Doi:10.1016/j.ncl.2005.11.00

aDepartment of Neurology, Johns Hopkins University School of Medicine, bNeurological Institute, Columbia University College of Physicians and Surgeons, Those who survive cardiac arrest often experience significant neurologic impairment. A rare, but often debilitating, consequence of cardiac arrest isthe development of movement disorders. A wide range of movement dis-orders, with many different causes, is observed after cardiac arrest. Cardiacarrest survivors may develop movement disorders from metabolic distur-bances resulting from hypoxic-ischemic damage to the liver or kidney,from medications administered to treat other complications of cardiac arrest,or from cardioembolic ischemic stroke as a result of impaired myocardium orcardiac valves. This review focuses on movement disorders caused by cere-bral hypoxia after cardiac arrest. Many different movement disorders are de-scribed after hypoxic-ischemic brain injury, including parkinsonism,dystonia, chorea, tics, athetosis, tremor, and myoclonus Of thesemovement disorders, the one reported and investigated most extensively isposthypoxic myoclonus (PHM). Hence, this article describes the clinicalspectrum, pathophysiology, and treatment of PHM before briefly discussingother posthypoxic movement disorders.
Myoclonus refers to sudden, shock-like, involuntary movements that can manifest in various patterns. Myoclonus may be focal, where a few adjacentmuscles are involved; multifocal, where many muscles jerk asynchronously;or generalized, where most of the muscles of the body are involved in * Corresponding author. Department of Neurology, Johns Hopkins Hospital Pathology, 509 600 North Wolfe Street, Baltimore, MD 21287.
0733-8619/06/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.ncl.2005.11.001 synchronized fashion. Additionally, myoclonic movements may be sponta-neous or they may be activated by either movement or sensory stimulation.
Finally, myoclonus may be comprised of ‘‘positive’’ movements, in whicha burst of electromyographic activity is associated with the movement, ornegative movements, in which a brief pause of tonic muscular activity leadsto a jerk The causes of myoclonus are many. In 1963, however, Lance and Adams described four patients who developed severe myoclonus after surviving car-diac arrest . These patients initially developed a generalized myoclonusaccompanied by dysmetria, dysarthria, and ataxia. Over time, the myoclo-nus persisted but its character changed to a predominantly action myoclo-nus involving the limbs. Lance and Adams hypothesized that thisparticular constellation of symptoms observed after cardiac arrest was theresult of cerebral hypoxia Since this initial description, more than 40years ago, more than 100 patients who have had PHM have been reportedin the medical literature many of whom suffered hypoxia from car-diac arrest. Concordant with the initial descriptions by Lance and Adams,it is recognized that there are two types of PHM: acute PHM, which occurssoon after a hypoxic insult and is characterized by generalized myoclonus;and chronic PHM (Lance-Adams syndrome), which begins after a periodof delay and is manifested predominantly by action myoclonus.
Acute PHM occurs soon after a hypoxic episode and is characterized by severe, generalized myoclonic jerks in patients who are deeply comatose .
The jerks begin typically within the first 24 hours after hypoxia and oftenare characterized by violent flexion movements. When they persist formore than 30 minutes or occur for most of the first postresuscitation day,some term the abnormal movements, myoclonic status epilepticus (MSE), de-spite the lack of definitive evidence that these movements represent epilepticactivity. Posthypoxic MSE occurs in approximately 30% to 40% of comatoseadult survivors of cardiopulmonary resuscitation and is difficult to controland associated with a poor prognosis. In the largest published series of post-hypoxic MSE, Wijdicks and colleagues find that all 40 patients had intermit-tent generalized myoclonus involving both face and limb muscles. Stimuli,such as touch, tracheal suctioning, and loud handclaps, triggered myoclonicjerks in most of the patients. None of the 40 patients who had acute posthyp-oxic MSE awakened, improved in motor response, or survived Inanother review of 18 patients who had posthypoxic MSE, 14 patients diedwithin 2 weeks and the two patients who survived were left with profound dis-ability A meta-analysis of patients who had posthypoxic MSE paintsa similarly grim picture: of 134 pooled cases, 119 (88.8%) died, 11 (8.2%)remained in a persistent vegetative state, and 4 (3.0%) survived. Of the fourpatients who survived, two were described as having a good outcome MOVEMENT DISORDERS AFTER CARDIAC ARREST RESUSCITATION Clues to the pathophysiology of acute PHM arise from electrophysiologic and histopathologic studies. The electroencephalograms (EEGs) in these pa-tients are variable, but often display bursts of generalized spikes and poly-spikes or a burst suppression pattern, believed to be consistent with severeneuronal injury. On autopsy, patients who have acute posthypoxic MSEhave evidence of neuronal ischemia and cell death in the cerebral cortex,deep gray nuclei (ie, basal ganglia and thalamus), hippocampus, and cere-bellum Cortical damage is more severe in patients who have MSEthan in those who do not have myoclonus, however Because the sever-ity of cortical damage implies that the cortex may not be capable of gener-ating any activity, including myoclonic activity, it is postulated that acutePHM arises from a brainstem generator Treatment of myoclonic jerks in acute PHM is difficult and of question- able usefulness, particularly in the setting of posthypoxic MSE. Multiplemedications often are used, the most common of which are phenytoin, val-proate, and benzodiazepines. In one study of 18 patients who had posthyp-oxic MSE, 13 patients required intravenous anesthesetic agents, includingpropofol and midazolam Despite aggressive treatment of the myoclonicjerks, poor prognosis resulting from the severity of underlying brain injury isthe rule rather than the exception.
Chronic posthypoxic myoclonusdLance-Adams syndrome Chronic PHM, also known as Lance-Adams syndrome, typically occurs within a few days to a few weeks after hypoxic injury. In a series of 14 pa-tients who had chronic PHM, all but one were noted to have the onset ofmyoclonus while still in coma The myoclonus has several characteristicfeatures. Patients have an action myoclonus involving predominantly thelimbs. Myoclonic jerks commonly appear immediately on attempting tomove or position a limb and occasionally spread to other portions of thebody. The jerks generally disappear with relaxation of the limb. The preci-sion of the motor task seems to be proportional to the severity of myoclo-nus, making everyday tasks, such as bringing a cup to the mouth orgrasping a small object, extremely difficult . In addition, the myoc-lonus of chronic PHM has several other distinctive characteristics. In theirseries of 14 patients, Werhahn and colleagues report that 11 had stimulus-sensitive myoclonus Negative myoclonic jerks also contribute signifi-cantly to morbidity in patients who have chronic PHM. Postural lapses re-sulting from negative myoclonus predispose patients to frequent falls andoften result in patients being confined to wheelchairs Chronic PHM is a syndrome with diverse clinical, electrophysiologic, and neurochemical abnormalities , and the pathophysiology of this condi-tion is poorly understood. An example of the diversity of the disorder lies inthe nature of the myoclonus itself. The myoclonus in chronic PHM mayhave a cortical or subcortical origin. Clinical clues suggestive of a cortical origin include myoclonus that is distally predominant, highly action in-duced, and stimulus sensitive. A cortical origin for myoclonus also is sup-ported by electrophysiologic measures, such as enlarged somatosensoryevoked potentials and the gold standard, back-averaged EEG. Using suchmeasures, it seems that cortical myoclonus is much more common in chronicPHM than subcortical myoclonus, the latter of which tends to cause violentjerks of the proximal limbs and trunk . Patients who have chronic PHM,however, may suffer from cortical myoclonus, subcortical myoclonus, ora combination of the two, and there are no prognostic factors that can pre-dict which subtype of myoclonus a patient will develop.
The neurochemical and anatomic bases of chronic PHM remain unclear.
Several lines of evidence suggest that specific neurotransmitter abnormalitiesare involved in the pathogenesis of chronic PHM. Isolated reports demon-strate that low levels of 5-hydroxyindole amino acid (5-HIAA), a serotoninmetabolite, are present in the cerebrospinal fluid of patients who have PHMSome patients who have chronic PHM improve with administration ofthe serotonin precursor, 5-hydroxytryptophan (5-HTP) Further sup-port for a role of the serotonergic system in chronic PHM comes from an-imal models. Several groups demonstrate that, in rat models of PHM,myoclonus improves with 5-HTP treatment and severity of myoclonus cor-relates inversely with levels of striatal serotonin and cortical 5-HIAA. Inaddition, direct modulation of serotonin receptors affects PHM, as demon-strated in animal models in which the administration of agonists and certainantagonists of serotonin receptors can ameliorate PHM Another clue that serotonin signaling may be involved in the pathophys- iology of PHM lies in the finding that the majority of patients in the largestpublished series on PHM are female. A recent study examines the role of es-trogen in PHM and finds that estrogen treatment of female rats that wereovariectomized resulted in a significant increase in intensity and durationof PHM . It is hypothesized that estrogen, through its regulation of se-rotonergic activity, may influence the clinical course of PHM. Thus, it seemsthat although serotonergic modulation affects PHM, the relative contribu-tions of serotonin metabolism and of specific serotonin receptors to theoverall mechanisms of PHM remain unclear.
A recent report that describes marked exacerbation of chronic PHM in a patient administered trimethoprim-sulfamethoxazole (TMP-SMX) mayimplicate phenylalanine, a neurotransmitter precursor, in the pathogenesisof PHM. A patient who had high-grade non-Hodgkin’s lymphoma andchronic PHM whose myoclonus was well treated with oral piracetam devel-oped marked worsening of myoclonus on exposure to high-dose intravenousTMP-SMX. A reduction of the dosage of TMP-SMX resulted in a dramaticand rapid improvement of the myoclonic jerks The investigators believedit unlikely that alterations of renal or hepatic metabolism, or pharmacokine-tic or pharmacodynamic interactions between TMP-SMX and piracetam,accounted for the worsening of myoclonus; rather, they hypothesized that MOVEMENT DISORDERS AFTER CARDIAC ARREST RESUSCITATION TMP-SMX may have resulted in increased myoclonus by its well-describedaction of impairing phenylalanine metabolism and, thereby, elevating phenyl-alanine levels. Elevated phenylalanine levels, in turn, are linked to severalneurologic conditions. Unfortunately, neither serum nor cerebrospinal fluidphenylalanine levels were obtained to support this hypothesis.
Recently, radiologic tools have been used in an attempt to understand the anatomic and pathophysiologic basis of PHM. Seven patients who hadchronic PHM and EEG back averaging that demonstrated cortical myoclo-nus underwent fluorodeoxyglucose–positron emission tomographic scan-ning. Comparedwith control subjects, patients who had PHM exhibitedsignificant increases in glucose metabolism in several brain regions, includingthe ventrolateral thalamus Such findings may be compatible with the ratPHM model, in which the ventrolateral thalamic nucleus is implicated indi-rectly in the pathogenesis of PHM; Purkinje cell death occurs selectively inthe paravermal and vermal areas, which project mainly to the dorsolateralprotuberance of the fastigial nucleus and, in turn, to the ventrolateral thalamicnucleus Thus, there may be a link between the Purkinje cell death seen inPHM rats and the increased metabolic uptake observed by PET scanning inthe ventrolateral thalamic nucleus of humans who have PHM.
The treatment of chronic PHM can pose a challenge for several reasons. As previously alluded to, chronic PHM is a syndrome with diverse clinical pre-sentations likely stemming from varied pathophysiologies. In addition, the ef-fect of many drugs reported in the literature is given in qualitative fashion,providing only an approximation of an agent’s efficacy. Also, the small num-ber of patients who develop this syndrome obviates the possibility of large-scale clinical trials to evaluate the efficacy of antimyoclonic agents. Despitethese difficulties, a recent review of the literature, which includes more than100 cases of PHM, supports several important conclusions. Clonazepam, val-proate, and piracetam demonstrate significant efficacy in approximately 50%of patients in whom these agents were instituted. Therefore, the authors con-sider these to be first-line agents in the treatment of chronic PHM. A role for5-HTP also is supported by the authors’ recent literature review. 5-HTP re-sulted in marked or full improvement in 40% of patients in whom the effectwas reported; however, concomitant treatment with carbidopa often is neces-sary to prevent the severe nausea that accompanies administration of thisdrug. Several other drugs, including baclofen, diazepam, ethanol, and meth-ysergide, also are reported as efficacious in a limited number of patients. Ananalysis of these 122 cases reveals that there are several drugs that were re-ported to be not significantly efficacious in any case of chronic PHM; theseinclude phenytoin, primidone, phenobarbitol, and tetrabenazine Several newer agents also are reported to have efficacy in the treatment of chronic PHM. Levetiracetam, chemically related to piracetam, has beenstudied by several groups of investigators. Krauss and colleagues notethat one of two patients who had chronic PHM experienced substantial im-provement in myoclonus, whereas the other experienced some improvement with doses of 500 to 750 mg twice daily . Another study of the effects oflevetiracetam on myoclonus of different causes notes that rapid and sus-tained symptomatic improvement occurred only in a single patient whohad chronic PHM The authors also have studied the efficacy of levetir-acetam in PHM. They conducted an open-label, dose-escalation trial of thismedication in seven patients who had chronic myoclonus (including threewho had posthypoxic myoclonus) and showed that the mean Unified Myoc-lonus Rating Scale scores trended downward in every section after adminis-tration of levetiracetam, with significant decreases in the sections addressingpatient self-assessment and physician assessment of global disability .
Several reports describe patients who have PHM experiencing improve- ment of myoclonus with administration of alcohol Based on a previousreport that a patient who had alcohol-responsive myoclonus-dystonia hadsignificant improvement when treated with g-hydroxybutyric acid (GHB)the authors recently studied the efficacy of GHB in one patient whohad alcohol-responsive chronic PHM. Using an open-label, dose-finding,blinded-rater approach, they found that oral GHB was markedly effectivein ameliorating severe alcohol-sensitive PHM in this single patient Regardless of treatment, the majority of patients who have chronic PHM improve over time. Myoclonus, ataxia, and speech all tend to improve overseveral years, and disability scores reflective of the ability to ambulate, com-municate, and take care of themselves also improve In one series of 14patients who had chronic PHM, only four patients did not have an improve-ment in global disability score at a mean follow-up of 3.7 years . Althoughmany patients do experience significant improvement in symptoms, somewho have chronic PHM remain significantly disabled despite medical ther-apy. Currently, there are no well-accepted surgical options for such patients.
The authors hypothesize, however, that, given the ventral thalamic hyper-metabolism observed on PET scan in these patients and the fact that thala-motomy and thalamic stimulation are applied successfully to single patientswho have intractable myoclonus, stereotactic targeting of the ventrolateralthalamus using deep brain stimulation may be appropriate in some patientswho have severe, medication-refractory chronic PHM .
A variety of other movement disorders are observed after cerebral hypoxia, including parkinsonism, dystonia, chorea, athetosis, and tremor Al-though PHM may result from injury to the cerebellum or thalamus, manyof these other movement disorders are caused by damage of the basal ganglia.
Dystonia is one of the more common movement disorders to occur aftercerebral hypoxia and may develop in combination with an akinetic-rigid(parkinsonian) syndrome. This article discusses the clinical spectrum of post-hypoxic dystonic and akinetic-rigid syndromes and focuses on the pathophys-iology of basal ganglia dysfunction in these conditions.
MOVEMENT DISORDERS AFTER CARDIAC ARREST RESUSCITATION Dystonic and akinetic-rigid syndromes, alone or in combination, repre- sent a sizeable proportion of the posthypoxic movement disorders describedin the literature. Many of these cases are reported in patients surviving car-diac arrest. These syndromes may occur acutely, either at the time the hyp-oxic insult occurs or shortly thereafter, or more commonly in delayedfashion, months to years after the initial hypoxic insult The posthyp-oxic akinetic-rigid syndrome usually is a symmetric condition characterizedby various combinations of bradykinesia, micrographia, axial and appendic-ular rigidity, resting or postural tremor, and marked postural instabilityPosthypoxic dystonia can affect the limbs and face and often is asym-metric at onset with progression to a symmetric, generalized dystonia. Ina review of 12 patients who previously were normal and who suffered hyp-oxic ischemic insults of various causes, including cardiac arrest, Marsdenand colleagues note that six of the patients developed a pure dystonic syn-drome, two developed a pure akinetic-rigid syndrome, and four initially de-veloped an akinetic-rigid syndrome followed later by a dystonic syndromeThe akinetic-rigid syndrome developed typically within 3 months ofthe hypoxic event; after a rapid evolution, the majority of patients remainedclinically stable for many subsequent years. In contrast, the pure dystonicsyndrome developed, on average, 10 months after the hypoxic event, andprogressed gradually over several years. The majority of patients had visiblelesions in the basal ganglia on brain CT or MR imaging. Treatment ofakinetic-rigid symptoms with levodopa or dopamine agonists and adminis-tration of high-dose anticholinergic drugs for dystonic symptoms conferredlittle benefit to these patients.
Why do some patients who have basal ganglia lesions after cerebral hyp- oxia develop an akinetic-rigid syndrome, whereas others develop a predom-inantly dystonic syndrome? Marsden and colleagues note that the mean ageof the akinetic-rigid group at the time of anoxia was 41 years, whereas thatof the pure dystonic group was 13.5 years. Indeed, all six patients who de-veloped a pure dystonic syndrome were ages 21 years or less. This observa-tion led to the hypothesis that an age-dependent difference in the clinicalmanifestations of hypoxia exists, with younger people more prone to dysto-nia and older individuals more prone to an akinetic-rigid state Suchage-dependent differences also are observed in conditions, such as Parkinson’sdisease, in which early-onset patients are predisposed to dystonia. A mecha-nistic understanding of these observations, however, remains elusive.
The location of brain injury within the basal ganglia seems to be another factor that governs whether or not patients develop dystonia versus anakinetic-rigid state after cerebral hypoxia. Hawker and Lang, in their case se-ries of three patients who had suffered cerebral hypoxia, note that the two pa-tients who had primarily dystonic syndromes had lesions of the putamina onhead CT, whereas the patients who had an akinetic-rigid syndrome hadmarked bilateral lesions of the globus pallidus. Similar clinicoanatomicassociations are found in a wide variety of insults to the basal ganglia, including trauma, neurodegenerative diseases, and encephalitides Thishas led to the proposal that in the setting of hypoxia, lesions of the globuspallidus are responsible for the akinetic-rigid syndrome, whereas lesions ofthe putamen account for dystonia Further support for this hypothesisis provided by Marsden and colleagues, who find that dystonia is associatedwith putaminal injury in 10 of 14 cases and an akinetic-rigid syndrome is as-sociated with globus pallidus lesions in 11 of 14 cases. This association is notabsolute, however, as several examples of dystonia associated with pallidallesions and parkinsonism associated with putaminal lesions are noted Two other questions arise with respect to the pathophysiology of hypoxia- induced basal ganglia lesions. First, why are the basal ganglia so vulnerableto hypoxic insults? Two main hypotheses are put forth to explain this selec-tive vulnerability. The ‘‘vascular hypothesis’’ states that selective hypoperfu-sion results from the vascular supply of the basal ganglia and, in particular,the globus pallidus, underlies its susceptibility to hypoxic injury. The secondtheory is the ‘‘metabolic hypothesis,’’ which postulates that factors intrinsicto the striatum, such as intrinsically high oxidative metabolism or high den-sity of excitatory amino acid receptors, results in hypoxic damage .
Further studies are needed to determine whether or not vascular, metabolic,or other factors underlie the susceptibility of the basal ganglia to hypoxic in-jury. The second main question that arises is, how can a single exposure tocerebral hypoxia lead to the delayed onset and progression of symptomsyears later? Several mechanisms, including aberrant sprouting, synaptic reor-ganization, ephaptic transmission, and inflammatory changes, are suggestedas possible mechanisms of delayed symptomatology. Parallels with otherneurodegenerative diseases, in which excitotoxicity is followed by mitochon-drial dysfunction, oxidative stress, and eventual neuronal apoptosis, also arespeculated to play a role . Regardless of the mechanism, it seems thatdamage to the basal ganglia with preservation of the pyramidal system isa pathologic correlate of delayed posthypoxic dystonia or akinetic-rigidsyndromes It is difficult to predict precisely the final neurologic outcome from car- diac arrest and accompanying cerebral hypoxia. Although rare, severalmovement disorders may arise as a consequence of hypoxic injury, includingmyoclonus, dystonia, akinetic-rigid syndromes, tremor, and chorea. Dys-function of various portions of the central nervous system, includingthe basal ganglia, thalamus, midbrain, and cerebellum, is implicated in thepathogenesis of these posthypoxic movement disorders. The developmentof animal models of posthypoxic movement disorders and of newer imagingtechniques applied to human patients who have movement disorders afterhypoxic episodes has improved understanding of the pathophysiology ofposthypoxic movement disorders and has suggested newer treatments.
MOVEMENT DISORDERS AFTER CARDIAC ARREST RESUSCITATION Many outstanding questions remain, however. What factors promote sus-ceptibility to the development of posthypoxic movement disorders? Whydo patients who have similar clinical hypoxic insults develop markedly dis-similar movement disorders? Why are the basal ganglia especially vulnerableto cerebral hypoxia? Why do some movement disorders occur in delayedfashion and progress for years after the hypoxic insult? Is the pathogenesisof progressive posthypoxic movement disorders related to that of neurode-generative diseases? What are the most effective medications for the variousposthypoxic movement disorders? Is there a role for deep brain stimulationin the treatment of posthypoxic movement disorders? We anticipate thatcurrent and future research in the area of posthypoxic movement disorderswill reveal answers to some of these important questions.
[1] Fahn S. Posthypoxic action myoclonus: literature review update. Adv Neurol 1986;43: [2] Hawker K, Lang AE. Hypoxic-ischemic damage of the basal ganglia. Case reports and a re- view of the literature. Mov Disord 1990;5:219–24.
[3] Feve AP, Fenelon G, Wallays C, et al. Axial motor disturbances after hypoxic lesions of the globus pallidus. Mov Disord 1993;8:321–6.
[4] Bhatia KP, Marsden CD. The behavioral and motor consequences of focal lesions of the basal ganglia in man. Brain 1994;117:859–76.
[5] Govaerts A, Zandijcke MV, Dehaene I, et al. Posthypoxic midbrain tremor. Mov Disord [6] Fahn S, Marsden CD, Woert MHV. Definition and classification of myoclonus. Adv Neurol [7] Hallett M. Physiology of human posthypoxic myoclonus. Mov Disord 2000;15(Suppl 1): [8] Lance JW, Adams RD. The syndrome of intention or action myoclonus as a sequel to hypoxic encephalopathy. Brain 1963;86:111–36.
[9] Werhahn KJ, Brown P, Thompson PD, et al. The clinical features and prognosis of chronic posthypoxic myoclonus. Mov Disord 1997;12:216–20.
[10] Frucht S, Fahn S. The clinical spectrum of posthypoxic myoclonus. Mov Disord 2000; [11] Frucht SJ. The clinical challenge of posthypoxic myoclonus. Adv Neurol 2002;89:85–8.
[12] Wijdicks EFM, Prisi JE, Sharbrough FW. Prognostic value of myoclonus status in comatose survivors of cardiac arrest. Ann Neurol 1994;35:239–43.
[13] Hui ACF, Cheng C, Lam A, et al. Prognosis following postanoxic myoclonus status epilep- [14] Young GB, Gilbert JJ, Zochodne DW. The significance of myoclonic status epilepticus in postanoxic coma. Neurology 1990;40:1843–8.
[15] Fahn S. Posthypoxic action myoclonus: review of the literature and report of two new cases with response to valproate and estrogen. Adv Neurol 1979;26:49–82.
[16] Woert MHV, Rosenbaum D. L-5-hydroxytryptophan therapy in myoclonus. Adv Neurol [17] Truong DD, Matsumoto RR, Schwartz PH, et al. Novel rat cardiac arrest model of posthyp- oxic moclonus. Mov Disord 1994;9:201–6.
[18] Matsumoto RR, Aziz N, Truong DD. Association between brain indole levels and severity of posthypoxic myoclonus in rats. Pharmacol Biochem Behav 1995;50:553–8.
[19] Goetz CG, Vu TQ, Carvey PM, et al. Posthypoxic myoclonus in the rat: natural history, sta- bility, and serotonergic influences. Mov Disord 2000;15(Suppl 1):39–46.
[20] Truong DD, Kirby M, Kanthasamy A, et al. Posthypoxic myoclonus animal models. Adv [21] Kompoliti K, Goetz CG, Vu TQ, et al. Estrogen supplementation in the posthypoxic myoc- lonus rat model. Clin Neuropharm 2001;24:58–61.
[22] Jundt F, Lempert T, Dorken B, et al. Trimethoprim-sulfamethoxazole exacerbates post- hypoxic action myoclonus in a patient with suspicion of Pneumocystis jiroveci infection.
Infection 2004;32:176–8.
[23] Frucht SJ, Trost M, Ma Y, et al. The metabolic topography of posthypoxic myoclonus. Neu- [24] Welsh JP, Yeun G, Placantonakis DG, et al. Why do Purkinje cells die so easily after global brain ischemia? Aldolase C, EAAT4, and the cerebellar contribution to posthypoxic myoc-lonus. Adv Neurol 2002;89:331–59.
[25] Krauss GL, Bergin A, Kramer RE, et al. Suppression of posthypoxic and postencephalitic myoclonus with levetiracetam. Neurology 2001;56:411–2.
[26] Lim LL, Ahmed A. Limited efficacy of levetiracetam on myoclonus of different etiologies.
[27] Frucht SJ, Louis ED, Chuang C, et al. A pilot tolerability and efficacy study of levetiracetam in patients with chronic myoclonus. Neurology 2001;57:1112–4.
[28] Genton P, Guerrini R. Effect of alcohol on action myoclonus in Lance-Adams syndrome and progressive myoclonic epilepsy. Mov Disord 1992;7:92.
[29] Jain S, Jain M. Action myoclonus (Lance-Adam syndrome) secondary to strangulation with dramatic response to alcohol. Mov Disord 1992;6:183.
[30] Priori A, Bertolasi L, Pesenti A, et al. Gammahydroxybutyric acid for alcohol-sensitive my- oclonus with dystonia. Neurology 2000;54:1706.
[31] Frucht SJ, Bordelon Y, Houghton WH. Marked amelioration of alcohol-responsive posthyp- oxic myoclonus by gamma-hydroxybutyric acid (Xyrem). Mov Disord 2005;20:745–51.
[32] Burke RE, Fahn S, Gold AP. ‘‘Delayed-onset dystonia in patients with ‘‘static’’ encephalop- athy. J Neurol Neurosurg Psychiatry 1980;43:789–97.
[33] Bhatt MH, Obeso JA, Marsden CD. Time course of postanoxic akinetic-rigid and dystonic syndromes. Neurology 1993;43:314–7.
[34] Kuoppamaki M, Bhatia K, Quinn N. Progressive delayed-onset dystonia after cerebral an- oxic insult in adults. Mov Disord 2002;17:1345–9.
[35] Scott BL, Jankovic J. Delayed-onset progressive movement disorders after static brain [36] Boylan KB, Chin JH, DeArmond SJ. Progressive dystonia following resuscitation from car- diac arrest. Neurology 1990;40:1458–61.

Source: http://aocpmr.org/wp-content/uploads/2012/12/Movement-Disorders-after-Resuscitation-from-Cardiac-Arrest.pdf