REVIEW URRENT C OPINION
Movement disorders emergencies Renato P. Munhoz a, Laura M. Scorr b, and Stewart A. Factor b
Purpose of review Although movement disorders are traditionally viewed as chronic diseases that are followed electively, a growing number of these patients present with acute, severe syndromes or complications of their underlying neurological problem. Identifying and managing movement disorders emergencies is challenging, even for the specialist. This review summarizes evidence outlining the clinical presentation of acute, life-threatening movement disorders. Recent findings We review the most significant aspects in the most common movement disorders emergencies, including acute complications related to Parkinson’s disease and parkinsonism, serotonergic, and neuroleptic malignant syndromes, chorea, ballismus, dystonia, myoclonus, and tics. Summary The increasing amount of information delineating the descriptions of movement disorders emergencies provides means for more effective prevention, identification, and management for the nonspecialist. Although the commonest of these syndromes eventually have a good outcome, serious conditions such as neuroleptic malignant syndrome and status dystonicus may induce substantial rates of morbidity and mortality. This review re-emphasizes the need for their prompt identification and management. Keywords movement disorders emergencies, neuroleptic malignant syndrome, serotonergic syndrome, status dystonicus
INTRODUCTION Movement disorders encompass disabling syndromes typically viewed as a realm of inexorably progressive chronic disorders that are, in most cases, followed and treated in ambulatory care settings. More recently, this view has been challenged by the growing body of literature as well as clinical experience showing that movement disorders can also present acute and more aggressively [1]. The concept of movement disorders emergencies has been coined to address such situations, as a neurological disorder evolving acute or subacutely, in which the clinical presentation is dominated by movement disorders and in which failure to accurately diagnose and manage the patient may result in significant morbidity or even mortality. Here, we used these criteria to concisely review diagnostic approaches to movement disorders emergencies by identifying the phenomenology according to the predominant abnormal movement pattern, describing common causes and therapeutics.
EMERGENCIES IN PARKINSON’S DISEASE Severe motor fluctuations Motor fluctuations in Parkinson’s disease typically are not severe enough to need urgent interventions; www.co-neurology.com
however, some patients may present extremely disturbing and dramatic ‘off’ periods, especially when they occur suddenly, associated with prominent akinesia, dysautonomia, and psychiatric features, such as anxiety and panic. In these instances, history should look for potential triggers or aggravating factors, including infections, dopaminergic medication changes, and inclusion of antidopaminergic drugs. Management involves combined approaches: fragmentation of daily doses of levodopa, crushed tablets, controlled-release or dispersible levodopa, subcutaneous dopamine agonists, monoamine oxidase B (MAO-B) and catechol-Omethyltransferase (COMT) inhibitors, and elective stereotactic surgery [2].
a Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada and bDepartment of Neurology, Emory University School of Medicine, Emory University, Atlanta, Georgia, USA
Correspondence to Renato P. Munhoz, Movement Disorders Centre, Toronto Western Hospital, 399 Bathurst Street, McL7-419, Toronto, ON M5T 2S8, Canada. Tel: +1 416 603 5800 x5214; fax: +1 416 603 5004; e-mail: [email protected] Curr Opin Neurol 2015, 28:406–412 DOI:10.1097/WCO.0000000000000212 Volume 28 Number 4 August 2015
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Movement disorders emergencies Munhoz et al.
Acute parkinsonism/acute worsening of parkinsonism
KEY POINTS Neuroleptic malignant syndrome, serotonergic syndrome, and malignant hyperthermia are lifethreatening emergencies with sometimes subtle clinical presentations that can be distinguished based on history of drug exposure. In Parkinson’s disease, acute psychosis or worsening of the motor features are usually associated with or triggered by concurrent medical conditions such as infections, metabolic disturbances, or neurological disorders. Acute parkinsonism has a relatively broad differential diagnosis; however, most cases are drug induced, often related to high potency DRBs in parenteral formulations. Status dystonicus is a potentially fatal and unusual complication of dystonia that often requires prompt, complex, and aggressive interventions, although no formally established management guidelines exist.
Acute severe de-novo parkinsonism is uncommon, most frequently caused by exposure to potent dopamine receptor blockers (DRBs), such as neuroleptics and antiemetics. Other rare causes include hypoxic– ischemic encephalopathy, intoxications, acute hydrocephalus, and infections [3,5 ,6]. Table 1 lists the broader differential diagnosis. Acute worsening of motor symptoms in Parkinson’s disease, unrelated to disease progression, typically occurs because of concurrent medical conditions, such as urinary or respiratory tract infections, metabolic disturbances, or neurological disorders (subdural hematoma, spinal cord lesion, brain tumor, etc.) [1,3,7]. &
Table 1. Differential diagnosis for acute parkinsonism Cause Drug induced Neuroleptics Antiemetics
Parkinsonism–hyperpyrexia and dyskinesia– hyperpyrexia syndromes Parkinsonism–hyperpyrexia syndrome (PHS) mimics neuroleptic malignant syndrome (NMS) in patients with Parkinson’s disease [3]. It is characterized by hyperthermia, dysautonomia, altered consciousness, severe rigidity, and elevated serum creatine kinase levels. PHS may be triggered by infections, hot weather, dehydration, and, particularly, reduction or withdrawal of antiparkinsonian agents (levodopa, dopamine agonists, and amantadine). Commonest situations in which PHS occurs in the context of dopaminergic treatment discontinuation include noncompliance, hospital admission due to comorbidities, or as part of the preoperative procedure for stereotactic surgery. Interestingly, recurrent PHS was described after discontinuation of subthalamic nucleus deep brain stimulation. Potentially fatal complications include venous thrombosis, pulmonary embolism, aspiration pneumonia, and renal failure. Treatment is based on supportive measures and reinstitution of adequate dopaminergic therapy. Occasionally, dantrolene is necessary [3]. Dyskinesia–hyperpyrexia syndrome (DHS) consists of severe dyskinesias leading to muscle exhaustion, rhabdomyolysis, hyperthermia, and confusion. It shares some of the features of PHS; however, dyskinesias – not rigidity – predominate. In addition, DHS, contrarily to PHS, should be treated by cautiously reducing the dosage of dopaminergic drugs [4 ]. &
Anticonvulsants Cytotoxic agents Antidepressants Intoxications Carbon monoxide Methanol Organophosphates 1-Methyl-1–4-phenyl-4-proprionoxypiperidine (MPTP) Manganese Cyanide Disulfiram Structural Subdural hematoma Hydrocephalus Strategic ischemic lesions Tumors Infections/postinfectious/inflammatory Viral encephalitis HIV Postinfectious Autoimmune Metabolic Pontine and extrapontine myelinolisis Diabetic uremia Hepatic encephalopathy Genetic Rapid-onset dystonia parkinsonism Acute decompensation in Wilson’s disease Functional
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For both acute situations, treatment should be focused on resolution of underlying etiologic processes. Occasionally, symptomatic treatment with dopaminergic agents is required [8].
Acute psychosis in Parkinson’s disease Psychosis occurs in up to half of cases with Parkinson’s disease throughout the disease course, frequently associated and triggered by the same agents used to treat the motor symptoms; however, acute clinical conditions (infectious, metabolic, or neurological disorders) may play a role [8,9]. Manifestations include visual hallucinations, delusions, confusion, and agitation. After treatment of potential comorbidities, a stepwise withdrawal of potentially contributing agents is recommended, starting with anticholinergics, followed by MAO-B inhibitors, dopamine agonists, amantadine, and COMT inhibitors. Introduction of an antipsychotic (clozapine or quetiapine) may be necessary [3,5 ,8]. &
Neuroleptic malignant syndrome NMS is an idiosyncratic abrupt reaction to DRB [10]. Often, agents include ‘classic’ neuroleptics; however, newer ‘atypical’ agents have all also been implicated, the safest being clozapine and quetiapine [11 ]. In addition, NMS can occur with other &&
dopamine-blocking drugs or as PHS, after abrupt withdrawal of dopaminergic agents [1,3,12 ,13]. Usually, symptoms start during the first 2 weeks of treatment initiation or dosage change [14]. Risk factors include abrupt dose escalation, depot formulations, male sex, young age, use of lithium and selective serotonin reuptake inhibitors (SSRIs), high temperatures, dehydration, exhaustion, extrapyramidal syndromes, and previous NMS episode (Table 2) [15]. All age groups can be affected, most cases are in their fourth and fifth decades [10,12 ,15]. Mortality remains high between 20 and 30% of cases [1,3]. Most survivors recover without sequelae; however, some present cognitive and motor abnormalities, including rigidity, tremor, and dystonia [16]. Diagnostic criteria combine the tetrad of hyperthermia, rigidity, altered mental status, and dysautonomia. Associated signs include tremor, dystonia, chorea, myoclonus, seizures, ataxia, hyporeflexia, and extensor plantars [3,10,12 ]. In addition, laboratory changes include raised serum creatine kinase (>1000 IU/l), impaired liver, renal, and coagulation status tests, leukocytosis, electrolyte disturbances, proteinuria, rhabdomyolysis, and myoglobinuria [1,10,12 ]. The most important differential diagnoses are serotonergic syndrome, malignant hyperthermia, and catatonia [1,12 ,13]. Treatment depends on recognition, exclusion of differential diagnoses, medication withdrawal, &&
&&
&&
&&
&&
Table 2. Comparison of features and management of neuroleptic malignant syndrome, serotonergic syndrome, and malignant hyperthermia Neuroleptic malignant syndrome
Serotonergic syndrome
Malignant hyperthermia
Age/sex prodisposition
Young men
None
Children, young adults
Triggering factor
Idiosyncratic
Drug combination/ overdose
Gene mutation
Onset
Acute
Subacute
Acute
Causative agents
Classic/newer antipsychotics, antiemetics, L-dopa withdrawal
SSRIs, SNRIs, tricyclic antidepressants, MAOIs, L-tryptophan, amphetamines, cocaine
Volatile anesthetics, succinylcholine
Fever
þþþ
þþ
þþþ
Confusion
þþþ
þþþ
þ
Dysautonomia
þþþ
þþþ
þþþ
Motor features
Tremor, rigidity
Myoclonus, rigidity, stereotypies, hyperreflexia
Rigidity
Diaphoresis
þþþ
þþ
þþþ
Elevated serum creatine kinase
þþþ
þþ
þþþ
Elevated serum transaminases
þþþ
þ
Metabolic acidosis
þ
þ
þþ
Pharmacologic treatmenta
Bromocriptine, amantadine, dantrolene
Cyproheptadine, methylsergide
Dantrolene
MAOIs, monoamine oxidase inhibitors; NMS, neuroleptic malignant syndrome; SNRIs, serotonin–norepinephrine inhibitors; SSRIs, selective serotonin reuptake inhibitors. a Prior to any form of pharmacological treatment, patients should be stabilized and withdrawn of causative agent.
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Movement disorders emergencies Munhoz et al. Table 3. Differential diagnosis of acute chorea and ballismus Vascular
Ischemic/hemorrhagic stroke Malformations Postpump chorea Polycythemia vera Nonketotic hyperglycemia Hypoglycemia Uremic encephalopathy Hyperthyroidism Hypoparathyroidism
Structural
Basal ganglia lesion or mass Cerebellar lesion or mass Thalamotomy or subthalomotomy
Infectious
Cryptococcal granuloma Toxoplasmosis Tuberculoma HIV encephalitis
Autoimmune
Postinfectious/Sydenham chorea/ chorea gravidarum Systemic lupus erythematosus Antiphospholipid antibody syndrome Scleroderma Behcet disease Polyarteritis nodosa Sarcoidosis Multiple sclerosis Paraneoplastic (CV2/CRMP-5 antibodies)
Iatrogenic
Serotonergic syndrome results most often from the combination of two or more agents that enhance serotonergic activity or concentration in the central nervous system [1,3,12 ,18]. This underrecognized syndrome presents with agitation, mental status changes, myoclonus, ataxia, postural instability, hyperreflexia, rigidity, and dysautonomia after changes in serotonergic drug regimen [1,19]. Onset is typically abrupt but some patients report insidious or recurrent subtle cognitive decline, behavioral abnormalities, and tremor with postural changes days to weeks before the full-blown syndrome develops [18]. Serotonergic syndrome is a predictable reaction. The offending drugs are those that cause excessive brainstem and spinal cord serotonin or 5-hydroxytryptamine (5-HT) type 1A receptor stimulation [18,20]. The most common implicated agents are listed in Table 2, but although any of them can potentially cause serotonergic syndrome, a combination is usually needed, with greater risk for monoamine oxidase inhibitors or SSRIs concomitantly used with any other serotonergic agent [18]. Although doses taken are commonly within therapeutic limits, 20% of cases occur secondary to overdose [1,21]. Other risky circumstances include rapid titration, addition or switch to a new agent without proper washout period, liver or renal disease, endogenously reduced monoamine oxidase A activity, cytochrome P4502D6 enzyme inhibition, and old age [19]. Serum or cerebrospinal fluid serotonin levels are useless for diagnosis, which is established on clinical grounds [12 ,18]. The starting point is obviously the history of medication exposure, added by clinical manifestations. The most widely used diagnostic criteria require the positive medication history along with any of the following: myoclonus, agitation or diaphoresis; unexplained hyperthermia; hypertonia; and tremor and hyperreflexia, after other causes have been ruled out [22]. Seizures, renal failure, and coagulopathy may occur [1,3,18,20]. Laboratory abnormalities include metabolic acidosis, rhabdomyolysis, elevated white cell count, and serum aminotransferase and creatinine levels. Differential diagnoses include cocaine or lithium overdose, anticholinergic poisoning, malignant hyperthermia, and NMS, each readily distinguished from serotonergic syndrome based on medication exposure history [12 ,19,22]. Treatment requires medication withdrawal, enough to improve half of all cases [1,3]. Persistent/severe symptoms require pharmacologic treatment. Nonspecific 5-HT receptor blockers (cyproheptadine and methysergide) have been &&
Cerebral anoxia
Metabolic
Serotonergic syndrome
Anticonvulsants Oral contraceptives Levodopa
&&
Cocaine Amphetamines Morphine Methadone Alcohol
supportive care, and pharmacological interventions depending on severity and presence of complications [1,3,10]. Severe symptoms require intensive care management and pharmacological reduction of rigidity (benzodiazepines or dantrolene) and dopaminergic blockage (bromocriptine or levodopa), as well as control of agitation [10,12 ,13]. Electroconvulsive therapy has been used anecdotally [17]. Neuroleptics should be stopped for at least 2 weeks after the acute phase. Management of the underlying psychiatric condition can be then restarted with low doses, slow titration, avoiding lithium, and with close observation to prevent recurrence [1,10]. &&
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Movement disorders Table 4. Pharmacological treatment of movement disorders Movement disorder
Medication class
Medication
Initial – maximum daily dose (mg)
Chorea
Neuroleptic
Haloperidol
0.5–8
Risperidone Dopamine-depleting agent
Ballism Myoclonus
Tics
0.5–6
Tetrabenazine
12.5–75
Benzodiazepine
Clonazepam
0.5–6
Anticonvulsant
Valproic acid
750–1500 12.5–200
Dopamine-depleting agent
Tetrabenazine
Neuroleptic
Haloperidol
Anticonvulsant
Levetiracetam
500–3000
Valproic acid
750–1500
Benzodiazepine
Clonazepam
0.5–6
Neuroleptic
Pimozide
1–10
Haloperidol
0.5–8
Risperidone
0.5–6
Dopamine-depleting agent Antihypertensives
0.5–8
Tetrabenazine
12.5–75
Clonidine
0.1–0.6
Guanfacine Dystonic storm
Anticholinergic
1–3
Trihexyphenidyl
5–20
Diphenhydramine Dopamine blocker
25–400
Haloperidol
0.5–8
Pimozide Acute dystonic reaction
1–10
Dopamine-depleting agent
Tetrabenazine
12.5–75
Anticholinergic
Benzotropine
1–6
Diphenhydramine
credited with shortening the syndrome’s duration [1,23]. Other agents include benzodiazepines, chlorpromazine, and propranolol. Treatment of seizures, arrhythmias, coagulopathy, rigidity, and hyperthermia may be necessary [23]. Serotonergic syndrome is potentially fatal, mortality rates range from 2.4 to 12% [20,21]. As in NMS, reintroduction of treatment of the underlying psychiatric disorder requires close monitoring, low dose, and slow titration [19,21].
Malignant hyperthermia Malignant hyperthermia is a rare genetic muscle disorder that occurs when a mutation-positive patient is exposed to inhalation anesthetics or depolarizing muscle relaxants [24]. Malignant hyperthermia manifests with abrupt hyperthermia, fluctuations in blood pressure, hypercarbia, hyperkalemia, metabolic acidosis, rigidity, and rhabdomyolysis [25 ]. Malignant hyperthermia results from uncontrolled calcium flux across muscle membrane, in more than half of cases due to a dominant mutation on the gene encoding skeletal muscle type-1 ryanodine receptor [26]. Dantrolene can be effective &
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25–400
treatment, along with correction of metabolic and electrolyte abnormalities. At present, with appropriate management and awareness, mortality is less than 5% [24,25 ]. Comparison of NMS, serotonergic syndrome, and malignant hyperthermia is shown in Table 2. &
Chorea and ballismus Acute severe chorea can result from numerous causes including drug exposures, toxic/metabolic derangements, vascular disease, infectious/postinfectious, and autoimmune disorders, leading to hyperthermia and rhabdomyolysis if not recognized and treated aggressively. Sydenham chorea is a childhood-onset manifestation of rheumatic fever [27]. Additional features include behavioral changes, weakness, hypotonia, and vocalizations. The diagnosis is clinical with supportive laboratory tests often showing elevated a-streptolysin-O and a-DNAase-B titers [28]. The most widely used symptomatic treatment of chorea under these circumstances is valproic acid at doses of 10–25 mg/kg/day. DRB should be reserved for severe and refractory cases because of the associated Volume 28 Number 4 August 2015
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Movement disorders emergencies Munhoz et al.
risk of complications [27,28]. Chorea gravidarum has been historically associated with a past history of rheumatic fever or Sydenham chorea, but chorea arising during pregnancy can also be drug induced or associated with systemic lupus erythematosus, antiphospholipid antibody syndrome, syphilis, and encephalitis [29]. In the case of classic chorea gravidarum, chorea typically begins in the first trimester. One-third of cases resolve spontaneously before delivery, and the remainder within hours after delivery. When necessary, after the first trimester, low-dose haloperidol has been shown to be effective [27,29]. Ballism defines larger amplitude, coarse, forceful movements often occurring acute and unilaterally. Ballism and chorea may in fact represent a continuum of hyperkinetic movements differentiated by speed and amplitude [30]. The most common cause of hemiballism is vascular, classically taught to indicate a lesion to the contralateral subthalamic nucleus. However, this topography is uncommon and lesions in multiple areas have been implicated [31,32]. Nonketotic hyperglycemia can result in unilateral or bilateral ballism, typically in elderly females, as a presenting feature of diabetes mellitus or in established cases [32,33]. Brain MRI T1weighted images typically show high signal in the contralateral putamen and occasionally in the globus pallidus, findings thought to result from petechial hemorrhages [33]. Abnormal movements tend to subside when the metabolic disturbance normalizes, but may be permanent. Other causes of acute ballism and chorea are listed in Table 3. Most cases resolve spontaneously within months. Table 4 shows treatment options when required. Treatment-refractory patients may need stereotactic surgery [5 ]. &
Dystonia Patients with inherited, acquired, or idiopathic dystonia can develop acute worsening with severe, continuous contractures, a phenomenon referred to as ‘dystonic storm’ or status dystonicus. Several factors can precipitate status dystonicus including infection, medication changes, and trauma [34,35]. As the sustained contractures can be life threatening, ICU admission is necessary, in addition to a stepwise pharmacological approach that includes anticholinergics, DRB, dopamine depletors, sedation, and paralyzing agents. In refractory status dystonicus, stereotactic surgery has been tried [35]. Acute dystonic reactions can be seen after exposure to DRB, typically within 24 h of exposure. Risk is increased in men and when the dose is rapidly titrated [1,30]. Manifestations can combine
blepharospasm, cervical, laryngeal or limbs dystonia, and oculogyric crisis. Life-threatening respiratory compromise can occur when the larynx or pharynx are affected. Management includes parenteral anticholinergics or antihistamines, after the precipitating agent is discontinued [1].
Myoclonus Myoclonus can present emergently, especially in the inpatient setting, and be a harbinger of an underlying toxic metabolic derangement, drugs reaction (as in serotonergic syndrome and NMS), or cerebral hypoxia. Two myoclonic syndromes can result from cerebral anoxia: myoclonus status epilepticus (MSE) and Lance Adams syndrome (LAS) [36 ,37]. MSE usually indicates poor prognosis and begins within hours of the anoxic event with spontaneous, unrelenting, generalized, or multifocal myoclonus in comatose patients [36 ]. LAS or postanoxic myoclonus has a delayed onset, with stimulus sensitive and action-induced movements [37]. LAS may improve spontaneously over years or be unrelenting. When myoclonus is particularly disabling, treatment may include clonazepam, valproic acid, and levetiracetam (Table 4) [30]. Finally, myoclonus may be a drug reaction induced by the same agents that cause serotonergic syndrome and NMS, added by opiates, gabapentin, antibiotics, and spinal anesthetics. &
&
Tics Although the majority of patients with tic disorders have a benign course, neurologic injury due to intense exacerbation may be an uncommon emergency, including cases in which head thrusting with violent neck movements resulted in compressive neuropathies, myelopathies, and subdural hematoma [38]. Factors known to markedly worsen tics include fatigue, stress, infection, and medications (stimulants, tricyclic antidepressants, and SSRIs). After the precipitating factor has been removed, pharmacologic treatment may be necessary using neuroleptics and dopamine depleting agents [30].
CONCLUSION The scope of the movement disorders provided in this review was intended to focus on life-threatening syndromes that diverge from the archetypal potentially severe but chronic, insidious disorders seen on most specialized ambulatory care clinics. Some of them have uncertain diagnostic criteria and are managed using an assemblage of anecdotal treatment options. These disorders may, therefore,
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present as sources diagnostic confusion and treatment dilemmas in emergency settings. Future directions should be directed not only to advance the basic and clinical aspects of these disorders but also to disseminate means for more accurate and prompt diagnosis and interventions. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Munhoz RP, Moscovich M, Araujo PD, Teive HA. Movement disorders emergencies: a review. Arq Neuropsiquiatr 2012; 70:453–461. 2. Giugni JC, Okun MS. Treatment of advanced Parkinson’s disease. Curr Opin Neurol 2014; 27:450–460. 3. Robottom BJ, Weiner WJ, Factor SA. Movement disorders emergencies. Part 1: hypokinetic disorders. Arch Neurol 2011; 68:567–572. 4. Taguchi S, Niwa J, Ibi T, Doyu M. Dyskinesia-hyperpyrexia syndrome in a & patient with Parkinson’s disease: a case report. Rinsho Shinkeigaku 2015; 55:182–184. This article describes DHS after switch from immediate to extended release dopamine agonist without changing the levodopa equivalent dose. 5. Frucht SJ. Treatment of movement disorder emergencies. Neurotherapeutics & 2014; 11:208–212. This is an updated and concise review article focused on the treatment of movement disorders emergencies. 6. Sa´ DS, Teive HA, Troiano AR, Werneck LC. Parkinsonism associated with neurocysticercosis. Parkinsonism Relat Disord 2005; 11:69–72. 7. Munhoz RP, Teive HA, Troiano AR, et al. Parkinson’s disease and thyroid dysfunction. Parkinsonism Relat Disord 2004; 10:381–383. 8. Tousi B. Movement disorder emergencies in the elderly: recognizing and treating an often-iatrogenic problem. Cleve Clin J Med 2008; 75:449–457. 9. Munhoz RP, Teive HA, Eleftherohorinou H, et al. Demographic and motor features associated with the occurrence of neuropsychiatric and sleep complications of Parkinson’s disease. J Neurol Neurosurg Psychiatry 2013; 84:883–887. 10. Moscovich M, No´vak FT, Fernandes AF, et al. Neuroleptic malignant syndrome. Arq Neuropsiquiatr 2011; 69:751–755. 11. Belvederi Murri M, Guaglianone A, Bugliani M, et al. Second-generation && antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis. Drugs R D 2015; 15:45–62. This review highlights the potential for NMS related to both classic and newer antipsychotics.
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12. Dosi R, Ambaliya A, Joshi H, Patell R. Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary. BMJ Case Rep 2014; 23:2014. This review is focused on NMS and serotonergic syndrome, including differential diagnosis and detection of often missed diagnoses clues. 13. Burkhard PR. Acute and subacute drug-induced movement disorders. Parkinsonism Relat Disord 2014; 20 (Suppl 1):S108–S112. 14. Langan J, Martin D, Shajahan P, Smith DJ. Antipsychotic dose escalation as a trigger for neuroleptic malignant syndrome (NMS): literature review and case series report. BMC Psychiatry 2012; 12:214. 15. Berardi D, Dell’Atti M, Amore M, et al. Clinical risk factors for neuroleptic malignant syndrome. Hum Psychopharmacol 2002; 17:99–102. 16. Levinson DF, Simpson G. Sequelae of neuroleptic malignant syndrome. Biol Psychiatry 1987; 22:273–278. 17. Buggenhout S, Vandenberghe J, Sienaert P. Electroconvulsion therapy for neuroleptic malignant syndrome. Tijdschr Psychiatr 2014; 56:612–615. 18. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005; 352:1112–1120. 19. Munhoz RP. Serotonin syndrome Induced by a combination of bupropion and SSRIs. Clin Neuropharmacol 2004; 27:219–222. 20. Lane R, Baldwin D. Selective serotonin reuptake inhibitor-induced serotonin syndrome: review. J Clin Psychopharmacol 1997; 17:208–221. 21. Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician 2010; 81:1139–1142. 22. Dunkley EJ, Isbister GK, Sibbritt D, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003; 96:635–642. 23. Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med 1998; 16:615–619. 24. Pinyavat T, Rosenberg H, Lang BH, et al. Accuracy of malignant hyperthermia diagnoses in hospital discharge records. Anesthesiology 2015; 122:55–63. 25. Schuster F, Moegele S, Johannsen S, Roewer N. Malignant hyperthermia in & the intensive care setting. Crit Care 2014; 18:411. This report highlights the need to consider malignant hyperthermia outside operating room settings. 26. Mathews KD, Moore SA. Multiminicore myopathy, central core disease, malignant hyperthermia susceptibility, and RYR1 mutations: one disease with many faces? Arch Neurol 2004; 61:27–29. 27. Cardoso F. Chorea: nongenetic causes. Curr Opin Neurol 2004; 17:433–436. 28. Cardoso F. Movement disorders in childhood. Parkinsonism Relat Disord 2014; 20 (Suppl 1):S13–S16. 29. Miyasaki JM, Aldakheel A. Movement disorders in pregnancy. Continuum (Minneap Minn) 2014; 20:148–161. 30. Robottom B, Factor SA, Weiner WJ. Movement disorders emergencies part 2. Arch Neurol 2011; 68:719–724. 31. Dewey RB, Jankovic J. Hemiballism-hemichorea. Clinical and pharmacologic findings in 21 patients. Arch Neurol 1989; 46:862–867. 32. Postuma RB, Lang AE. Hemiballism: revisiting a classic disorder. Lancet Neurol 2003; 2:661–668. 33. Mestre TA, Ferreira JJ, Pimentel J. Putaminal petechial haemorrhage as the cause of nonketotic hyperglycaemic chorea: a neuropathological case correlated with MRI findings. J Neurol Neurosurg Psychiatry 2007; 78:549–550. 34. Teive HA, Munhoz RP, Souza MM, et al. Status dystonicus: study of five cases. Arq Neuropsiquiatr 2005; 63:26–29. 35. Fasano A, Ricciardi L, Bentivoglio AR, et al. Status dystonicus: predictors of outcome and progression patterns of underlying disease. Mov Disord 2012; 27:783–788. 36. Sandroni C, Cariou A, Cavallaro F, et al. Prognostication in comatose & survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine. Intensive Care Med 2014; 40:1816–1831. This review shows the evidence on predictors of poor outcome in comatose patients after cardiac arrest, highlighting the prognostic role of MSE. 37. Ferlazzo E, Gasparini S, Cianci V, et al. Serial MRI findings in brain anoxia leading to Lance-Adams syndrome: a case report. Neurol Sci 2013; 34:2047–2050. 38. Cheung MC, Shahed J, Jankovic J. Malignant Tourette syndrome. Mov Disord 2007; 22:1743–1750.
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Movement disorders emergencies Renato P. Munhoz a, Laura M. Scorr b, and Stewart A. Factor b
Purpose of review Although movement disorders are traditionally viewed as chronic diseases that are followed electively, a growing number of these patients present with acute, severe syndromes or complications of their underlying neurological problem. Identifying and managing movement disorders emergencies is challenging, even for the specialist. This review summarizes evidence outlining the clinical presentation of acute, life-threatening movement disorders. Recent findings We review the most significant aspects in the most common movement disorders emergencies, including acute complications related to Parkinson’s disease and parkinsonism, serotonergic, and neuroleptic malignant syndromes, chorea, ballismus, dystonia, myoclonus, and tics. Summary The increasing amount of information delineating the descriptions of movement disorders emergencies provides means for more effective prevention, identification, and management for the nonspecialist. Although the commonest of these syndromes eventually have a good outcome, serious conditions such as neuroleptic malignant syndrome and status dystonicus may induce substantial rates of morbidity and mortality. This review re-emphasizes the need for their prompt identification and management. Keywords movement disorders emergencies, neuroleptic malignant syndrome, serotonergic syndrome, status dystonicus
INTRODUCTION Movement disorders encompass disabling syndromes typically viewed as a realm of inexorably progressive chronic disorders that are, in most cases, followed and treated in ambulatory care settings. More recently, this view has been challenged by the growing body of literature as well as clinical experience showing that movement disorders can also present acute and more aggressively [1]. The concept of movement disorders emergencies has been coined to address such situations, as a neurological disorder evolving acute or subacutely, in which the clinical presentation is dominated by movement disorders and in which failure to accurately diagnose and manage the patient may result in significant morbidity or even mortality. Here, we used these criteria to concisely review diagnostic approaches to movement disorders emergencies by identifying the phenomenology according to the predominant abnormal movement pattern, describing common causes and therapeutics.
EMERGENCIES IN PARKINSON’S DISEASE Severe motor fluctuations Motor fluctuations in Parkinson’s disease typically are not severe enough to need urgent interventions; www.co-neurology.com
however, some patients may present extremely disturbing and dramatic ‘off’ periods, especially when they occur suddenly, associated with prominent akinesia, dysautonomia, and psychiatric features, such as anxiety and panic. In these instances, history should look for potential triggers or aggravating factors, including infections, dopaminergic medication changes, and inclusion of antidopaminergic drugs. Management involves combined approaches: fragmentation of daily doses of levodopa, crushed tablets, controlled-release or dispersible levodopa, subcutaneous dopamine agonists, monoamine oxidase B (MAO-B) and catechol-Omethyltransferase (COMT) inhibitors, and elective stereotactic surgery [2].
a Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada and bDepartment of Neurology, Emory University School of Medicine, Emory University, Atlanta, Georgia, USA
Correspondence to Renato P. Munhoz, Movement Disorders Centre, Toronto Western Hospital, 399 Bathurst Street, McL7-419, Toronto, ON M5T 2S8, Canada. Tel: +1 416 603 5800 x5214; fax: +1 416 603 5004; e-mail: [email protected] Curr Opin Neurol 2015, 28:406–412 DOI:10.1097/WCO.0000000000000212 Volume 28 Number 4 August 2015
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Movement disorders emergencies Munhoz et al.
Acute parkinsonism/acute worsening of parkinsonism
KEY POINTS Neuroleptic malignant syndrome, serotonergic syndrome, and malignant hyperthermia are lifethreatening emergencies with sometimes subtle clinical presentations that can be distinguished based on history of drug exposure. In Parkinson’s disease, acute psychosis or worsening of the motor features are usually associated with or triggered by concurrent medical conditions such as infections, metabolic disturbances, or neurological disorders. Acute parkinsonism has a relatively broad differential diagnosis; however, most cases are drug induced, often related to high potency DRBs in parenteral formulations. Status dystonicus is a potentially fatal and unusual complication of dystonia that often requires prompt, complex, and aggressive interventions, although no formally established management guidelines exist.
Acute severe de-novo parkinsonism is uncommon, most frequently caused by exposure to potent dopamine receptor blockers (DRBs), such as neuroleptics and antiemetics. Other rare causes include hypoxic– ischemic encephalopathy, intoxications, acute hydrocephalus, and infections [3,5 ,6]. Table 1 lists the broader differential diagnosis. Acute worsening of motor symptoms in Parkinson’s disease, unrelated to disease progression, typically occurs because of concurrent medical conditions, such as urinary or respiratory tract infections, metabolic disturbances, or neurological disorders (subdural hematoma, spinal cord lesion, brain tumor, etc.) [1,3,7]. &
Table 1. Differential diagnosis for acute parkinsonism Cause Drug induced Neuroleptics Antiemetics
Parkinsonism–hyperpyrexia and dyskinesia– hyperpyrexia syndromes Parkinsonism–hyperpyrexia syndrome (PHS) mimics neuroleptic malignant syndrome (NMS) in patients with Parkinson’s disease [3]. It is characterized by hyperthermia, dysautonomia, altered consciousness, severe rigidity, and elevated serum creatine kinase levels. PHS may be triggered by infections, hot weather, dehydration, and, particularly, reduction or withdrawal of antiparkinsonian agents (levodopa, dopamine agonists, and amantadine). Commonest situations in which PHS occurs in the context of dopaminergic treatment discontinuation include noncompliance, hospital admission due to comorbidities, or as part of the preoperative procedure for stereotactic surgery. Interestingly, recurrent PHS was described after discontinuation of subthalamic nucleus deep brain stimulation. Potentially fatal complications include venous thrombosis, pulmonary embolism, aspiration pneumonia, and renal failure. Treatment is based on supportive measures and reinstitution of adequate dopaminergic therapy. Occasionally, dantrolene is necessary [3]. Dyskinesia–hyperpyrexia syndrome (DHS) consists of severe dyskinesias leading to muscle exhaustion, rhabdomyolysis, hyperthermia, and confusion. It shares some of the features of PHS; however, dyskinesias – not rigidity – predominate. In addition, DHS, contrarily to PHS, should be treated by cautiously reducing the dosage of dopaminergic drugs [4 ]. &
Anticonvulsants Cytotoxic agents Antidepressants Intoxications Carbon monoxide Methanol Organophosphates 1-Methyl-1–4-phenyl-4-proprionoxypiperidine (MPTP) Manganese Cyanide Disulfiram Structural Subdural hematoma Hydrocephalus Strategic ischemic lesions Tumors Infections/postinfectious/inflammatory Viral encephalitis HIV Postinfectious Autoimmune Metabolic Pontine and extrapontine myelinolisis Diabetic uremia Hepatic encephalopathy Genetic Rapid-onset dystonia parkinsonism Acute decompensation in Wilson’s disease Functional
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For both acute situations, treatment should be focused on resolution of underlying etiologic processes. Occasionally, symptomatic treatment with dopaminergic agents is required [8].
Acute psychosis in Parkinson’s disease Psychosis occurs in up to half of cases with Parkinson’s disease throughout the disease course, frequently associated and triggered by the same agents used to treat the motor symptoms; however, acute clinical conditions (infectious, metabolic, or neurological disorders) may play a role [8,9]. Manifestations include visual hallucinations, delusions, confusion, and agitation. After treatment of potential comorbidities, a stepwise withdrawal of potentially contributing agents is recommended, starting with anticholinergics, followed by MAO-B inhibitors, dopamine agonists, amantadine, and COMT inhibitors. Introduction of an antipsychotic (clozapine or quetiapine) may be necessary [3,5 ,8]. &
Neuroleptic malignant syndrome NMS is an idiosyncratic abrupt reaction to DRB [10]. Often, agents include ‘classic’ neuroleptics; however, newer ‘atypical’ agents have all also been implicated, the safest being clozapine and quetiapine [11 ]. In addition, NMS can occur with other &&
dopamine-blocking drugs or as PHS, after abrupt withdrawal of dopaminergic agents [1,3,12 ,13]. Usually, symptoms start during the first 2 weeks of treatment initiation or dosage change [14]. Risk factors include abrupt dose escalation, depot formulations, male sex, young age, use of lithium and selective serotonin reuptake inhibitors (SSRIs), high temperatures, dehydration, exhaustion, extrapyramidal syndromes, and previous NMS episode (Table 2) [15]. All age groups can be affected, most cases are in their fourth and fifth decades [10,12 ,15]. Mortality remains high between 20 and 30% of cases [1,3]. Most survivors recover without sequelae; however, some present cognitive and motor abnormalities, including rigidity, tremor, and dystonia [16]. Diagnostic criteria combine the tetrad of hyperthermia, rigidity, altered mental status, and dysautonomia. Associated signs include tremor, dystonia, chorea, myoclonus, seizures, ataxia, hyporeflexia, and extensor plantars [3,10,12 ]. In addition, laboratory changes include raised serum creatine kinase (>1000 IU/l), impaired liver, renal, and coagulation status tests, leukocytosis, electrolyte disturbances, proteinuria, rhabdomyolysis, and myoglobinuria [1,10,12 ]. The most important differential diagnoses are serotonergic syndrome, malignant hyperthermia, and catatonia [1,12 ,13]. Treatment depends on recognition, exclusion of differential diagnoses, medication withdrawal, &&
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Table 2. Comparison of features and management of neuroleptic malignant syndrome, serotonergic syndrome, and malignant hyperthermia Neuroleptic malignant syndrome
Serotonergic syndrome
Malignant hyperthermia
Age/sex prodisposition
Young men
None
Children, young adults
Triggering factor
Idiosyncratic
Drug combination/ overdose
Gene mutation
Onset
Acute
Subacute
Acute
Causative agents
Classic/newer antipsychotics, antiemetics, L-dopa withdrawal
SSRIs, SNRIs, tricyclic antidepressants, MAOIs, L-tryptophan, amphetamines, cocaine
Volatile anesthetics, succinylcholine
Fever
þþþ
þþ
þþþ
Confusion
þþþ
þþþ
þ
Dysautonomia
þþþ
þþþ
þþþ
Motor features
Tremor, rigidity
Myoclonus, rigidity, stereotypies, hyperreflexia
Rigidity
Diaphoresis
þþþ
þþ
þþþ
Elevated serum creatine kinase
þþþ
þþ
þþþ
Elevated serum transaminases
þþþ
þ
Metabolic acidosis
þ
þ
þþ
Pharmacologic treatmenta
Bromocriptine, amantadine, dantrolene
Cyproheptadine, methylsergide
Dantrolene
MAOIs, monoamine oxidase inhibitors; NMS, neuroleptic malignant syndrome; SNRIs, serotonin–norepinephrine inhibitors; SSRIs, selective serotonin reuptake inhibitors. a Prior to any form of pharmacological treatment, patients should be stabilized and withdrawn of causative agent.
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Movement disorders emergencies Munhoz et al. Table 3. Differential diagnosis of acute chorea and ballismus Vascular
Ischemic/hemorrhagic stroke Malformations Postpump chorea Polycythemia vera Nonketotic hyperglycemia Hypoglycemia Uremic encephalopathy Hyperthyroidism Hypoparathyroidism
Structural
Basal ganglia lesion or mass Cerebellar lesion or mass Thalamotomy or subthalomotomy
Infectious
Cryptococcal granuloma Toxoplasmosis Tuberculoma HIV encephalitis
Autoimmune
Postinfectious/Sydenham chorea/ chorea gravidarum Systemic lupus erythematosus Antiphospholipid antibody syndrome Scleroderma Behcet disease Polyarteritis nodosa Sarcoidosis Multiple sclerosis Paraneoplastic (CV2/CRMP-5 antibodies)
Iatrogenic
Serotonergic syndrome results most often from the combination of two or more agents that enhance serotonergic activity or concentration in the central nervous system [1,3,12 ,18]. This underrecognized syndrome presents with agitation, mental status changes, myoclonus, ataxia, postural instability, hyperreflexia, rigidity, and dysautonomia after changes in serotonergic drug regimen [1,19]. Onset is typically abrupt but some patients report insidious or recurrent subtle cognitive decline, behavioral abnormalities, and tremor with postural changes days to weeks before the full-blown syndrome develops [18]. Serotonergic syndrome is a predictable reaction. The offending drugs are those that cause excessive brainstem and spinal cord serotonin or 5-hydroxytryptamine (5-HT) type 1A receptor stimulation [18,20]. The most common implicated agents are listed in Table 2, but although any of them can potentially cause serotonergic syndrome, a combination is usually needed, with greater risk for monoamine oxidase inhibitors or SSRIs concomitantly used with any other serotonergic agent [18]. Although doses taken are commonly within therapeutic limits, 20% of cases occur secondary to overdose [1,21]. Other risky circumstances include rapid titration, addition or switch to a new agent without proper washout period, liver or renal disease, endogenously reduced monoamine oxidase A activity, cytochrome P4502D6 enzyme inhibition, and old age [19]. Serum or cerebrospinal fluid serotonin levels are useless for diagnosis, which is established on clinical grounds [12 ,18]. The starting point is obviously the history of medication exposure, added by clinical manifestations. The most widely used diagnostic criteria require the positive medication history along with any of the following: myoclonus, agitation or diaphoresis; unexplained hyperthermia; hypertonia; and tremor and hyperreflexia, after other causes have been ruled out [22]. Seizures, renal failure, and coagulopathy may occur [1,3,18,20]. Laboratory abnormalities include metabolic acidosis, rhabdomyolysis, elevated white cell count, and serum aminotransferase and creatinine levels. Differential diagnoses include cocaine or lithium overdose, anticholinergic poisoning, malignant hyperthermia, and NMS, each readily distinguished from serotonergic syndrome based on medication exposure history [12 ,19,22]. Treatment requires medication withdrawal, enough to improve half of all cases [1,3]. Persistent/severe symptoms require pharmacologic treatment. Nonspecific 5-HT receptor blockers (cyproheptadine and methysergide) have been &&
Cerebral anoxia
Metabolic
Serotonergic syndrome
Anticonvulsants Oral contraceptives Levodopa
&&
Cocaine Amphetamines Morphine Methadone Alcohol
supportive care, and pharmacological interventions depending on severity and presence of complications [1,3,10]. Severe symptoms require intensive care management and pharmacological reduction of rigidity (benzodiazepines or dantrolene) and dopaminergic blockage (bromocriptine or levodopa), as well as control of agitation [10,12 ,13]. Electroconvulsive therapy has been used anecdotally [17]. Neuroleptics should be stopped for at least 2 weeks after the acute phase. Management of the underlying psychiatric condition can be then restarted with low doses, slow titration, avoiding lithium, and with close observation to prevent recurrence [1,10]. &&
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Movement disorders Table 4. Pharmacological treatment of movement disorders Movement disorder
Medication class
Medication
Initial – maximum daily dose (mg)
Chorea
Neuroleptic
Haloperidol
0.5–8
Risperidone Dopamine-depleting agent
Ballism Myoclonus
Tics
0.5–6
Tetrabenazine
12.5–75
Benzodiazepine
Clonazepam
0.5–6
Anticonvulsant
Valproic acid
750–1500 12.5–200
Dopamine-depleting agent
Tetrabenazine
Neuroleptic
Haloperidol
Anticonvulsant
Levetiracetam
500–3000
Valproic acid
750–1500
Benzodiazepine
Clonazepam
0.5–6
Neuroleptic
Pimozide
1–10
Haloperidol
0.5–8
Risperidone
0.5–6
Dopamine-depleting agent Antihypertensives
0.5–8
Tetrabenazine
12.5–75
Clonidine
0.1–0.6
Guanfacine Dystonic storm
Anticholinergic
1–3
Trihexyphenidyl
5–20
Diphenhydramine Dopamine blocker
25–400
Haloperidol
0.5–8
Pimozide Acute dystonic reaction
1–10
Dopamine-depleting agent
Tetrabenazine
12.5–75
Anticholinergic
Benzotropine
1–6
Diphenhydramine
credited with shortening the syndrome’s duration [1,23]. Other agents include benzodiazepines, chlorpromazine, and propranolol. Treatment of seizures, arrhythmias, coagulopathy, rigidity, and hyperthermia may be necessary [23]. Serotonergic syndrome is potentially fatal, mortality rates range from 2.4 to 12% [20,21]. As in NMS, reintroduction of treatment of the underlying psychiatric disorder requires close monitoring, low dose, and slow titration [19,21].
Malignant hyperthermia Malignant hyperthermia is a rare genetic muscle disorder that occurs when a mutation-positive patient is exposed to inhalation anesthetics or depolarizing muscle relaxants [24]. Malignant hyperthermia manifests with abrupt hyperthermia, fluctuations in blood pressure, hypercarbia, hyperkalemia, metabolic acidosis, rigidity, and rhabdomyolysis [25 ]. Malignant hyperthermia results from uncontrolled calcium flux across muscle membrane, in more than half of cases due to a dominant mutation on the gene encoding skeletal muscle type-1 ryanodine receptor [26]. Dantrolene can be effective &
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25–400
treatment, along with correction of metabolic and electrolyte abnormalities. At present, with appropriate management and awareness, mortality is less than 5% [24,25 ]. Comparison of NMS, serotonergic syndrome, and malignant hyperthermia is shown in Table 2. &
Chorea and ballismus Acute severe chorea can result from numerous causes including drug exposures, toxic/metabolic derangements, vascular disease, infectious/postinfectious, and autoimmune disorders, leading to hyperthermia and rhabdomyolysis if not recognized and treated aggressively. Sydenham chorea is a childhood-onset manifestation of rheumatic fever [27]. Additional features include behavioral changes, weakness, hypotonia, and vocalizations. The diagnosis is clinical with supportive laboratory tests often showing elevated a-streptolysin-O and a-DNAase-B titers [28]. The most widely used symptomatic treatment of chorea under these circumstances is valproic acid at doses of 10–25 mg/kg/day. DRB should be reserved for severe and refractory cases because of the associated Volume 28 Number 4 August 2015
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Movement disorders emergencies Munhoz et al.
risk of complications [27,28]. Chorea gravidarum has been historically associated with a past history of rheumatic fever or Sydenham chorea, but chorea arising during pregnancy can also be drug induced or associated with systemic lupus erythematosus, antiphospholipid antibody syndrome, syphilis, and encephalitis [29]. In the case of classic chorea gravidarum, chorea typically begins in the first trimester. One-third of cases resolve spontaneously before delivery, and the remainder within hours after delivery. When necessary, after the first trimester, low-dose haloperidol has been shown to be effective [27,29]. Ballism defines larger amplitude, coarse, forceful movements often occurring acute and unilaterally. Ballism and chorea may in fact represent a continuum of hyperkinetic movements differentiated by speed and amplitude [30]. The most common cause of hemiballism is vascular, classically taught to indicate a lesion to the contralateral subthalamic nucleus. However, this topography is uncommon and lesions in multiple areas have been implicated [31,32]. Nonketotic hyperglycemia can result in unilateral or bilateral ballism, typically in elderly females, as a presenting feature of diabetes mellitus or in established cases [32,33]. Brain MRI T1weighted images typically show high signal in the contralateral putamen and occasionally in the globus pallidus, findings thought to result from petechial hemorrhages [33]. Abnormal movements tend to subside when the metabolic disturbance normalizes, but may be permanent. Other causes of acute ballism and chorea are listed in Table 3. Most cases resolve spontaneously within months. Table 4 shows treatment options when required. Treatment-refractory patients may need stereotactic surgery [5 ]. &
Dystonia Patients with inherited, acquired, or idiopathic dystonia can develop acute worsening with severe, continuous contractures, a phenomenon referred to as ‘dystonic storm’ or status dystonicus. Several factors can precipitate status dystonicus including infection, medication changes, and trauma [34,35]. As the sustained contractures can be life threatening, ICU admission is necessary, in addition to a stepwise pharmacological approach that includes anticholinergics, DRB, dopamine depletors, sedation, and paralyzing agents. In refractory status dystonicus, stereotactic surgery has been tried [35]. Acute dystonic reactions can be seen after exposure to DRB, typically within 24 h of exposure. Risk is increased in men and when the dose is rapidly titrated [1,30]. Manifestations can combine
blepharospasm, cervical, laryngeal or limbs dystonia, and oculogyric crisis. Life-threatening respiratory compromise can occur when the larynx or pharynx are affected. Management includes parenteral anticholinergics or antihistamines, after the precipitating agent is discontinued [1].
Myoclonus Myoclonus can present emergently, especially in the inpatient setting, and be a harbinger of an underlying toxic metabolic derangement, drugs reaction (as in serotonergic syndrome and NMS), or cerebral hypoxia. Two myoclonic syndromes can result from cerebral anoxia: myoclonus status epilepticus (MSE) and Lance Adams syndrome (LAS) [36 ,37]. MSE usually indicates poor prognosis and begins within hours of the anoxic event with spontaneous, unrelenting, generalized, or multifocal myoclonus in comatose patients [36 ]. LAS or postanoxic myoclonus has a delayed onset, with stimulus sensitive and action-induced movements [37]. LAS may improve spontaneously over years or be unrelenting. When myoclonus is particularly disabling, treatment may include clonazepam, valproic acid, and levetiracetam (Table 4) [30]. Finally, myoclonus may be a drug reaction induced by the same agents that cause serotonergic syndrome and NMS, added by opiates, gabapentin, antibiotics, and spinal anesthetics. &
&
Tics Although the majority of patients with tic disorders have a benign course, neurologic injury due to intense exacerbation may be an uncommon emergency, including cases in which head thrusting with violent neck movements resulted in compressive neuropathies, myelopathies, and subdural hematoma [38]. Factors known to markedly worsen tics include fatigue, stress, infection, and medications (stimulants, tricyclic antidepressants, and SSRIs). After the precipitating factor has been removed, pharmacologic treatment may be necessary using neuroleptics and dopamine depleting agents [30].
CONCLUSION The scope of the movement disorders provided in this review was intended to focus on life-threatening syndromes that diverge from the archetypal potentially severe but chronic, insidious disorders seen on most specialized ambulatory care clinics. Some of them have uncertain diagnostic criteria and are managed using an assemblage of anecdotal treatment options. These disorders may, therefore,
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present as sources diagnostic confusion and treatment dilemmas in emergency settings. Future directions should be directed not only to advance the basic and clinical aspects of these disorders but also to disseminate means for more accurate and prompt diagnosis and interventions. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Munhoz RP, Moscovich M, Araujo PD, Teive HA. Movement disorders emergencies: a review. Arq Neuropsiquiatr 2012; 70:453–461. 2. Giugni JC, Okun MS. Treatment of advanced Parkinson’s disease. Curr Opin Neurol 2014; 27:450–460. 3. Robottom BJ, Weiner WJ, Factor SA. Movement disorders emergencies. Part 1: hypokinetic disorders. Arch Neurol 2011; 68:567–572. 4. Taguchi S, Niwa J, Ibi T, Doyu M. Dyskinesia-hyperpyrexia syndrome in a & patient with Parkinson’s disease: a case report. Rinsho Shinkeigaku 2015; 55:182–184. This article describes DHS after switch from immediate to extended release dopamine agonist without changing the levodopa equivalent dose. 5. Frucht SJ. Treatment of movement disorder emergencies. Neurotherapeutics & 2014; 11:208–212. This is an updated and concise review article focused on the treatment of movement disorders emergencies. 6. Sa´ DS, Teive HA, Troiano AR, Werneck LC. Parkinsonism associated with neurocysticercosis. Parkinsonism Relat Disord 2005; 11:69–72. 7. Munhoz RP, Teive HA, Troiano AR, et al. Parkinson’s disease and thyroid dysfunction. Parkinsonism Relat Disord 2004; 10:381–383. 8. Tousi B. Movement disorder emergencies in the elderly: recognizing and treating an often-iatrogenic problem. Cleve Clin J Med 2008; 75:449–457. 9. Munhoz RP, Teive HA, Eleftherohorinou H, et al. Demographic and motor features associated with the occurrence of neuropsychiatric and sleep complications of Parkinson’s disease. J Neurol Neurosurg Psychiatry 2013; 84:883–887. 10. Moscovich M, No´vak FT, Fernandes AF, et al. Neuroleptic malignant syndrome. Arq Neuropsiquiatr 2011; 69:751–755. 11. Belvederi Murri M, Guaglianone A, Bugliani M, et al. Second-generation && antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis. Drugs R D 2015; 15:45–62. This review highlights the potential for NMS related to both classic and newer antipsychotics.
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