MOVEMENT DISORDER EMERGENCIES

Andradi S.
Department of Neurology, University of Indonesia,
Jakarta
 Emergency

MD

Emergency Classical course

 Definition

Movement Disorder
Movement disorders (MD) is an abnormal movement
characterized by involuntary movement or loss of control of
voluntary movement.

Movement Disorder Emergency(MDE)

MDE is a MD, which usually develop slowly progressively, in certain
condition, appears with acute or subacute onset, or progresses
rapidly, leading to disease deterioration, even potentially fatal, if
early diagnosis and prompt treatment are not adequatey done.
.
 Types of Movement Disorder Emergency (MDE)
I. PARKINSON DISEASE-RELATED MDE
1. “ Super OFF” phenomenon
2. Parkinsonism-hyperpyrexia and dyskinesia-hyperpyrexia syndromes
3. Acute parkinsonism
4. Acute psychosis in Parkinson's disease

I I. ACUTE DRUG REACTIONS

1. Acute dystonia
2. Neuroleptic malignant syndrome
3. Serotonergic syndrome
4. Malignant hyperthermia

III. ACUTE EXACERBATION OF CHRONIC MDs

1.. Status dystonicus
2. Neurological and orthopedic complications of dystonia and pseudodystonia
3. Laryngeal dystonia in multiple system atrophy and other conditions
4. Tic status and neurological complications of tics
5. Wilson's disease emergencies
6. Others conditions
IV. ACUTE CHOREA AND HEMIBALLISM-HEMICHOREA
V. Stiff-person syndrome
VI. Lethal catatonia

V. Stiff-person syndrome
 I. Parkinson’s disease-related MDE

I. 1. “Super OFF" phenomenon

- This complication of PD rare
- Once occures it will be frightening to the patient and the family. It lasts for
some minutes to hours.
- The motor symptoms deteriorate more than usual “OFF” symptoms
during motor fluctuation experienced by the patient.

There are two kinds of “Super OFF” phenomenon::

1. Beginning-of-dose, before therapeutic plasma level of

levodopa is attained.
2. End-of-dose, after the level is attained.
 “Super OFF” phenomenon

Therapy
Clozapine
- Clozapine could inhibit the inhibitory action of low plasma levodopa
level which leads to an apparent antiparkinsonian effect.
- These episodes may be present only in subgroups of PD patients
I.2. Parkinsonism-hyperpyrexia syndrome (PHS) and dyskinesia-
hyperpyrexia syndrome (DHS)
• Parkinsonism-hyperpyrexia syndrome also known as neuroleptic
malignant-like syndrome,
• A rare complication of PD
• Characterized by hyperthermy, autonomic dysfunction, consciousness
deterioration, severe rigidity, increased serum creatine kinase ( CK) level.
• Triggering factors: infection, reduction of dopaminergic agent dose, hot
weather or dehydration.
• Complications : DVT, pulmonary embolism, aspiration pneumonia, renal
failure.
• Terapi
- Infusion of fluid
• - Antipyretic
- Levodopa or dopamine agonist
Dyskinesia-hyperpyrexia syndrome (DHS)
- - Severe dyskinesias (dyskinetic status) → muscle exhaustion →
rhabdomyolysis, hyperthermia and confusion.
- Shares some of the clinical characteristics of PHS
difference: PHS → rigidity dominates
DHS → dystonia dominates
- Treatment
- Contradictorily to PHS --> reduce the dosage of dopaminergic drugs,
particularly dopamine agonists.
I.3. Acute Parkinsonism
- Developes within hours to days
- Cause :
- the most common cause is the use of dopamine blocking agent,
such as neuroleptic and antiemetic
- Other causes:
- ischemic-hypoxic encephalopathy,
- intoxication (pesticide, organophosphate),
- CO
- cytostatic ( cyatosine arabinoside, cyclophosphamide, and
amphotericin),
- infection (von Economo’s encephalitis lethargica, Japanese B
encephalitis , neurocysticercosis)
- subdural hematom, cerebral tumor
Therapy
- Treat causative factor
- Dopaminergic agent
I.4. Acute psychosis in PD
Relatively common in advanced PD
- Often associated with cognitive impairment
- Acute onset related to or triggered by anti-PD drugs, such as levodopa,
dopamine agonist, anticholinergic, amantadine, COMT-I, and MAOB-I.
- Comorbidities which may play role: UTI, respiratory tract infection,
mrtabolic and neurologic disorder.
-Clinical manifestations
- Visual hallucination, delution, confusion, psychomotor agitation.
. - Terapi
- Treat related comorbid
- Withdraw gradually potential antiparkinson anticholinergic, MAOB-I,
COMT-I, DA agonist, amantadine.
- Antipsychotic agent is often needed, including second gentieration
antipsychotic clozapine, quetiapine, risperidone, and olanzapine.

•
II. Acute Drug Reaction
• 1. Acute Dystonia
• . - Types: local, segmental, nultifocal, hemidystonia, general.
• - Etiology:
• 1. Primary ( genetic, idiopathic)
• 2. Secondary: most common →Drug-induced , acute and tardive dystonia
•
• Drug-induced Dystonia (DID)
• - Drugs commonly induce dystonia: antidopaminergic (haloperidol, risperidone,
• olanzapine), and antiemetic. Rarely anticonvulsant, antidepressant.
• -
• - Muscle contraction may occur soon after taking one dose, within some days
• during therapeutic dose, after increasing the dose, or overdose.
•
• - Sumptoms appear mostly in the first 72 hours after taking the drug. The
• symptoms are often dramatic, particularly in children
•
• - The risk factors for DID : young male, history of similar reaction, cocaine user,
• mood chsnges and metabolic disorder (hypokalemia, dehydration, hypothyroid)
 DID
• Cnical Symptoms
- Dystonia of muscles at :
Craniocervical region →blepharospasm and bucokinguomandibular dystoniia,
Oculocgyric crisis→ contraction of m. rectus superior muscle →upward
conjugate deviation
- One specific form of DID is vocal cord dystonia→laryngeal spasm → upper
raspiratory tract obstruction
The symptom appears at the boginning of treatment or at the time of
increasing the dose

Tardive dyskinesias
This can be an MD Emergency espacially in the socalled “withdrawal-
emergent”dyskinesia , i.e. severe dyskinesia after cessation of neuroleptic.
 DID
For oculogyric
Differential Diagnosis
Differential diagnosis includes neurologic and metabolic disorders , such as
focal epilepsy, meningitis, tetanus, electrolyte imbalance and strychnin
intoxication.

Therapy
- Anticholinergic _(Biperoden) 5 mg IV or IM, followed by oral route , for
main tanance, for one week.
- Promethazine 50 mg IM
- For oculogyric crisis : clonazepam 2 mg orally, or difenhidramin 25 – 50 mg
IM.
- Prophylaxis with anticholinergic or amantadine is still controversual , and is
not recommended to be used routinely.
2. Neuroleptic malignant syndrome (NMS)
Neuroleptic malignant syndrome (NMS) is an idiosynchratic reaction of medication with
antidopaminergiac agent manifesting with characteristic clinical and paraclinical symptoms.
- It is caused by classic neuroleptic drugs, howeber, with th3e frequent use of atypical agent it may also
involved.
- NMS can also be caused other dopamune blocker, or following abrupt cessation of dopaminergic.
. - Symptom appears in two weeks after neginning treatment or upon changing the dose.
Risk factors
Rapid dose increasing - depot formulation, - male
- Young age - SSRI - high temperature
- Hyponatremia - Dehydration - physical exhaustion
- Mental retardation - extrapyramidal syndrome - psychomotor agitation
- Prior history of NMS.
- May occur at any age from 9 months to 78 years old, with mean age 4-5 deade.
Mortality
- Relatively high, 20-30%.
- Most survivors live without many equelae, however, some cases experience
cognitive impairment and motor deficit like rigidity, tremor, and dystonic
contracture.
.
•
 Neuroleptic Malignant Syndrome
Diagnosis
diagnostic criteria:
1. Hipertermi
2. Rigiditas
3. Mental changes
4. Dysautonomia
• These criteria may be assciated with other symptoms, such as rest
and/or action tremor, dystonia, chorea, myoclonus, seizure, ataxia,
hyporeflexia, and extensor plantar reflex.
• - Laboratory findings: elevated serum creatine kinase, liver and renal
dysfunction, abnormal kemostatic test, leucocytosis, electrolyte
imbalance, proteinuria, rhabdomyolysis with myoglobinuria.
Differential Diagnosis
The most important are serotonergic syndrome, malignant hyperthermia
and malignant catatonia. Other condition is abrupt cessation of
intrathecal administration of baclofen → acute NMS
 Neuroleptic Malignant Syndrome
• Terapi
Therapeutic approach:
Early recognition→exclude DD→ witgdraw related drug → intervention,
pharmacologi cand nonpharmaologic.
Therapeutic option is determined by the severity of NMS and additional
complication.
- Pharmacologic intervention is aimed to
- minimize rigidity with bensodiazepine
- delete excessive dopaminergic blockade with bromocriptine,
levodops or amantadine, and control agitation.

For patient using neuroleptic,

- The drug shoule be withdrawn for at least 2 weeks after treatment of acute phase
- Retreatment with neuroleptic, beginning with low dose,Increasing slowly.
while observing the appearance of dehydration and reappearance of NMS
symptoms
c. Serotonergic syndrome (SS)
- Serotonin syndrome (SS) is potentially fatal, due to the combined use of
2 or more drugs which increase the activity of serotonin or which
increase the concentration of serotonin in the CNS.

Clinical symptoms
- Acute agitation - mental changes - myoclonus
- Ataxia - postural instability - rigidity
- dysautonomia (diaphoresis, fever, diarrhoe, tachycardia, hemodynamic
- instability)
Diagnosis
Diagnosis criteria:
At least three of the followings (after exclusion of other causes) :
1. Acute onset, sometimes gradual or repetitive
2. Cognitive impairment
3. Behavioural disorder
4. Tremor
5. Postural instability
,
Serotonic Syndrome (SS)
- Not an idiosynvgratic reaction → can be predicted.
- Cause
- Drug/drugs combination → overstimulation of serotonin (5-HT1A) receptor:
- SSRI
- Serotonin metabolism inhibitor (MAO -Iinhibitor)
- Serotonin precursor (L-tryptophan)
- Serotonin release enhancer (amphetamine, cocaine, fenfluramine)
- Serotonin agonist (risperidone , sumatriptan, ergotamine)
- nonspecific enhancer of serotonin activity (lithium and electroconvulsive
therapy (ECT)

-Example: SSRI + one of serotonergic.

 Serotonic Syndrome

Diagnosis
Diagnosis is based on clinical findings:
Anamnesis
- History of use of drugs directly or indirectly affect serotonergic
system.
Clinical symptoms
- - Mental changes
- Autonomic instability
- - Motoric disorder: tremor, mioclonus, ataxia, hyperreflexia.
- . Occationally seizure, renal failure, and DIC in severe cases.
Laboratory examination
Examinations for metabolic disorder:
- metabolic acidosis
- rhabdomyolysis
- elevated aminotransferase serum , creatine and leucocyte.
Therapy SS
- Principle of therapy: prevention, early detection, and acute intervention.
- Main treatment: withdraw the resposible drug →symptom reduction
- For the remaining symptoms→ 5-HT receptor blocker ( cyproheptadine , methyserfide)→
may shorten SS duration.
- Other potential drugs: bensodiazpine, chlorpromazine, and propranolol
- Supportive therapy: tretment of seizure, arrhythmia, DIC, rigidity, hyperthermia
Prognosis
- -In general good. Providing detected early and adequately managed.
- - Mortality rate 2.4 - 12%
- Reinstitution of serotonergic must be with care →start low go slow
d. Malignant hyperthermia (MH)
- Malignant hyperthermia (MH) is a disorder of skelet, which occur when such
patient is exposed to anesthetic agent as a trigger.
- Rarely encountered but potentially fatal with mortality rate > 80% in
1970th.better
Currently with better D/ awareness and management →mortality rate < 5%
Clinical symptoms
Early : muscle spasm, general muscle rigidity, tachycardia,hypercapmia, hypoxia,
combined metabolic – respiratory acidosis.
Late: : hyperthermy, hypotension, , rhabdomyolysis, acute renal failure, cardiac
arrhythmia, circulatory failure.
- Episode related to inhalation anesthetic agemt or depolarizing muscle relaxants.
-Clinical symptoms result from uncontrolled influx of Ca through muscle
membrane.
-Genetic factor in half of the family of patient. autosomal dominant link at gene
encoding intracellular Ca2+ release channel receptor (type 1 ryanodine receptor)
in skelet miscle.
Therapy MH
- immediate administration of dantrolene 2 mg/kg, repeat every 5
minutes until the cardiac and respiratory systems are stabilized
- Stop administration of volatile anesthesia, hyperventilated
with 100% oxygen at maximum fresh gas flow
- Ice packs, cooling blankets and fans may also be used to help
reduce body temperature.
• Stop administration of trigger agents
• Anesthesia should be continued using intravenous opioids,
sedatives, and, if necessary, nondepolarizing muscle relaxants.
 III. ACUTE EXACERBATION OF CHRONIC MDS
I

a. Status dystonicus
- Status dystonicus (SD), also called dystonic storm
- Rare, but life threatening
- Related to primary and secondary dystonia.
- Clinical symptoms
- Triggered by trauma, surgical procedure, infection, fever
the use, withdrawal, or rapid changes of usage of drugs
as lithium, tetrabenazine, and clonazepam.
- Paiful muscle contracture → disturb respiration , hyperpyrexia,
dehidration, respiratory insufficiency,
rhabdomyolysis, acute renal failure.
a. Status dystonicus

Terapi
- Refractory to pharmacotherapy, no definitive management consensus.
- Strategy: - combination of drugs, may need surgical intervention.
- - Immediatey restore fluid balance,analgesic,antipyretic
- Empirically: trabenazine, baclofen, chlormethiazole, anticholinergic, dopamine receptor
lblocker (haloperidol,pimozide) ,antikonvulsant (carbamase, pinprimidone, and valproic
acid) levodopa, acetazolamide, benzodiazepines (midazolan, clonazepam and
diazepam), deep sedation with propofol, barbiturate anesthesia and muscle
blockers

SD is a potentially life threatening complication and its course and outcome is highly
variable,
b. Neurological and orthopedic complications of
dystonia and pseudodystonia
Severe dystonia ( generalized dystonia)

contractures

neurological and orthopedic complications

- Spinal cord compression (particularly cervical
myelopathy)
- Lesions to nervous plexi or peripheral nerves.
- Severe and disabling scoliosis
Pseudodystonia
Encompasses conditions that mimic dystonia, including:
- infectious and neoplastic torticollis
- atlantoaxial rotatory subluxation
- localized tetanus.
- Infectious torticollis secondary to pharyngitis,
tonsillitis or retropharyngeal abscess
(Grisel's syndrome)
May present acute or subacutely,.
c. Laryngeal dystonia in multiple system atrophy and other conditions
Multiple system atrophy (MSA)
a form of atypical parkinsonism
MD (either parkinsonism or cerebellar ataxia)
+
Dysautonomia.

Some of these patients → posterior cricoarytenoid muscles dysfunction,

either dystonia or paresis.→ laryngeal stridor, predominantly
during the night → upper airway obstruction→ increased risk of sudden
death ..
c. Laryngeal dystonia in multiple system atrophy
and other conditions
• Acute laryngeal dystonia
- A very rare form of task-specific dystonia
(Gerhardt's syndrome)
- Spasm of the adductor muscles of the vocal cord during
inspiration
- while performing other activities, such as speaking.
→ severe stridor with risk of upper airway obstruction.
- Therapy: - Diphenhydramine (25 mg to 50 mg) IV .
- Occasionally, tracheostomy or even botulinum toxin
injection is necessary
d. Tic status and neurological complications of tics
chronic motor, vocal tics or Tourette's syndrome

continuous disabling tics

cannot be suppressed

- interfering dramatically with daily life activities

- cardiorespiratory difficulties
- autonomic signs
- rhabdomyolysis

tic status
MD emergency.
 Tic Status
Triggering factors
- withdrawal of drugs used to treat tics (e.g., haloperidol or clonidine)
- extreme reactive stress
. Therapy
- readministration of previously withdrawn drug
- dosage increase of previous therapy,
- addition of benzodiazepines
- switching to second generation antipsychotics.
- discontinuation of agents know to induce tics, such as methylphenidate
- Botulinum toxin injections , particularly in patients with malignant vocal tics

• violent neck motor tics → may cause neurological complications like cervical
myelopathy
e. Wilson's disease emergencies
- Wilson's disease (WD) is an autosomal recessive disease of
Copper metabolism caused by mutations in the ATP7B gene.
- The most common neurologic symptoms are :
tremor, dysarthria, dystonia, ataxia and parkinsonism.
- Emergencies in WD are related to hepatic involvement (fatal acute
or fulminant liver failure) or sudden worsening of neurological
symptoms, particularly after use of D-penicillamine.
•
f. Others conditions
- Other several clinical conditions can present as MD
emergencies :
- hypocalcemia→ Tetanic muscle spasm
- tetanus
- rabies -
- strychnine toxicity
.
IV. ACUTE CHOREA AND HEMIBALLISM-HEMICHOREA
• Hemiballism
- ia relatively rare hyperkinetic disorder,
- characterized by: irregular, wide amplitude, vigorous involuntary
movements of the proximal limbs, and associated axial muscles
•. Ballism is considered a very severe form of chorea, in which the
movements have a violent, flinging quality..
Frequently, hemiballism is associated to hemichorea
→ hemiballism-hemichorea (HBC)
- Causes:
-metabolic disorders (nonketotic hyperglycemia, hypoglycemia,
hyperthyroidism),
- Sydenham's chorea - systemic lupus erythematosus
- antiphospholipid syndrome post-operative cardiac surgery
, -

- Infectipn - tumors
- multiple sclerosis. - nonketotic hyperglycemia
V. Stiff-person syndrome (SPS)
- a rare neurological disorder characterized by the presence of
fluctuating muscle rigidity and spasms of the trunk and more
proximal body parts.
- an emergency with severe pain and spasms of the lumbar paraspinal
muscles and lower limbs.
- The spasms, often associated with intense pain, typically begin with an abrupt
jerk→followed by tonic activity →slowly subsides over seconds to minutes.
- Rarely, these spasms last days (status spasticus).
-The affected muscles are typically extremely hard to palpation with a board-like
appearance → hyperlordosis.
- Muscle spasms can occur spontaneously or be provoked by noise or movement.
f. Stiff-person syndrome
Clinical symptom
- The spasms may be so forceful
→femoral fractures
→ joint subluxations
→ even herniation of abdominal contents.
- Paroxysmal autonomic dysfunctions:
transient hyperpyrexia, diaphoresis, tachypnea, tachycardia, pupillary
dilation and arterial hypertension
- Rhabdomyolysis a complication of the excessive muscle contractions in SPS.
Stiff-person syndrome
Clinical symptom (cont’d)
- Sudden death can occur due to an acute autonomic failure
- In a significant number of cases, SPS is believed to be mediated by autoantibodies
to glutamic acid decarboxylase (anti-GAD)→ limit the gamma amino-
butyric acid (GABA) neuronal activity→ lower the threshold for muscle
spasms, other neurologic and psychiatric features of the disorder.
- SPS with elevated serum anti-GAD levels may occur with other
autoimmune disorders, including diabetes mellitus, Graves' disease,
Hashimoto's thyroiditis and pernicious anemia.
- Ten percent of cases with normal levels of this antibody may be related to
autoantibodies against amphiphysin which commonly represent a
paraneoplastic syndrome related to breast cancer, mediastinal tumors,
small cell lung cancer, Hodgkin's disease and colon cancer56.
 Stiff Person Syndrome

Therapy
- Based on the use of drugs that promote GABAergic inhibition, for example,
benzodiazepines (diazepam and clonazepam) and baclofen.
- Benzodiazepines →abolish the excessive motor unit activity.
- Oral baclofen → relatively modest relief
- Intrathecal baclofen →much more effective.
- Antiepileptic drugs ( valproic acid, levetiracetam and gabapentin) →
variable degrees of benefit.
VI. Lethal /Malignant Catatonia
- uncommon and probably under-recognized
- usually occurs in the setting of schizophrenia
may also follow infections as meningitis and encephalitis, head trauma,
drug intoxication and metabolic disturbances, for example, uremia,
porphyria and Wernicke's encephalopathy.
clinical symptoms,
- hyperthermia, autonomic instability and severe rigidity,
- if prolonged → exhaustion, coma, renal failure,
cardiovascular collapse and death. Violent behavior, including
unprovoked assaults and suicide attempts. , may occur
occasionally ,m
•
 Lethal/Malignant Catatonia
Diagnosis
- clinical, and no paraclinical tests confirm the
specific diagnosis..
Therapy
- IV benzodiazepines, barbiturates
.- Dantrolene, bromocriptine, amantadine and
anticonvulsants (e.g., carbamazepine) may be
tried.
•