Movement Disorders Emergencies MASHARIP ATADZHANOV, MD, PhD, DSc, FRCP Professor of School of Medicine, University of Zambia. June 27, 2021 Lecture Overview • Learning objectives • Definition • Classification • Clinical Presentation • The principles of management Learning Objectives • Recognize the clinical presentation and key management aspects of common movement disorders emergencies.

• Formulate an organized approach to the evaluation and diagnosis movement disorders emergencies.

• Define the role of advanced practice providers in the care of adult patients with movement disorders emergencies in an emergency room setting. Definition

• A emergency has been defined as an event where patients develop a movement disorder over hours or several days, and in which morbidity and even mortality can result from failure to appropriately diagnose and manage the patient (Poston and Frucht 2008). Classification • There is no generally accepted classification of movement disorders emergencies. • Robottom, Weiner, and Factor (2011), divide them into Hypokinetic and Hyperkinetic disorders. 1. Hypokinetic disorders include: a) The drug-induced movement disorder emergencies:  Neuroleptic malignant syndrome  -hyperpyrexia syndrome  Classification b) Emergency complications related to the management of Parkinson disease (PD):  Motor Fluctuations and  Psychosis in PD  Acute parkinsonism

2. Hyperkinetic disorders include:   Ballism   Tics  : , Acute Dystonic Reaction, Acute Torticollus Classification Renato P. Munhoz, et al. (2012) divide MD emergencies into six main topics: 1. Emergencies in Parkinson's disease (PD). 2. Acute drug reactions. 3. Acute exacerbation of chronic MDs. 4. Acute chorea and hemiballism-hemichorea 5. Stiff-person syndrome 6. Lethal catatonia Hypokinetic Movement Disorder Emergencies Neuroleptic malignant syndrome (NMS) • NMS is one of the cardinal movement disorder emergencies.

• There are no definitive lab tests and imaging, the diagnosis is commonly based on clinical presentation.

• The incidence of NMS is low and a high index of suspicion is critical to making the diagnosis of NMS, and the disorder should be considered in any patient with acute-onset parkinsonism and fever.

• Most cases of MNS are caused by antipsychotics (Risperidon, clozapine, chlorpromazine, etc), and other medications such as prochlorperazine, metoclopramide, droperidol, promethazine, and even agonists (DA). Hypokinetic Movement Disorder Emergencies • Pathogenesis of NMS is not clear. “Central” dopaminergic hypofunction and “peripheral” sympathoadrenergic hyperactivity suggested.

• Onset - Symptoms often begin after initiation or an increase in neuroleptic dose. The syndrome increases in severity over 48 to 72 hours and lasts 7 to 14 days.

• NMS usually develops over days. But sometimes its onset may be fulminant, progressing to coma over hours. Hypokinetic Movement Disorder Emergencies Clinical Presentation • Most patients have fever, rigidity, mental status change (agitation, delirium), autonomic dysfunction, and other movement disorders (, dystonia, and myoclonus).

• Rigidity may be so severe that the limbs cannot be moved, and the stiffness may be fairly fixed. In some, muscle contractions may mimic a tonic .

• Many patients have extreme elevations of creatine phosphokinase (CPK)(>1000IU/L) due to rhabdomyolysis, but this is not required for the diagnosis. Elevations in the CPK to the 1,000–2,000 range are sometimes seen in otherwise normal, treated psychotic patients, even in the absence of signs or symptoms of muscle or tone abnormalities. Hypokinetic Movement Disorder Emergencies • Dif diagnosis. Delirium, malignant catatonia, serotonin syndrome, etc.

• Management. Key steps in treatment: Excluding infection, identifying and discontinuing the causative agent, close monitoring of autonomic and respiratory parameters, and treatment with dopaminergic replacement (either levodopa or dopamine agonists).

• Combination therapy safe and effective, and treatment should continue for 7 to 10 days depending on the half-life of the causative agent. F.e. Lorazepam 1-2mg im or iv qid; Bromocriptin 2.5-5mg p o tid, Amantadine 100mg po tid, Dantrolene 1-2.5mg/kg iv qid for 48h Hypokinetic Movement Disorder Emergencies Parkinsonism-hyperpyrexia syndrome (PHS) • Parkinsonism-hyperpyrexia syndrome (PHS) occurs in patients with PD who abruptly withdraw or reduce dopaminergic medications.

• PHS also known as neuroleptic malignant-like syndrome, characterized by hyperthermia, autonomic dysfunction, altered consciousness, severe rigidity and elevated serum creatine kinase (CK) levels. Hypokinetic Movement Disorder Emergencies • PHS may be triggered by infections, reduction in dopaminergic drug dosage, hot weather or dehydration. Potentially life-threatening complications include deep venous thrombosis and pulmonary embolism, aspiration pneumonia and renal failure.

• Treatment is based on intravenous fluids infusion, antithermics and use of levodopa and dopamine agonists . Occasionally, dantrolene may be necessary. Hypokinetic Movement Disorder Emergencies Dyskinesia-hyperpyrexia syndrome (DHS) • Levodopa-induced can be severe and occasionally even life- threatening, presenting as a dyskinetic storm (also known as dyskinesia- hyperpyrexia syndrome).

• Clinical picture - Patients typically present with prolonged episodes of generalized and exhausting dyskinetic movements that eventually cause motor collapse with consequent dehydration and rhabdomyolysis.

• Reducing the dosage of dopaminergic drugs almost always improves dyskinesias in a short period of time.

• Patients may also need rehydration, electrolyte monitoring, sedation with . may be a feasible long-term treatment. Hypokinetic Movement Disorder Emergencies Malignant catatonia • MC is a nonspecific syndromic subtype of catatonia associated with many toxic- metabolic and neuropsychiatric illnesses. Traditionally catatonia has been classified as “retarded,” “excited,” and “malignant”. • MC has similar clinical features to NMS, it is difficult to distinguish these diseases in patients. • The pathogenesis of MC is unclear. Dysfunction in the GABA, glutamate and dopaminergic systems play important role in the pathogenesis of MC. • There are no gold standard diagnostic tests, clinical features are most important for the diagnosis. • Benzodiazepines have become the mainstay of first-line treatment with remission rates as high as 70–80%. Supportive care and targeting the underlying process. Some patients need ECT. Hypokinetic Movement Disorder Emergencies Serotonin Syndrome (SS) • SS is a potentially life-threatening disorder that results most often from the combined use of two or more agents that enhance serotonin (ST) activity or concentration in the CNS.

• Inhibition of serotonin reuptake, inhibition of presynaptic release, and monoamine oxidase inhibition are postulated mechanisms of SS.

• Diagnosis is established on clinical grounds.

• Clinical manifestations falling in a spectrum ranging from restlessness and to life-threatening toxicity, associated with ST levels. Hypokinetic Movement Disorder Emergencies • Cl manifestations: altered mental status, autonomic instability and motor abnormalities, including tremor, myoclonus, gait and appendicular , and muscle rigidity…

• The most widely used and validated diagnostic criterion is the Hunter Serotonin Toxicity Criteria that includes the use of a serotonergic agent plus any of the following: (i) myoclonus, agitation or diaphoresis; (ii) tremor and hyperreflexia; (iii) hypertonia; (iv) temperature above 38 degrees Celsius.

• Management. Symptoms can start as early as 6 hours after initiating the offending agent. i) Discontinue offending agents ii)Supportive care Vitals, oxygenation, hydration, cardiac monitoring iii) ST antagonist Cyproheptadine iv) Benzodiazepines. Hypokinetic Movement Disorder Emergencies Acute Parkinsonism. • People with Parkinson’s disease may develop acute and subacute complications that are serious or even life-threatening, and require urgent medical attention.

• Secondary parkinsonism, defined by having an identifiable non- neurodegenerative disorder which evolves over weeks or even hours.

• The major causes of acute parkinsonism are Infectious, post- infectious, autoimmune, paraneoplastic, medications, toxins (carbon monoxide, MPTP), structural brain lesions (, pontine myelinolysis, etc), neuropsychiatric (catatonia, conversion disorder). Hypokinetic Movement Disorder Emergencies • Clinical Presentation depends on the causes of acute parkinsonism.

• Management - Establishing the etiology of acute parkinsonism is of paramount importance.

• A trial of levodopa to target akinesia and rigidity is recommended in all cases due to minimal associated side effects. Postsynaptic therapies (dopamine agonists) can also be considered. Hyperkinetic Movement Disorder Emergencies Chorea • Chorea is a hyperkinetic movement disorder characterized by continuous, nonrhythmic, nonpatterned involuntary movements.

• The distinction between chorea, , ballismus is somewhat arbitrary and relates more to speed, amplitude, and duration of the movement rather than underlying pathology.

• Chorea may present acutely in several settings, Causes of chorea include: drug or toxin exposure, infectious, autoimmune conditions, metabolic(hyper/hypoglycemia, hyper/hyponatremia, etc),and others.

• Most common causes of chorea in children is Sydenham chorea due to rheumatic fever. Sydenham disease cover the entire spectrum of its clinical features Hyperkinetic Movement Disorder Emergencies • Acute chorea-ballism - stroke is the most common cause of acute chorea-ballism in adults. Acute chorea-ballism classically occurs in nonketotic and ketotic hyperglycemia. classically begin in the first trimester of pregnancy, one- third of cases resolve spontaneously prior to delivery. Chorea may emerge or reemerge during use of oral contraceptive pills.

• Treatment - Identification of the cause of chorea. Symptomatic therapy with dopamine receptor blocking agents. A combination of a benzodiazepine with either haloperidol or , deutetra- benazine. Other options include gabapentin, valproic acid, etc. Hyperkinetic Movement Disorder Emergencies Myoclonus • Myoclonus is defined as a sudden, brief, lightning like movements that may be due to muscle contraction (positive myoclonus) or loss of muscle tone (negative myoclonus or ).

• The main clinical classification scheme are physiologic, essential, epileptic and symptomatic (Marsden at al, 1982). The physiologic classification based on EEG test results: Cortical myoclonus, subcortical/nonsegmental, segmental and peripheral Myoclonus. Hyperkinetic Movement Disorder Emergencies • Causes: i. Toxic/metabolic (most common hepatic and uremic , ii. Drugs (MAO inhibitors, SSRI, levodopa ,opiates, etc) iii. Cerebral anoxia may result in 2 distinct myoclonic syndromes: Myoclonus (generalized multifocal) and postanoxic myoclonus.

• Management - The etiology of the patient’s disorder is important consideration. The best symptomatic treatment strategy formulated on the basis of the physiology of the patient’s myoclonus.

• Treatment - Dopamine-depleting agent (tetrabenazine), benzodiazepine (clonazepam), anticonvulsant (leviteracetam, valproic acid). Hyperkinetic Movement Disorder Emergencies Dystonia • Dystonia is characterized by involuntary sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures.

• can be classified as focal, segmental, multifocal, hemidystonia or generalized, their etiologies are typically defined as primary (including genetic forms and idiopathic) or secondary.

• Drug induced acute dystonia (DID) is one of the commonest forms of secondary dystonia. The causative drugs are commonly antidopaminergics (typically, neuroleptics and antiemetics). Less frequently, other drug classes, such as anticonvulsants and antidepressants. Hyperkinetic movement disorder emergencies • Most cases occur in the first 72 hours of medication use with often dramatic symptoms, and more common in younger, male patients.

• The pathophysiologic mechanism is unclear (Dopamine, and cholinergic systems are involved).

• Clinical Presentation. Acute DID often affects the face and neck. Oculogyric crisis oromandibular dystonia, opisthotonos, , stridor, and dystonia of the trunk and limbs may also occur. Acute dystonic laryngospasm may prove fatal.

• Differential diagnosis. , tetanus, partial seizures, etc.

• Management. DID effectively treated with parenteral administration of anticholinergic medications; useful also clonazepam, promethazine. Hyperkinetic movement disorder emergencies Status dystonicus (SD) • SD also known as dystonic storm or dystonic crisis, refers to an acute worsening of generalized dystonia with severe, continuous, generalized movements. Dystonia can be tonic (i.e. sustained posturing) or phasic (i.e. irregular jerking).

• Status dystonicus is more common in the pediatric population, and males are more frequently affected. Dystonia secondary to is the most common underlying diagnosis.

• Dystonic storm tends to occur in patients with severe or poorly controlled dystonia at baseline, and one-third of events are unprovoked. Among provoked events, triggers include infection and medication change. Other possible precipitants include trauma, anesthesia, surgical procedures, stress, etc. Hyperkinetic movement disorder emergencies • Clinical Presentation. Severe generalized dystonia, fever, tachycardia, tachypnea or respiratory change, hypertension, sweating and autonomic instability.

• Other movement disorders such as chorea, ballism or myoclonus may accompany dystonia. Bulbar impairment such as dysarthria, dysphagia and respiratory failure are common, and these require close monitoring in the intensive care unit.

• Laboratory findings include leukocytosis, elevated serum CK, high C- reactive protein, myoglobinaemia, and myoglobinuria that may be severe enough to lead to renal failure and acidaemia. Hyperkinetic movement disorder emergencies • The differential diagnosis includes NMS, SS, malignant hyperthermia, acute dystonic drug reaction, etc.

• Management. The strategy of management differs in the acute and subacute periods. In the acute period patients should be admitted to the intensive care unit. Supportive measures include airway protection, sedation and pain control.

• Dystonia-specific treatment include anticholinergics, , benzodiazepines, dopamine receptor blockers, and DA. If these are not effective, typically used anesthetic agents intravenous , propofol, and barbiturates. • In refractory cases, surgical intervention (intrathecal baclofen pump placement, , pallidothalamotomy, or deep brain stimulation)may be considered. Hyperkinetic movement disorder emergencies Tic emergencies

Dr Steven Frucht (Department of Neurology Mount Sinai, School of Medicine, New York, USA), graciously granted permission to use the Tic emergencies video from the 3rd edition of Movement Disorder Emergencies submitted for publication in 2021.

Thank you