Peter J. Barbour, MD
DESCRIPTION
- Dystonia: Involuntary muscular contraction:
- Leading to sustained postures
- With or without athetoid-like movements
- Dystonic reaction (DR): Acute dystonia due to an identifiable cause
EPIDEMIOLOGY
Incidence
- Not clearly defined
- 30–40% exposed to classical antipsychotics
- Related to potency, dose, rate of titration
- May also occur with other agents
RISK FACTORS
- Previous DR with exposure to agent
- Predictors: In-patients receiving neuroleptics:
- Age:
- Children and young adults highest risk
- Sex: Males greater than females (2:1)
Genetics
- Higher incidence of DR among relatives of patients with idiopathic or torsion dystonia
- Cytochrome P450 2D6 polymorphism (1)[C]
GENERAL PREVENTION
- Avoidance/caution with agents that most commonly induce DR in those at risk
- Young adult males with psychiatric illness
- Neuroleptics given in setting of cocaine use
PATHOPHYSIOLOGY
- The pathophysiology of DR is not known.
- DR appears to be mediated by:
ETIOLOGY
- Agents implicated (see “Additional Reading”)
- Dopamine-blocking antipsychotic agents:
- Butyrophenones, phenothiazines, benzamides
- Dopamine-blocking antinausea agents:
- Serotonin agonist anxiolytic agents:
- Serotonin agonist antimigraine agents:
- Selective serotonin reuptake inhibitor
- Tricyclic antidepressants
- Monoamine oxidase inhibitor antidepressants
- Diphenhydramine
- Note: Diphenhydramine is a treatment for DR
- Antihistamine/decongestant cold prep
- Erythromycin (single case report)
- Illicit drugs:
- Cocaine: Especially with neuroleptics
- Ecstasy
- Anesthesia
COMMONLY ASSOCIATED CONDITIONS
- Possible increased risk associated with neuroleptic use and the following:
- Parkinson's disease:
- Dopamine excess and deficiency
- DR observed in the appropriate setting: Exposure to agent known to cause DR
- Movements associated with DR: (2)[C],(3)[C]
- Forced eye deviation with rotation of head up and back [oculogyric crisis (OGC)]
- Blepharospasm
- Torticollis
- Trismus
- Dysarthria
- Opisthotonus
- Pisa syndrome: (4)[C]
- Tonic lateral flexion of the trunk with backward rotation (neuroleptic induced)
- Laryngeal/pharyngeal spasm (rarely)
- May interfere with breathing
- Implicated in sudden death with neuroleptics
- Symptom onset:
- 2–24 hours after exposure, 100% by 9 days
- Immediately with parenteral administration of an antiemetic such as prochlorperazine
- Duration of reaction:
- Variable: May last days waxing and waning
- Distribution of signs:
- More generalized in children
- More circumscribed in adults
- Region of the body involved may be constant or fluctuate during a DR
- Associated symptoms may be painful.
HISTORY
- History is directed towards the identification of the offending agent.
- Identify history of prior reactions
- Identify concomitant psychiatric history
- History of endocrinopathy
- Review exposure to:
- Prescription and non-prescription drugs
- Illicit drugs
- Family history of torsion dystonia
PHYSICAL EXAM
- Observe for movements associated with DR
- Look for signs of underlying disorders that may mimic DR
- Parkinsonism: Rigidity, bradykinesia, rest tremor
- Seizure: Tongue bite, confusion
- Attempt to precipitate the dystonia if history suggests (task-specific behaviors) writing – writer's cramp, walking – foot dystonia; Parkinsonism
DIAGNOSTIC TESTS AND INTERPRETATION
Lab
Initial Lab Tests
- Investigation is tailored to setting.
- DR immediately after receiving a neuroleptic agent, no investigation may be indicated.
- Where the offending agent is not known but strongly suspected, consider drug screen.
- If the tonic posture (opisthotonus) or other findings suggest a non-drug related cause (as in the setting of renal dialysis), search for metabolic or infectious cause.
- Unexplained movement disorder, especially in a young patient, testing may include:
- Ceruloplasmin, serum copper, slit-lamp examination (to rule out Wilson's disease)
- Creatine kinase, myoglobin, glucose, lactate, pyruvate, uric acid, creatine, liver function studies, ESR, antinuclear antibody screen (see “Dystonia,” “ Torticollis”).
Imaging
Initial Approach
If history and physical examination suggest the possibility of a focal underlying process, such as stroke, MRI of the brain is indicated. However, for DR that is obviously drug-induced, imaging is not required.
Diagnostic Procedures/Other
If seizure remains a question on a clinical basis, electroencephalography is indicated.
Pathological Findings
DR is a pathophysiologic reaction to a substance. No anatomic pathological findings are defined.
DIFFERENTIAL DIAGNOSIS
- Secondary dystonias
- Sudden onset:
- Post-traumatic cervical dystonia
- Parkinson's disease: Peak dose dystonia – too much dopamine. Early morning foot dystonia; too little dopamine
- Post-encephalitic parkinsonism (early 20th century avian flu, Von Economo's encephalitis, associated with OCG)
- Insidious onset:
- Primary dystonias: Task specific (writer's cramp)
- Seizure: The signs of DR are dramatic, frightening, may be mistaken for seizure.
- DR is not associated with altered consciousness or postictal confusion.
- Simple partial seizures that are not associated with loss of consciousness may still pose a problem for differentiation.
- Paroxysmal dyskinesia: Poorly understood disorders associated with sudden movements that may include dystonia.
- Paroxysmal dystonic choreoathetosis
- Paroxysmal exertion-induced dyskinesia
- Transient paroxysmal dystonia
- Torticollis of infancy
MEDICATION
First Line
- May be self-limiting
- Moderate-to-severe reactions:
- Adults: Benztropine 1–2 mg IV or IM, repeat in 20 minutes if no effect (3)[C]. Maximum cumulative dose: 6 mg (2)[C]. DR may return; therefore oral anticholinergic for 4–7 days in tapering dose
- Adults: Diphenhydramine 1–2 mg/kg up to 100 mg slow IV or IM, followed by several days of oral treatment (5)[C]
- Children: Benztropine 0.2 mg/kg to max 1 mg IV or IM, may repeat once (wait 30 minutes if IM). Continue same dose orally b.i.d., for up to 48 hours (5)[C]
- Contraindications:
- Known hypersensitivity to these medications
- Diphenhydramine should not be used in neonates or nursing mothers.
- Benztropine is contraindicated in patients less than 3 years of age.
- Precautions:
- Antihistamines (diphenhydramine) caution in patients with asthma, increased intraocular glaucoma, cardiovascular disease, hyperthyroidism, benign prostatic hypertrophy, and bladder neck obstruction.
- Acute dystonia related to Parkinson's disease: The acute dystonic cramp may respond to adjustment in medication.
Second Line
- Moderate-to-severe reaction
- Promethazine 25–50 mg IV or IM (5)[C]
- Diazepam 5–10 mg IV (reserved for patient who incompletely responds to above) (5)[C]
ADDITIONAL TREATMENT
General Measures
- Reassurance
- Observe for airway compromise
Issues for Referral
Laryngeal/pharyngeal involvement
SURGERY/OTHER PROCEDURES
- Not indicated for DR
- Late-occurring dystonia, tardive dystonia, in the setting of chronic neuroleptic drug exposure, consider chemodenervation with botulinum toxin (6)[C]
IN-PATIENT CONSIDERATIONS
Initial Stabilization
Monitor airway and breathing
Admission Criteria
Consider hospitalization for observation as DR may recur and laryngeal/pharyngeal involvement is possible.
IV Fluids
DRs are frightening, dramatic, may be painful, requiring IV access.
Nursing (for DR Involving Head & Neck)
- Monitor heart rate, respiration, blood pressure and pulse oximetry until DR resolves
- Begin IV D5W at KVO
- For DR compromising swallow/breathing
- NPO until DR resolves
- Bed rest with head of bed elevated until DR resolves
Discharge Criteria
- Parenteral medications are usually effective within 20 minutes. The effect may wear off with recrudescence of DR, necessitating a second injection.
- Discharge after period of observation with no recurrence of DR.
FOLLOW-UP RECOMMENDATIONS
- Treatment of DR may include:
- Dose adjustment of the offending agent
- Discontinuation of the offending agent
- Administration of medication to abort this reaction if it recurs
- Reassurance: DR frightening and painful
- Patients who have experienced acute DRs are at higher risk for future reactions.
- Prophylaxis: May be considered if long-term neuroleptic use is required.
- Consider the following agents: Anticholinergics, Antihistamines, Amantadine
PATIENT EDUCATION
- Primarily regarding agents to avoid instructions in case of recurrence.
- Mild DR, consider oral treatment:
- Diphenhydramine 50 mg PO t.i.d. for several days
- Severe DR
- Return for further treatment (IV required)
PROGNOSIS
DR, due to neuroleptic agents, is self-limited and does not require ongoing treatment once the offending agent is removed and DR resolves.
COMPLICATIONS
Failure to respond to several doses of parenteral anticholinergic medication should prompt additional evaluation (see above).
Google Scholar: Dystonic reaction “suspected agent,” such as cocaine, propofol, ecstasy.
SEE-ALSO
