Toxicology – Movement Disorders

Definition

Abnormal movements can provide important clues to the cause of poisoning or medication toxicity.

Toxicologic movement disorders include:

• Akathisia
• Asterixis
• Myoclonus
• Ataxia
• Chorea
• Dystonia
• Dysarthria
• Fasciculations
• Nystagmus
• Drug-induced parkinsonism
• Rigidity
• Tremor
• Tardive dyskinesia

Recognition of the movement pattern + medication/exposure history + associated toxidrome is usually more useful than the movement abnormality alone.

Akathisia

Akathisia is a subjective feeling of inner restlessness accompanied by an inability to remain still.

Patients may:

• Pace
• Rock back and forth
• Repeatedly cross and uncross their legs
• Constantly shift position
• Report intense internal restlessness

It may be mistaken for anxiety, agitation, or worsening psychiatric illness.

Common drug causes include:

• Antipsychotics
• Metoclopramide and other dopamine-antagonist antiemetics
• Some antidepressants
• Other dopamine-blocking drugs

Symptoms often follow initiation or an increase in dose.

Asterixis

Asterixis is a negative myoclonus caused by brief interruptions of sustained muscle contraction.

When the arms and wrists are extended, there are intermittent lapses of posture producing the characteristic “flapping” movement.

Toxicologic causes include:

• Sedative-hypnotics
• Anticonvulsants
• Some psychoactive medications

Important nontoxic causes include:

• Hepatic encephalopathy
• Uremia
• Hypercapnia
• Other metabolic encephalopathies

Myoclonus

Myoclonus consists of brief, sudden, shock-like involuntary movements.

Unlike asterixis, classic positive myoclonus results from sudden muscle contraction.

Drug-related causes include:

• Serotonergic medications
• Opioids
• Anticonvulsants
• Lithium
• Some antidepressants
• Sedative-hypnotics

Myoclonus accompanied by hyperreflexia and clonus should raise concern for serotonin toxicity.

Ataxia

Ataxia is impaired coordination of voluntary movement.

Manifestations include:

• Unsteady gait
• Difficulty standing
• Poor limb coordination
• Dysmetria
• Impaired balance

Common toxicologic causes include:

• Ethanol
• Benzodiazepines
• Barbiturates
• Anticonvulsants
• Lithium
• Sedating antihistamines
• Other CNS depressants

Phenytoin and Ataxia

Phenytoin toxicity classically produces a progression of neurologic abnormalities such as:

• Nystagmus
• Ataxia
• Dysarthria
• Tremor
• Increasing CNS depression at higher exposure

These findings can be particularly useful when correlated with the clinical history and serum phenytoin concentration.

Chorea

Chorea consists of irregular, unpredictable, nonrhythmic movements that seem to flow randomly from one body region to another.

Very forceful choreiform movements are sometimes termed ballism.

Toxic or medication-related causes include:

• Dopaminergic medications
• Stimulants
• Antipsychotic-related movement disorders
• Lithium
• Carbon monoxide
• Manganese
• Some anticonvulsants

Metabolic causes include:

• Hypoglycemia or hyperglycemia
• Sodium abnormalities
• Calcium abnormalities
• Hyperthyroidism

Neurologic alternatives include Huntington disease and Wilson disease.

Dystonia

Dystonia consists of sustained or intermittent muscle contractions producing abnormal movements or postures.

Acute drug-induced dystonia commonly affects the:

• Face
• Eyes
• Jaw
• Tongue
• Neck

Manifestations include:

• Oculogyric crisis – forced upward or lateral eye deviation
• Torticollis – abnormal neck turning
• Retrocollis – backward neck extension
• Jaw spasm
• Tongue protrusion
• Blepharospasm
• Dysarthria
• Dysphagia
• Opisthotonic posturing

Acute Dystonic Reaction

The classic causes are dopamine D₂-receptor antagonists, especially:

• Antipsychotics
• Metoclopramide
• Prochlorperazine
• Other dopamine-blocking antiemetics

Acute dystonia can be dramatic and frightening but usually responds rapidly to an anticholinergic medication such as diphenhydramine or benztropine.

Rare laryngeal dystonia can compromise the airway and requires urgent treatment.

Dysarthria

Dysarthria is impaired articulation caused by poor motor control of the muscles involved in speech.

Speech may become:

• Slurred
• Slow
• Poorly articulated

Toxic causes include:

• Ethanol
• Sedative-hypnotics
• Anticonvulsants
• Lithium
• Other CNS-depressant drugs

Dysarthria often accompanies ataxia and nystagmus in sedative or anticonvulsant toxicity.

Fasciculations

Fasciculations are visible, brief contractions of individual motor units.

Important toxicologic causes include:

• Organophosphates
• Carbamates
• Nicotine
• Some stimulants
• Certain neurotoxins

In organophosphate poisoning, fasciculations represent nicotinic acetylcholine receptor overstimulation and may progress to:

• Muscle weakness
• Paralysis
• Respiratory failure

When accompanied by miosis, bronchorrhea, salivation, sweating, and diarrhea, a cholinergic syndrome should be strongly suspected.

Nystagmus

Nystagmus is rhythmic involuntary movement of the eyes.

Toxicologic causes include:

• Sedative-hypnotics
• Anticonvulsants
• Lithium
• Phencyclidine (PCP)
• Ethanol

The direction and pattern can sometimes provide additional clues.

PCP and Nystagmus

PCP intoxication is classically associated with:

• Horizontal, vertical, or rotatory nystagmus
• Agitation or unusual behavior
• Analgesia
• Hypertension
• Tachycardia
• Ataxia

Vertical nystagmus in an intoxicated patient is an especially useful clue, although it is not completely specific.

Parkinsonism

Drug-induced parkinsonism resembles Parkinson disease and may produce:

• Bradykinesia
• Rigidity
• Tremor
• Shuffling gait
• Reduced facial expression
• Postural instability

The major medication mechanism is dopamine D₂ receptor blockade.

Common causes include:

• Antipsychotics
• Metoclopramide
• Prochlorperazine
• Other dopamine antagonists

Toxic Parkinsonism

Toxic exposures associated with parkinsonian syndromes include:

• Manganese
• Carbon monoxide
• Methanol
• Carbon disulfide
• MPTP

MPTP is particularly notable because its toxic metabolite selectively damages dopaminergic neurons in the substantia nigra and can produce profound parkinsonism.

Rigidity

Rigidity is increased resistance to passive movement.

In toxicology, marked rigidity accompanied by hyperthermia and altered mental status should immediately raise concern for:

• Neuroleptic malignant syndrome
• Serotonin syndrome
• Malignant hyperthermia
• Severe MAOI toxicity

The accompanying neuromuscular findings help differentiate them.

NMS vs. Serotonin Syndrome

Neuroleptic malignant syndrome

• Dopamine blockade or withdrawal of dopaminergic therapy
• Usually slower onset
• Severe generalized rigidity
• Hyporeflexia or relatively normal reflexes
• Hyperthermia
• Autonomic instability
• Altered mental status
• Elevated CK

Serotonin syndrome

• Serotonergic exposure
• Usually rapid onset
• Hyperreflexia
• Clonus
• Tremor
• Agitation
• Diaphoresis
• Hyperthermia
• GI hyperactivity may occur

The presence of clonus strongly favors serotonin toxicity.

Tremor

Tremor is a rhythmic oscillating movement.

It may be classified as:

• Resting
• Postural
• Kinetic/action

Important toxicologic causes include:

• Lithium
• Valproate
• Stimulants
• Caffeine
• Beta₂-adrenergic agonists
• Theophylline
• Thyroid hormone excess
• Heavy metals
• Alcohol or sedative withdrawal

The pattern of tremor alone rarely identifies the toxicant, so associated findings are essential.

Lithium

Lithium toxicity can produce multiple movement abnormalities, including:

• Coarse tremor
• Ataxia
• Dysarthria
• Myoclonus
• Fasciculations
• Nystagmus
• Chorea in severe cases

Progressive neurologic abnormalities in a patient taking lithium should prompt assessment for toxicity.

Tardive Dyskinesia

Tardive dyskinesia is a delayed hyperkinetic movement disorder associated primarily with prolonged exposure to dopamine receptor-blocking medications.

Typical manifestations include:

• Lip smacking
• Chewing movements
• Grimacing
• Tongue protrusion
• Repetitive facial movements
• Limb or trunk movements

Unlike acute dystonia, tardive dyskinesia usually develops after chronic exposure.

Symptoms can persist after the responsible medication is discontinued.

Tardive Dystonia

Tardive dystonia is another delayed complication of chronic dopamine receptor blockade.

It causes sustained abnormal postures and may involve:

• Neck
• Trunk
• Limbs
• Cranial muscles

It should be distinguished from an acute dystonic reaction, which generally appears shortly after beginning or increasing a dopamine-blocking medication.

Extrapyramidal Syndromes

A useful framework for dopamine-blocking medication effects is:

Hours to days

→ acute dystonia

Days to weeks

→ akathisia

Weeks to months

→ drug-induced parkinsonism

Months to years

→ tardive dyskinesia/tardive dystonia

The timing is approximate and overlap can occur.

Diagnostic Approach

When an abnormal movement occurs, determine:

• Exact type of movement
• Time of onset
• Recent medication changes
• Prescription and nonprescription drug exposure
• Withdrawal history
• Occupational or heavy-metal exposure
• Associated mental-status changes
• Autonomic findings
• Temperature
• Reflexes and clonus

The time relationship between drug exposure and movement onset is particularly useful.

Laboratory Evaluation

Testing should be guided by the suspected cause.

Possible investigations include:

• Glucose
• Electrolytes
• Calcium and magnesium
• Renal function
• Liver function
• Creatine kinase
• ECG

Targeted testing may include:

• Lithium concentration
• Anticonvulsant concentrations
• Heavy-metal testing when exposure is plausible
• Other drug-specific studies

Broad urine toxicology screening is usually less useful than targeted evaluation.

Neuroimaging

Movement disorders should not automatically be attributed to poisoning.

Brain imaging may be necessary when findings suggest:

• Stroke
• Intracranial hemorrhage
• Structural CNS disease
• Trauma
• Focal neurologic abnormalities

Management Principles

Treatment depends on the underlying syndrome.

General measures include:

• Stop or modify the causative medication when appropriate.
• Correct glucose and electrolyte abnormalities.
• Treat hyperthermia.
• Control seizures.
• Provide supportive care.

Important syndrome-specific treatments include:

Acute dystonia

→ diphenhydramine or benztropine

Akathisia

→ remove/reduce the causative agent when appropriate; selected symptomatic therapies may be used

Serotonin syndrome

→ discontinue serotonergic drugs, benzodiazepines, cooling, and selected use of cyproheptadine

NMS

→ discontinue dopamine antagonist, supportive care/cooling, with syndrome-specific therapy in severe cases

Cholinergic fasciculations

→ atropine for muscarinic manifestations plus pralidoxime in significant organophosphate poisoning

Tardive Dyskinesia Treatment

Management includes reassessing the responsible dopamine-blocking medication.

VMAT2 inhibitors such as valbenazine or deutetrabenazine are established treatments for clinically significant tardive dyskinesia.

Routine anticholinergic treatment may worsen tardive dyskinesia, even though anticholinergics are useful for acute dystonia and drug-induced parkinsonism.

Key Points

• Abnormal movements can provide important toxicologic diagnostic clues.
• Akathisia = inner restlessness with inability to remain still.
• Asterixis = brief loss of postural tone; myoclonus = sudden shock-like movement.
• Ethanol, sedatives, anticonvulsants, and lithium commonly produce ataxia.
• Dopamine-blocking antipsychotics and antiemetics commonly cause acute dystonia, akathisia, and parkinsonism.
• Acute dystonia commonly involves the eyes, jaw, tongue, and neck and usually responds to anticholinergic treatment.
• Fasciculations + excessive secretions + miosis strongly suggest cholinergic toxicity.
• PCP classically produces prominent nystagmus, including vertical nystagmus.
• Rigidity + hyperthermia should prompt consideration of NMS, serotonin syndrome, or malignant hyperthermia.
• Clonus and hyperreflexia strongly favor serotonin syndrome over NMS.
• Lithium toxicity can produce coarse tremor, ataxia, dysarthria, myoclonus, and other neurologic abnormalities.
• Tardive dyskinesia is a delayed complication of chronic dopamine-receptor blockade and may persist after drug discontinuation.
• Always consider metabolic and structural neurologic disease before assuming that an abnormal movement is toxicologic.