NEUROLOGICAL REVIEW SECTION EDITOR: DAVID E. PLEASURE, MD Movement Disorders Emergencies Part 1 Hypokinetic Disorders Bradley J. Robottom, MD; William J. Weiner, MD; Stewart A. Factor, DO ovement disorders usually do not require emergent intervention; nevertheless, there are acute/subacute clinical settings in which the neurologist is consulted. It is in these circumstances that the neurologist must be prepared to accurately diagnose and properly treat the patient. We have reviewed the literature regarding move- Mment disorder emergencies and divided them into hypokinetic (part 1) and hyperkinetic (part 2) presentations. In part 1, drug-induced syndromes including neuroleptic malignant syndrome, par- kinsonism hyperpyrexia syndrome, and serotonin syndrome will be discussed. Emergency com- plications related to the management of Parkinson disease, including falling, motor fluctuations, and psychiatric issues, will also be reviewed. Arch Neurol. 2011;68(5):567-572 Movement disorders often have an insidi- DRUG-INDUCED MOVEMENT ous onset and slow progression and are not DISORDER EMERGENCIES often associated with emergency situa- tions. However, neurologists may be called Neuroleptic Malignant Syndrome on to diagnose and treat evolving move- ment disorders or acute complications of Neuroleptic malignant syndrome, first de- existing diseases in the emergency depart- scribed in 1960,2 is an iatrogenic disorder re- ment or intensive care unit. Such situa- sulting from exposure to drugs that block tions meet the working definition of an dopamine receptors. While most cases are “emergency,” a rapidly evolving disorder caused by neuroleptics (both typical and (hours to days) in which the failure to di- atypical,evenclozapine),3-6 othermedications agnose and treat may lead to significant such as prochlorperazine, metoclopramide morbidity or mortality.1 This review is di- hydrochloride, droperidol, and prometha- vided into 2 parts based on phenomenol- zine hydrochloride are also implicated.7 ogy, hypokinetic and hyperkinetic disor- Diagnostic criteria integrating clinical and ders, and it discusses rapidly evolving laboratory features (Table 1) have been de- situations that require emergency inter- veloped.8 Because the incidence of NMS is vention. A number of the disorders dis- low, 0.2%,9 a high index of suspicion is nec- cussed are rare. Data regarding preva- essary to make the appropriate diagnosis. lence and incidence have not been Neuroleptic malignant syndrome is impor- evaluated. In part 1, we review hypoki- tant to consider in any patient with acute- netic disorders including the drug- onset parkinsonism and fever because it is induced movement disorder emergen- life threatening (mortality rate of 5%-20%). cies neuroleptic malignant syndrome Young and middle-aged men appear to be at (NMS), parkinsonism-hyperpyrexia syn- higher risk.10 drome (PHS), and serotonin syndrome Neurolepticmalignantsyndromeisaclini- (SS) as well as emergent complications of calsyndromecomprisingfever,rigidity,men- Parkinson disease (PD). talstatuschange,autonomicdysfunction,and other movement disorders (tremor, dysto- Author Affiliations: Department of Neurology, University of Maryland School of nia, and myoclonus) (Figure 1). Key labo- Medicine, Baltimore (Drs Robottom and Weiner); and Movement Disorders ratoryabnormalitiesincludeleukocytosisand Program, Emory University School of Medicine, Atlanta, Georgia (Dr Factor). elevated creatine kinase level. Additionally, ARCH NEUROL / VOL 68 (NO. 5), MAY 2011 WWW.ARCHNEUROL.COM 567 ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 acute-phase reactants, including albumin and serum iron drome occurs in patients with PD who abruptly withdraw levels, are decreased.11 Symptoms often begin after initia- or reduce dopaminergic medications. It was first reported tion or an increase in neuroleptic dose.5 Neuroleptic malig- in the context of abrupt discontinuation of antiparkinso- nant syndrome increases in severity over 48 to 72 hours and nian medications during “levodopa holidays” in the lasts 7 to 14 days. Medical complications can be chronic and 1980s.16,17 While levodopa holidays are no longer recom- irreversible including renal failure from rhabdomyolysis, mended, patient noncompliance or abrupt changes in medi- respiratory failure from decreased chest wall compliance, cation replicate that scenario. Aggressive medication ad- aspiration pneumonia, and other complications of immo- justments are not uncommon, particularly after deep brain bility such as deep venous thrombosis and pressure ulcers. stimulation surgery in PD. Clinicians must realize that PHS Pulmonaryembolism,pneumonia,orrenalfailuremayresult is a potential complication and that deep brain stimula- in death. tion surgery does not protect the patient from PHS.18 De- No prospective randomized trials exist in NMS. Key steps hydration and metabolic disturbances may also precipi- in treatment include withdrawal of the causative agent and tate it.19 Treatment involves supportive measures and treatmentwithdopaminergicagents.Bromocriptinemesylate reinstituting dopaminergic therapy. Bromocriptine and dan- has been used most often and is considered the drug of trolene may be added as additional therapy. High-dose in- choice12; however, other dopaminergic agents are equally travenous methylprednisolone has been proposed as ad- effective. Dantrolene sodium, a nonspecific muscle relax- junctive therapy, and it appears to be effective based on 1 ant, reduces muscular rigidity and minimizes rhabdomyoly- small randomized trial.20 Despite treatment, permanent sisifthedopaminergicagentdoesnotreversethesymptoms.13 worsening of PD and fatalities have been reported.21 Combinationtherapyhasbeenfoundtobesafeandeffective,12 and treatment should continue for 7 to 10 days depending Serotonin Syndrome on the half-life of the causative agent. One-third of patients may relapse if neuroleptic treatment is restarted too early, Any drug that enhances serotonergic transmission can so waiting at least 2 weeks after NMS has cleared is good prac- precipitate SS, which has the core clinical features of fe- tice.14 In patients who require immediate treatment of psy- ver, myoclonus, and altered mental status.22 Serotonin chosis, electroconvulsive therapy has been successful.15 syndrome was first described in 1960 in patients receiv- ing monoamine oxidase inhibitor monotherapy23 but is Parkinsonism-Hyperpyrexia Syndrome now encountered in patients taking 2 or more drugs with serotonergic actions (tricyclic antidepressants or selec- Parkinsonism-hyperpyrexia syndrome may be indistin- tive serotonin reuptake inhibitors in combination with guishable from NMS except that it occurs in patients with nonselective monoamine oxidase inhibitors)24 (Table 2). preexisting parkinsonism. Parkinsonism-hyperpyrexia syn- Many of the clinical features overlap with NMS (Table 3); however, SS may have additional clinical features such as myoclonus, hyperreflexia, seizures, and mood alter- Table 1. Diagnostic Criteria for Neuroleptic ation (restlessness, elevated mood).26 This overlap may a Malignant Syndrome relate to the impact elevated serotonin levels have on low- ering dopamine levels. Treatment consists of discontinu- Criteria Feature ation of the causative agent, supportive therapy, and Major Fever, rigidity, and elevated creatine kinase level cyproheptadine hydrochloride for severe cases. Cypro- Minor Tachycardia, abnormal blood pressure, tachypnea, heptadine, an antihistamine and serotonin antagonist, is altered consciousness, diaphoresis, and leukocytosis given in divided doses up to a maximum dose of 32 mg/ d.27 Serotonin syndrome may resolve quickly25 or is po- a The presence of all 3 major, or 2 major and 4 minor, criteria indicates a high likelihood of neuroleptic malignant syndrome in the appropriate clinical tentially fatal. Like NMS and PHS, the rarity and seri- context. ousness of SS precludes large randomized trials. A B Figure 1. Jaw-opening dystonia (trismus) (A) and hand dystonia (B) secondary to neuroleptic malignant syndrome. ARCH NEUROL / VOL 68 (NO. 5), MAY 2011 WWW.ARCHNEUROL.COM 568 ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 Table 2. Drugs Reported to Cause Serotonin Syndrome Table 3. Comparison of Neuroleptic Malignant Syndrome and Serotonin Syndromea Drug Neuroleptic Serotonin Monoamine oxidase inhibitors Malignant Syndrome Syndrome Selective serotonin reuptake inhibitors Serotonin-norepinephrine reuptake inhibitors Onset Acute Subacute (days) Tricyclic antidepressants (minutes to hours) L-tryptophan Resolution Gradual (average 9 d) Improves in Ͻ24 h Buspirone hydrochloride Physical Altered sensorium Altered sensorium Opiates (except morphine) examination (Ͼ90%) (50%) Lithium Muscle rigidity Muscle rigidity Ͼ Triptans ( 90%) (50%) 3,4-Methylenedioxymethamphetamine (ecstasy) Autonomic Autonomic Ͼ Lysergic acid diethylamide dysfunction ( 90%) dysfunction Hyperthermia (50%-90%) Amphetamines (Ͼ90%) Hyperthermia (50%) Cocaine Hyperreflexia (50%) Myoclonus (50%) Laboratory Elevated creatine Elevated creatine PARKINSONISM abnormalities kinase level (Ͼ90%) kinase level (Ͻ20%) Elevated hepatic Elevated hepatic Emergency Department Admissions in PD transaminase levels transaminase levels (Ͼ75%) (Ͻ10%) Leukocytosis Leukocytosis Parkinson disease is a neurodegenerative disorder charac- (Ͼ90%) (Ͻ15%) terized by tremor, rigidity, bradykinesia, and postural