jacob MA, Livishits 0. Parkinsonism provoked by alcoholism. Ann Neurol 1981;9:84-86. 52. Lang AE, Marsden CD, Obeso JA. Parkes JD. Alcohol and Parkinson disease. Ann Neurol 1982;12:254-256. 53. Shen WW. Extrapyramidal symptoms aseociated with alcohol withdrawal. Biol Psychiatry 1984;191037-1043. 54. Neiman J, Borg S,Wahlund L-0. Parkinsonism and dyskinesias during ethanol withdrawal. Br J Addict 1988;83:437-439. 55. Carlen PL, Wilkinson DA, Wortzman C. et al. Cerebral atrophy and functional deficits in alcoholics without clinically apparent liver disease. Neurology 1981;31:377-385. 56. Mullin PJ, Kershaw PW, Bolt JMW. Choreoathetotic movement disorder in alcoholism. Br Med J 1970;4:278-281. 57. Fornazzari L, Carlen PL. Transient choreiform dyskinesias during alcohol withdrawal. Can J Neurol Sci 1982;989-90. 58. Torvik A. Lindboe CF, Rodge S. Brain lesions in alcoholics. J Neurol Sci 1982;56:233-284.
746 NEUROLOGY 40 May 1990
(non-Wilsonian)type 59. Victor M,AdamsRD.ColeM.Theacquired of c h r o n i c h e p a t o c e r e b r a l d e g e n e r a t i o n . M e d i c i n e 1965;44:345-396. 60. Toghill PJ, Johnston AW, Smith JF. Choreoathetosis in protosystemic encephalopathy. J Neurol Neurosurg Psychiatry 1967;30358-363. 61. Lutz EC. Neuroleptic-inducedakathisiaanddystoniatriggered by alcohol. JAMA 1976;2362422-2423. 62. Rinne UK, Koskinen V, Lonnberg P. Neurotransmitter receptors in the Parkinsonian brain. In: Rinne UK, Klinger M. Stamm G, eds. Parkinson’s disease: current progress, problems and management. Amsterdam: Elsevier/North Holland Biomedical Press, 1980:93-107. 63. Darden JH, Hunt WA. Reduction of striatal dopamine release during a n ethanol withdrawal syndrome. J Neurochem 1977;291143-1145. 64. Lai H. Carino MA, Horito A. Effects of ethanol on central dopamine functions. Life Sci 1980,27:299-301. 65. Liljequiet S. Changes in the sensitivity of dopamine receptors in the nucleus accumbens and in the striatum induced by chronic ethanol administration. Acta Pharmacol Toxicol 197843: 19-28. 66.Balldin J, Alling C, Gottfries CC. Lindstedt G, Langstrom G. Changes in dopamine receptor sensitivity in humans after heavy alcohol intake. Psychopharmacology (Berlin) 1985;86:142-146. 67. Tanner AR, Bantock I. Hinks L, Lloyd B, Turner NR. Wright R. Decreased selenium and vitamin E levels in the alcoholic population: possible relationship to hepatic injury through increased lipid peroxidation. Dig Dis Sci 1986;31:1307-1312. 68.Shandling M, Carlen PL, Lang AE. Parkinsonism in alcohol withdrawal: a follow-up study. Movement Disorders 1990;5:36-39. 69. Fahn S , Marsden CD, Van Woert MH. Definition and classification of myoclonus. Adv Neurol 1986.43:l-5.
Movement disorders in alcoholism: A review Jack Neiman, Anthony E. Lang, Luis Fornazzari, et al. Neurology 1990;40;741 DOI 10.1212/WNL.40.5.741 This information is current as of May 1, 1990 Updated Information & Services
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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1990 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
Article abstract-A wide variety of movement disorders are associated with alcohol abuse. Some idiopathic movement disorders are markedly improved by small amounts of alcohol and this response occasionally may lead to alcoholism. Alcohol abuse alone or combined with hepatic encephalopathycan cause various types of tremor, asterixis. and cerebellar dysfunction. Alcohol withdrawal is occasionally complicated by transient basal ganglia dysfunction manifested by parkinsonismor chorea. These syndromes are distinct from the movement disorders complicating acquired hepatolenticulardegeneration occurring in some chronic alcoholics. This review discuses the clinical and pathophysiologic aspects of the movement disorder syndromes that complicate alcohol abuse.
NEUROLOGY 1990;40:741-746 Tremor occurs in patients who abuse alcohol (“alcoholic tremor”) particularly during periods of alcohol withdrawal. Alcoholism is also associated with several other movement disorders (table 1). These acute and self-limitedmovement disorderswill be the emphasis of this review. Liver disease is prevalent in chronic alcoholics and liver failure can impair motor control. Furthermore, cerebellar signs are common in alcoholics. Therefore, we also briefly discuss movement disturbances associated with alcoholic liver failure and cerebellar disease. Alcoholic tremor. Alcoholic tremor is most often seen during periods of alcohol withdrawal. It is unclear, however, whether there is a continuum between this acute withdrawal tremor and a form of chronic tremor which is usually less pronounced. The understanding of alcoholic tremor is further complicated by cases of classic essential tremor in the alcoholic population. Alcoholic tremor is of the postural variety. Visually, the tremor often appears irregular due to its variable amplitude.This tremor is most common in the immediate withdrawal period. It mainly d e c t s the hands, but can cause titubation. It is severe only in a minority of alcoholics.1In these severe cases, particularly in those associated with delirium tremens, it may involve all limbs, face, tongue, and even pharyngeal muscles, thereby disturbing phonation.2 Delirium tremens is usually delayed a few days after cessation of drinking following a bout of severe early withdrawal symptoms. Alcoholic tremor disappears during complete relaxation and sleep, and is exacerbated by nervousness.
Movements, particularly the end points of an action, may occasionally increase the amplitude and aggravate the irregularity of tremor so that the patient may complain of considerableclumsiness, even in the absence of true limb ataxia. Alcoholic tremor is characterized by large ampliIt t ~ d ewith ~-~ frequencies varying from 6 to 11Hz.~.‘.~ often persists weeks after discontinuation of alcohol consumption, albeit with decreased amplitude.’ How long alcoholic tremor persists with continued abstinence is not known. Many alcoholics resume drinking after detoxification, rendering follow-up studies difficult. According to 1 study,’ some alcoholics who were alcohol-freefor more than 1year still had a tremor with characteristics similar to those abstinent for shorter periods. Two types of postural tremor have been differentiated in alcoholics.6 The 1st has a frequency exceeding 8 Hz and an alternating EMG pattern in antagonistic muscles. The other is associated with a frequency of less than 8 Hz and with synchronous discrete bursts of EMG activity simultaneously in antagonistic muscles. Both of these EMG patterns can be seen in patients with essential tremor.’ The transient ameliorating effects of alcohol intake on essential tremofl as well as certain other movement disorder^^-^^ are well recognized. In fact, a higher than expected rate of alcoholism in patients with eesential tremor has been reported.13-15 However, large studies from Sweden, Finland, and the United States have shown that alcohol consumption in patients seeking treatment for essential tremor is not different from that in the general population.16-18
From the Neurology Program (Drs. Neiman and Carlen). Addiction Research Foundation, University of Toronto. and Department of Medicine (Neurology) (Dm. Lang and Carlen). Plsyfair Neuroscience Unit, Toronto Western Hospital. Univeraity of Toronto. ON, Canada; the Department of Clinical Alcohol and Drug Addiction Reaearch (Dr. Neiman). Karolinska Institutet. Stockholm. Sweden;and the Clarke Institute of Psychiatry (Dr. Fomaszari). Toronto. ON, Canada. J. Neiman was. in part, supported by s travel grant from the Swedish Society of Medicine. Received August 23.1989. Accepted for publication in final farm October 27.1989. Address correspondence and reprint requeata to Dr. Peter L. Carlen. Neurology Program. Addiction Reaecuch Foundation, 33 Ruseell Street, Toronto. ON, M5S 2S1 Canada. May 1990 NEUROLOGY 40 741
Table 1. Movement disorders associated with alcoholism*t 1. Acute/transient movement disorders in alcoholism: Postural tremor3 Parkinsonism3 Chorea/orolingual dyskinesias3 Akathisia3 2. Variable movement disorders associated with decompensated (alcoholic) liver disease: "Metabolic tremor" Asterixis Myoclonous';!'
3. Movement disorders associated with alcoholic cerebellar degeneration: Cerebellar ataxia 3-Hz leg tremor Parkinsonian tremor 4. Movement disorders (usually persistent) with portosystemic shunts (acquired hepatocerebral degeneration'": Tremor Chorea Dystonia Parkinsonism Myoclonus Cerebellar ataxia
5. Movement disorders responsive to alcohol occasionally resulting in alcoholism: Essential tremor Essential myoclonus Autosomal dominant myoclonic dystonia (Spasmodic torticollis", postanoxic action myoclonus")§
* Consider the possibility that an underlying neurologic disease assciciated with a movement disorder may be the cause of aberrant behavior resulting in alcoholism (eg, Huntington's disease). t Consider the possibility of additional other substance abuse. $ Occurring during alcohol withdrawal. Occurring during alcohol abuse. S Response to alcohol usually mild, alcoholism rarely if ever results.
Pathophysiologic mechanisms underlying alcoholic tremor are not well understood. Several investigators believe it to be primarily an enhanced physiologic t r e m ~ r . ~ Alcoholic .~.'~ tremor probably results from the interaction of a number of factors. It is generally believed that the stimulation of peripheral beta-adrenerpic receptors, caused by the elevated levels of circulating catecholamines during alcohol withdrawal,2O increases the speed of muscle contraction, interferes with neuromuscular transmission or muscle spindle activity, and thereby augments tremor intensity in these patients. The treatment of choice for alcoholic tremor is abstinence from alcohol. In most cases, no pharmacologic intervention is necessary. In persistent and severe cases, beta-receptor blocking agents such as proprano101, started at a low dose (eg, 20 mg twice a day) and gradually increased to 80 to 120mg per day may produce improvement.l.2l We are unaware of formal studies using other beta blockers, primidone, or phenobarbital. Benzodiazepines, used in the treatment of severe alcohol withdrawal,22may also decrease withdrawal symptoms, including tremor, but they are unlikely to be of much use in the treatment of chronic tremor. In alcoholics, other abused substances that provoke 742 NEUROLOGY 40 May 1990
postural tremor should also be considered. Among these are amphetamines and other stimulants.23Nicotine, a powerful alkaloid with both central and peripheral effects, may also enhance postural tremor.24Similar efHowever, the fects have been attributed to ability of nicotine and caffeine to induce tremor has been c ha lle n ge d recent 1y .26.27 Withdraw a1 from opioids,28barbiturates,29and benzodiazepines30is also associated with increased postural tremor. In addition, postural tremor is a feature of the liver failure associated with alcoholism (see below).
Asterixis. Chronic abuse of alcohol is associated with the development of inflammatory and fibrotic liver disease which, if severe enough, can cause an encephalopathy.3' The cardinal features shared by patients with hepatic encephalopathy include a reduced state of awareness and an abnormal EEG,characterized by progressive slowing and the appearance of diffuse delta activity?* which is common in other types of encephalopathy. Triphasic waves have been described as characteristic of hepatic encephalopathy, but this is not universally accepted. Asterixis, possibly the best recognized movement disturbance in these patients, is a disorder of motor control, characterized by brief irregular lapses of posture ("negative myoclonus"). It is best demonstrated as coarse flexion-extension movements of the extended wrists in outstretched hands, but can affect any skeletal muscle of the body. These lapses are associated with involuntary 50- to 200-msec periods of absent electrical activity in muscles that are usually tonically active.33 Asterixis tends to occur in clusters of 2 or 3, followed by a briefly maintained steady posture, whereafter the cycle is repeated, giving the impression of irregular flapping. The more common tremulousness of hepatic encephalopathy ("metabolic tremor") may be a less pronounced manifestation of the same d i s ~ r d e r . ~Here, ~J~ in contrast to asterixis, the pauses in voluntary EMG activity are briefer, less profound, and do not occur simultaneously in all muscles of the limb. The pathophysiologic mechanisms responsible for these disturbances of muscle activity are not known. Asterixis is considered an episodic dysfunction within neural circuits that are normally concerned with maintenance of sustained muscle contraction. These circuits may be vulnerable to generalized neurometabolic changes associated with various disorders including cardiac, respiratory, or renal failure, chronic hemodialysis, and polycythemia." In addition, asterixis can be provoked by various anticonvulsant drugs, toxic doses of salicylates and levodopa, and local lesions in the CNS, particularly in the thalamus, parietal lobe, medial frontal cortex, internal capsule, or rostral midbrain.34 In spite of its relatively nonspecific nature, asterixis is a distinct sign of encephalopathy and, in the setting of alcoholic liver disease, is usually associated with severe hepatic dysfunction. The treatment of hepatic encephalopathy rests on 2 principles: removing precipitants including sedativehypnotic drugs and gastrointestinal bleeding, and de-
creasing the production of ammonia or other possible neuronally active or toxic substances in the bowel. There is no specific treatment for asterixis. The frequency of asterixis diminishes when the hepatic encephalopathy subsides and the mental status of the patient improves.3s
It is possible that other time consumption of factors, such as superimposed supratentorial atrophyq" or difise brain damage due to previous head trauma,46 are needed to manifest cerebellar symptoms, including slow leg tremor. Malnutrition, especially thiamine deficiency, may also be a significant etiologic factor for cerebellar degeneration in chronic alcoholics.38
Three-Hz leg tremor and alcoholic cerebellar signs. Well-known manifestations of the CNS neuBasal ganglia disorders. Transient parkinsonism. As in the nonalcoholic general population, parkinsonrotoxicity of alcohol in chronic alcoholics are the broadism is usually due to idiopathic Parkinson's disease or based gait, dyssynergia, and dysmetria in the lower extremities, consistent with cerebellar damage.36*37 Octo the use of neuroleptic drugs.5oMore rarely, alcohol abuse or withdrawal results in a short-lived parkinsocasionally, tremor resembling a parkinsonian "resting" tremor occurs in the upper limbs, especially when the nian syndrome. To date, there are 12 reported cases of hands are placed in certain sustained positions"8 (and transient parkinsonism, associated with alcohol (table 2). personal observations). A slow rhythmic tremor of the legs, produced by synchronous extension-flexion of hipTransient parkinsonism affects chronic alcoholics of girdle muscles, also occurs in alcoholics.3gThis peculiar both sexes who are over 50 years of age and have little or slow tremor has a frequency of about 3 Hz.It is best no evidence of significant liver dysfunction. This condemonstrated when the patient stands with feet to- dition develops a few days after these patients have had gether and knees half-bent, which produces a slow their last drink or, in some cases, while they are intoxi"bobbing" of the body, or when the patient lies on his cated. They have bradykinesia, stooped posture, shufback with legs elevated and with knee and hip joints fling gait, and lack of associated movements. Some have flexed 90" which causes a typical kicking m o ~ e m e n t . ~ ~an . ~expressionless ~ face, a prominent glabellar reflex, and This rare disorder may affect gait and, in concert with limitation of upward gaze. The majority have a coarse the more common cerebellar ataxia, cause considerable resting tremor with a frequency of 4 to 7 Hz, most often disability in some alcoholics. If the patient abstains localized in both hands and less frequently in the legs, as from alcohol, the intensity of the leg tremor may dewell as cogwheel rigidity of the limbs. Often these pacrease but it usually persists long after cessation of tients also show signs characteristic of alcoholic withdrinking.42There is no specific treatment for this disordrawal and alcoholism including postural tremor, der. ataxia, and confusion. Three-Hz tremor is associated with alcoholic cereMost of the patients reported mild repeated parkinbellar degenerati~n,~~ which affects the anterior supesonian episodes with transient stiffness and occasionrior aspect of the vermis and cerebellar hemispheres. ally resting tremor during previous alcohol withdrawal Degeneration involves all neurocellular elements, but episodes. These alcoholics had neither a family history particularly affects Purkinje ~ e 1 1 s . ~Cerebellar ~ J ~ . ~ ~atroof movement disorder nor a history of neuroleptic use phy can now be diagnosed with the aid of CT or prior to onset of symptoms. CT51 or MRI studiess5 MRI.4s*46 A group of alcoholics with radiologically diagreport equivocal findings. Some patients have moderate nosed cerebellar atrophy was studied with a sway platto severe generalized brain atrophy, most likely due to form. All showed a slow 3-Hz leg tremor.47Moreover, a alcohol abuse.55One patient had bilateral basal ganglia 3-Hz component occurred in 45% of 78 chronic alcocalcification~.~1 holics during measurement of postural sway.48On the Although a short course of biperidenS3 or L-dopa other hand, there was no correlation between cerebellar preparations5' have been tried in an occasional patient atrophy as measured by CT and impaired tandem gait with some success, the condition appears to be selfas measured by the Heath Rail Test.45 limited and all patients improved with abstinence. In According to a recent neuropathologic study, ceresome cases, minimal signs of parkinsonism were presbellar atrophy was verified in over 25% of the 567 alco- ent in the follow-up weeks or months later. However, holics studied.48The fact that only 3 of these alcoholics long-term follow-up has failed to show persistent clinihad been clinically diagnosed antemortem suggests that cal signs (see below). Transient dyskinesias. In 1970, Mullin et alM 1st either clinical testing of cerebellar function is frequently inadequate or cerebellar atrophy alone in alco- reported transient dyskinetic movements in chronic holics is insufficient to cause ataxia. Alternatively, the alcoholics. This condition affects patients younger than cerebellum may have a high reserve capacity so that a those suffering from parkinsonism. Women alcoholics large number of cells must be lost before symptoms seem to be affected more often than men. Dyskinesias usually develop 10to 14 days after cessation of drinking, occur. The cause of alcoholic cerebellar disease, or the neubut may also occur during heavy alcohol abuse.57 romuscular mechanisms underlying the slow leg tremor Neurologic symptoms in these patients include in alcoholics are not known. According to E ~ t r i n , " ~ prominent lingual-oral dyskinesias with twisting and there are no differences in laboratory or physiologic pursing of the mouth, protrusion of the tongue, and markers of alcoholism between alcoholics with and facial grimacing. In some cases, neck and arm muscles without cerebellar damage. Alcoholics with cerebellar are involved. Both sinuous writhing athetotic movedisease, however, may have a higher annual and lifements and more sudden jerky choreic movements can May 1990 NEUROLOGY 40 743
Table 2. Reported cases of alcohol-associated parkinsonism
Reference
Onset of symptoms Chronic Alcohol withdrawal intoxication
Age
Sex
53 56 62
M M F
64 66
M F
70
M
+
Lang et al (1982)52
54
M
+
Shen (1984)53
73 53
50
M M M
55
M
Carlen et al (1981)51
Neiman et al ( 198a5'
+ + +
+
+ + +
occur. The legs are rarely affected. Most patients are not aware of these involuntary movements and some may show bizzare behavior with paranoid ideation, delusions, and hallucinations. Some alcoholics with the parkinsonian syndrome also develop dyskinesias later during alcohol w i t h d r a ~ a l . ~ ' . ~ ~ CT usually shows generalized cerebral atrophy?' but this is a common nonspecific finding in alcoholics. In 1 of Mullin's cases, autopsy showed changes compatible with subacute Wernicke's encephalopathy together with a slight generalized fibrillary gliosis.= The significance of these histologic findings is not clear since tissue changes typical of Wernicke's encephalopathy are frequently seen in alcoholics without movement disordem58 Chronic or persistent choreiform movements also occurred in patients with acquired hepatolenticular or hepatocerebral degeneration (table 1)from severe alcoholic and nonalcoholic liver disease with portosystemic s h ~ n t s . In ~ ~alcoholics .~ with transient dyskinesias, however, there are no severe alterations of liver function tests nor signs of portosystemic encephalopathy. Furthermore, they do not have a family history of movement disorders. Acute alcohol intoxication in younger patients (ages 20 to 30) on chronic neuroleptic treatment may cause short-lived akathisia and dystonia.'jl No specific treatment except for abstinence from alcohol is recommended for these patients, since dyskinesias improve within a few weeks. Chlorpromazine reduced the dyskinesia in 1case.= We suspect that both parkinsonism and dyskinesias may be more common complications of alcoholism than the infrequent reports suggest. We have often seen older 744 NEUROLOGY 40 May 1990
+ + +
Recovery
Other comments
Full within 5 days Almost complete, 2 wks Partial, 6 wks
Two prior episodes Two prior episodes Pill-rolling tremor for 1yr Two prior episodes Pill-rolling tremor for 2 yrs Lingual-oral dyskinesias for 6 mos Two yrs history of shuffling gait
Full, 1wk Parkinsonism: full, 6 wks Dyskinesias: partial, 6 wks Partial, 7 wks almost complete Partial, 4 mos
Four to 5 episodes and 2 episodes after discharge
Full, within 2 mos Full, within 7 days Partial, 1 wk
Two prior episodes One prior episode Two prior episodes
Parkinsonism: full, 4 mos Dyskinesias: full, 4 mos
Several previous episodes with rigidity and shuffling gait
alcoholic patients in early withdrawal with subtle signs of parkinsonism along with the more usual postural tremor, confusion, and ataxia. Moreover,some patients may report transient akathisia.= The pathophysiology of these transient extrapyramidal movement disorders is not clear. Although several neuronal systems might be involved, nigrostriatal dopamine (DA) transmission plays an essential role in the pathogenesis of many similar basal ganglia disorders.62Acutely, alcohol decreases striatal DA releasea and striatal DA-induced adenylate cyclase activitp in experimental animals. On the other hand, prolonged use of alcohol or alcohol withdrawal may induce functional DA receptor supersensitivity, both in experimental animals% and humans.% The mechanism underlying alcohol-induced impairment of DA-mediated transmission is not known. Alcohol may cause increased lipid peroxidation in the nigrostriatal ~ystem,5~ particularly in alcoholics with decreased antioxidant rnechani~ms.~~ Alcoholics with transient parkinsonism might have an underlying nigral degeneration and subclinical Parkinson's disease and develop parkinsonian symptoms because of superimposed alcohol-induced disturbance^.^^ However, in a group of alcoholics with a previous documented episode of transient parkinsonism, none had developed manifest Parkinson's disease in a 10-year follow-up study.68 These findings suggest that the acute syndrome neither reflects progressive nigral pathology, nor predicts the future development of Parkinson's disease.68However, the presence of basal ganglia calcification in 1 earlier case51emphasizes the need to consider the presence of underlying predisposing factors.
Conclusions. Heavy alcohol abuse, alcohol withdrawal, chronic alcohol intake, and chronic hepatic dysfunction due to alcohol toxicity all may be associated with various movement disorders (table 1). Alcohol withdrawal tremor is the commonest and best recognized of all of them. The acute or transient extrapyramidal movement disorder syndromes, seen occasionally during alcohol abuse and more often in the withdrawal period mimic, with 1 exception (ie, the absence of an acute dystonic reaction), the complications of neuroleptic drugs. This may relate to the similarities between the effects of alcohol and these agents on cerebral dopaminergic systems. As emphasized, these syndromes may be much more common than is generally appreciated. Better recognition is obviously important, since a correct diagnosis is essential for prognostic reasons, for selection of appropriate therapy when available, and for avoiding unnecessary pharmacologic intervention. Progress in the understanding of the pathophysiology of these alcohol-related movement disorders may provide new insights into other more commonly recognized basal ganglia diseases.
p a t i e n t s w i t h e s s e n t i a l t r e m o r . Acta Neurol S c a n d 1983i68177- 179. 18. Koller WC. Alcoholism in essential tremor. Neurology 1983;33:1074-1076. 19. Marsden CD. The mechanisms of physiological tremor and their
significance for pathological tremors. Prog Clin Neurophysiol 1978;5:1-16. 20. Carlsaon C, Haggendal J. Arterial noradrenaline levels after ethanol withdrawal. Lancet 1967;2:889. 21. Zilm DH, Sellers EM, MacLeod SM, Degani N. Propranolol effect
o n t r e m o r i n a l c o h o l w i t h d r a w a l . A n n I n t e r n Med 1975;83:234-235. 22. Sellers EM, Naranjo C. Harrison M. Devenyi P. Roach C, Sykora
K. Diazepam loading: simplified treatment of alcohol withdrawal. Clin Pharmacol Ther 1983,34:822-826. 23. Martin WR. Sloan JW, Sapira JD, Jasinski DR. Physiologic, subjective and behavioural effects of amphetamine, metamphetamine, ephedrine, pentrazine and methylphenidate in man. Clin Pharmacol Ther 1971;12:245-258. 24. Shiffman S.Gritz ER, Maltese J, Lee MA, Schneider NG, Jarvik ME. Effects of cigarette smoking and oral nicotine on hand tremor. Clin Pharmacol Ther 1983;33800-805. 25. Weiss B, Laties VG. Enhancement of human performance by caffeine and the amphetamines. Pharmacol Rev 1969141-36. 26. Zdonczyk D, Royse V, Koller WC. Nicotine and tremor. Clin Neuropharmacol 1988;11:282-286. 27. Koller W, Cone S,Herbster G. Caffeine and tremor. Neurology 198T37:169-172. 28. Jaffee JH. Drug addiction anddrug abuse. In: Goodman Gilman A,
Acknowledgment The authors are grateful to Mrs. Yvonne Bedford for typing the manuscript.
References 1. Koller W, O’Hara R, DONSW, Bauer J. Tremor in chronic alco-
holism. Neurology 1985;35:1660-1662. 2. Rondot P, Jedynak CP, Ferrey G. Pathological tremors: noslogical correlates. Prog Clin Neurophysiol 1978;5:95-113. 3. Friedlander WJ. Characteristics of postural tremor in normal and in various abnormal states. Neurology 1956;6716-724. 4. Carrie JRG. Finger tremor in alcoholic patients. J Neurol Neurosurg Psychiatry 1965;28529-532. 5. Zilm DH, Sellers EM, Frecker RC, Kunov H. The nature and etiology of normal and alcohol withdrawal tremor. IEEE Trans Biomed Eng 1979;263-10. 6. Lefebbre-D’Amour M, Shahani BT, Young RR. Tremor in alcoholic patients. Prog Clin Neurophysiol 19785:160-164. 7. Shahani BT, Young RR. Physiological and pharmacological aids in thedifferential diagnosisof tremor. J Neurol Neurosurg Psychiatry 1976;39772-783. 8. Growdon JH, Shahani BT, Young RR. The effect of alcohol on essential tremor. Neurology 1975;25:259-262. 9. Mahloudji M, Pikielny RT. Hereditary essential myoclonus. Brain 1967;90:669-674. 10. Quinn NP, Rothwell JC, Thompson PD, M a d e n CD. Hereditary myoclonic dystonia, hereditary torsion dystonia and hereditary essential myoclonus: a n area of confusion. Adv Neurol 1988;50591-401. 11. Biary N, Koller W. Effect of alcohol on dystonia. Neurology 1985;35:239-240. 12. Fahn S. Posthypoxic action myoclonus: review of the literature
and report of two new cases with responses to valproate and estrogen. Adv Neurol 19792649-84. 13. Nasarallah HA, Schroeder D, Petty F. Alcoholism secondary to essential tremor. J Clin Psychiatry 1981;43:163-164. 14. Schroeder D, Nasarallah HA. High alcoholism rate in patients with essential tremor. Am J Psychiatry 1982;139:1471-1473. 15. Ward K, Potaminanos G, Peters TJ. Essential tremor: a risk factor for alcoholism. Br J Addict 19&1;79451-452. 16. Larason T, Sjagren T. Essential tremor. Acta Psychiatr Neurol Scand 1960;36(Suppl 144):l- 176. 17. Rautakorpi I. Marttila RJ, Rinne UK. Alcohol consumption of
Goodman LS, Rall TW, Murad F, eds.Goodman and Gilman’e the pharmacological basis of therapeutics. New York: MacMillan Publishing, 1985:532-581. 29. Wikler A. Diagnosis and treatment of drug dependence of the barbiturate type. Am J Psychiatry 1968;125:758-765. 30. Mackinnon GL, Parker WA. Benzodiazepine withdrawal syndrome: a literature review and evaluation. Am J Drug Alcohol A b m 1982;919-33. 31. Adams RD, Foley JM. The neurological changes in the more common types of severe liver disease. Trans Am Neurol Assoc 194974~217-219. 32. Capocaccia L, Fischer JE, Rossi-Fanelli F. Assessment and eval-
uation of hepatic encephalopathy. In: Hepatic encephalopathy and chronic liver failure. New York Plenum Press, 1984:239-244. 33. Leavitt S, Tyler HR. Studies in asterixis. Arch Neurol 1964;10360-368. 34. Young RR. Shahani BT. Asterixis: one type of negative myoclonus. Adv Neurol 1986,43:137-157. 35. Sanford NL. Saul RE. Assessment of hepatic encephalopathy
with visual evoked potentials compared with conventional methods. Hepatology 1988,81094-1098. 36. Skillicorn SA. Preaenile cerebellar ataxia in chronic alcoholics. Neurology 19585527-534. 37. Victor M. A d a m RA, Mancall EL. A restricted form of cerebellar cortical degeneration occurring in alcoholic patients. Arch Neurol 19591:579-681. 38. A d a m RD, Victor M. “Alcoholic” cerebellar degeneration. In:
Principlesof neurology, 4th ed. New York McGraw-Hill Information Services. 1989837. 39. Silverskiold BP. Romberg’s test in the cerebellar syndrome occurring i n chronic alcoholism. Acta Neurol Scand 196945:292-302. 40. Silverskiold BP. A 3/sec leg tremor in a cerebellar syndrome. Acta Neurol Scand 1977;55385-393. 41. Rosenhamer HJ, Silverskiold BP. Slow tremor and delayed brain-
stem auditory evoked responses in alcoholics. Arch Neurol 1980,37:293-296. 42. Silverskiold BP. Cortical cerebellar degeneration associated with a specific disorder of standing and locomotion. Acta Neurol Scand 1977;55257-272. 43. Torvik A. Torp S. The prevalence of alcoholic cerebellar atrophg
a morphometric and histological study of an autopsy material. J Neurol Sci 1986,7543-51. 44. Phillips SC. Harper CG, Kril J. A quantitative histological study of t h e cerebellar vermis i n alcoholic patients. Brain 1987;110301-314. 45. Carlen PL, Penn RD, Fornazzari L, Bennett J, Wilkinson DA, May 1990 NEUROLOGY 40 746
Wortzman C. Computerized tomographic scan assessment of alcoholic brain damage and its potential reversibility. Alcoholism Clin Exp Res 1986;10:226-232. 46. Hillbom M. Muuronen A. Holm L, Hindmarsh T. The clinical versus radiological diagnosis of alcoholic cerebellar degeneration. J Neurol Sci 1986,73:45-53. 47. Scholz E, Diener HC, Dichgans J , Langohr HD, Schied W, Schupmann A. Incidence of peripheral neuropathy and cerebellar ataxia in chronic alcoholics. J Neurol 1986,233:212-217. 48. Torvik A, Lindboe CF, Rogde S . Brain lesions in alcoholics. J Neurol Sci 1982;56233-248. 49. Estrin WJ. Alcoholic cerebellar degeneration is not a dose-dependent phenomenon. Alcoholism Clin Exp Res 1987;4:372-375. 50. Marsden CD, Jenner P. The pathophysiology of extrapyramidal side-effects of neuroleptic drugs. Physiol Med 1980;1055-72. 51.Carlen PL, Lee MA, Jacob MA, Livishits 0. Parkinsonism provoked by alcoholism. Ann Neurol 1981;9:84-86. 52. Lang AE, Marsden CD, Obeso JA. Parkes JD. Alcohol and Parkinson disease. Ann Neurol 1982;12:254-256. 53. Shen WW. Extrapyramidal symptoms aseociated with alcohol withdrawal. Biol Psychiatry 1984;191037-1043. 54. Neiman J, Borg S,Wahlund L-0. Parkinsonism and dyskinesias during ethanol withdrawal. Br J Addict 1988;83:437-439. 55. Carlen PL, Wilkinson DA, Wortzman C. et al. Cerebral atrophy and functional deficits in alcoholics without clinically apparent liver disease. Neurology 1981;31:377-385. 56. Mullin PJ, Kershaw PW, Bolt JMW. Choreoathetotic movement disorder in alcoholism. Br Med J 1970;4:278-281. 57. Fornazzari L, Carlen PL. Transient choreiform dyskinesias during alcohol withdrawal. Can J Neurol Sci 1982;989-90. 58. Torvik A. Lindboe CF, Rodge S. Brain lesions in alcoholics. J Neurol Sci 1982;56:233-284.
746 NEUROLOGY 40 May 1990
(non-Wilsonian)type 59. Victor M,AdamsRD.ColeM.Theacquired of c h r o n i c h e p a t o c e r e b r a l d e g e n e r a t i o n . M e d i c i n e 1965;44:345-396. 60. Toghill PJ, Johnston AW, Smith JF. Choreoathetosis in protosystemic encephalopathy. J Neurol Neurosurg Psychiatry 1967;30358-363. 61. Lutz EC. Neuroleptic-inducedakathisiaanddystoniatriggered by alcohol. JAMA 1976;2362422-2423. 62. Rinne UK, Koskinen V, Lonnberg P. Neurotransmitter receptors in the Parkinsonian brain. In: Rinne UK, Klinger M. Stamm G, eds. Parkinson’s disease: current progress, problems and management. Amsterdam: Elsevier/North Holland Biomedical Press, 1980:93-107. 63. Darden JH, Hunt WA. Reduction of striatal dopamine release during a n ethanol withdrawal syndrome. J Neurochem 1977;291143-1145. 64. Lai H. Carino MA, Horito A. Effects of ethanol on central dopamine functions. Life Sci 1980,27:299-301. 65. Liljequiet S. Changes in the sensitivity of dopamine receptors in the nucleus accumbens and in the striatum induced by chronic ethanol administration. Acta Pharmacol Toxicol 197843: 19-28. 66.Balldin J, Alling C, Gottfries CC. Lindstedt G, Langstrom G. Changes in dopamine receptor sensitivity in humans after heavy alcohol intake. Psychopharmacology (Berlin) 1985;86:142-146. 67. Tanner AR, Bantock I. Hinks L, Lloyd B, Turner NR. Wright R. Decreased selenium and vitamin E levels in the alcoholic population: possible relationship to hepatic injury through increased lipid peroxidation. Dig Dis Sci 1986;31:1307-1312. 68.Shandling M, Carlen PL, Lang AE. Parkinsonism in alcohol withdrawal: a follow-up study. Movement Disorders 1990;5:36-39. 69. Fahn S , Marsden CD, Van Woert MH. Definition and classification of myoclonus. Adv Neurol 1986.43:l-5.
Movement disorders in alcoholism: A review Jack Neiman, Anthony E. Lang, Luis Fornazzari, et al. Neurology 1990;40;741 DOI 10.1212/WNL.40.5.741 This information is current as of May 1, 1990 Updated Information & Services
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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1990 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
