What is the appropriate workup for an adult patient presenting with involuntary movements?

Workup of Involuntary Movements in Adults

Begin with a detailed clinical characterization of the movement disorder itself, as the diagnosis of involuntary movements is fundamentally clinical rather than laboratory-based, and the pattern of movement directly determines the diagnostic pathway and necessary investigations. 1, 2

Initial Clinical Assessment

Movement Characterization

The first critical step is to systematically describe the involuntary movement using three key parameters 1, 3:

• Temporal pattern/rhythmicity: Determine if movements are regular (tremor), mostly regular, irregular, or completely irregular (myoclonus) 1, 3
• Triggering conditions: Document whether movements occur at rest, with posture, during action, with emotional stress, or respond to sensory tricks 1, 3
• Movement pattern: Note stereotypy, muscle distribution, laterality, and whether features overlap between movement types 1, 3

A flexible diagnostic approach is essential because many involuntary movements show features of multiple categories or shift between different types, and forcing classification into rigid categories can lead to diagnostic errors. 1

Specific Movement Types and Their Implications

Chorea and ballismus are clinically and neuropharmacologically related, both responding to benzodiazepines and D2 receptor blockers 1. When chorea is the predominant feature, genetic testing for Huntington disease (HD) should be performed in concert with initial imaging, as imaging may be normal early in the disease course 4. HD genetic testing determines CAG repeat number (>38 repeats confirms diagnosis) and should include genetic counseling 4.

Dystonia is characterized by excessive muscle contraction in strength, spread, and duration, with recent evidence emphasizing sensorimotor cortex involvement in focal dystonia 1.

Paroxysmal kinesigenic dyskinesia (PKD) presents with attacks lasting <1 minute in >98% of patients, triggered by sudden voluntary movements, with peak frequency during puberty 4. PRRT2 genetic testing should be obtained as this accounts for the majority of PKD cases worldwide 4.

Essential Laboratory Investigations

Metabolic and Endocrine Screening

Measure pH-corrected ionized calcium levels (the most accurate method) along with albumin-corrected total calcium, as hypocalcemia can induce or worsen any type of movement disorder including dystonia, myoclonus, tremors, and parkinsonism-like symptoms. 5, 6 Hypocalcemia affects neurotransmission in the basal ganglia and increases neuronal excitability 5.

Additional critical laboratory tests include 5, 6:

• Parathyroid hormone (PTH) levels
• Magnesium levels (hypomagnesemia can cause or perpetuate hypocalcemia)
• Phosphate levels (to calculate calcium-phosphorus product)
• Thyroid function tests
• Renal function parameters (creatinine, BUN)

High-Risk Populations for Metabolic Causes

Patients with 22q11.2 deletion syndrome have 80% lifetime prevalence of hypocalcemia and associated movement disorders 5. Biological stressors (surgery, fracture, injury, childbirth, infection) increase hypocalcemia risk 5.

Neuroimaging Strategy

MRI Brain (Primary Modality)

MRI of the brain is the optimal imaging modality for evaluating involuntary movements, with diffusion-weighted imaging (DWI) and T2-FLAIR sequences being most sensitive. 4

Administer intravenous contrast routinely to identify autoimmune and inflammatory etiologies, which are important treatable causes of rapidly progressive movement disorders 4.

Specific MRI Findings by Condition

For rapidly progressive dementia with involuntary movements (suspected Creutzfeldt-Jakob disease):

• Look for T2 hyperintensity and diffusion restriction in cortex (frontal, temporal, parietal), basal ganglia (caudate, putamen), and thalami (pulvinar sign, hockey stick sign) 4
• Gray matter involvement with relative white matter sparing is characteristic 4

For Huntington disease:

• Early imaging may be normal; progressive disproportionate neostriatal volume loss appears later 4
• MRI is not the primary diagnostic test (genetic testing is), but helps exclude other etiologies 4

For ischemic causes:

• Small infarcts in frontal corona radiata (not extending to cortex or basal ganglia) can cause contralateral involuntary movements 7
• Ischemic dysfunction of frontal cortical and subcortical motor pathways is the suspected mechanism 7

CT Head (Limited Role)

CT has limited soft-tissue characterization compared to MRI and is not preferred 4. However, CT without contrast is appropriate for excluding acute cerebrovascular disease or infectious/inflammatory processes when MRI is unavailable or contraindicated 4.

Advanced Imaging (Selected Cases)

SPECT Brain Perfusion

Tc-99m HMPAO SPECT/CT demonstrates regional cerebral blood flow changes that may appear before MRI signal abnormalities in rapidly progressive disorders, but lack of specificity limits its utility as an initial study 4. Consider SPECT when MRI is normal but clinical suspicion for CJD remains high 4.

FDG-PET/CT

There is insufficient evidence to support routine use of FDG-PET/CT in the initial evaluation of chorea or suspected HD 4.

Neurophysiologic Studies

EMG with simultaneous recording from multiple muscles provides characteristic patterns for differential diagnosis and quantifies movement severity 8. Surface electrode recordings can distinguish:

• Tremor: Most rhythmic pattern
• Chorea and ballismus: Irregular patterns
• Dystonia: Excessive, prolonged muscle contraction patterns
• Myoclonus: Most irregular, can be positive (contraction) or negative (sudden cessation) 1, 8

Critical Pitfalls to Avoid

Do not attribute involuntary movements to a single obvious cause without excluding metabolic derangements, particularly hypocalcemia, which is reversible and can present with any movement disorder phenotype 5.

Do not delay genetic testing in suspected HD while waiting for imaging changes to develop, as early disease may show normal imaging 4.

Do not overlook medication-induced causes: Dyskinesia and akathisia are often drug-induced 1. Review all medications including antipsychotics, antiemetics, and calcium channel blockers.

Recognize that movement patterns may overlap or shift: Athetosis often overlaps with chorea and dystonia; some movements show features of multiple categories 1. Document all observed features rather than forcing a single classification.

Special Considerations for Rapidly Progressive Cases

When involuntary movements are part of a rapidly progressive dementia syndrome, MRI brain with contrast and DWI sequences should be obtained urgently 4. If MRI shows characteristic findings but remains equivocal, consider SPECT perfusion imaging 4.

For paroxysmal movements triggered by sudden actions with duration <1 minute, prioritize PRRT2 genetic testing over extensive neuroimaging, as this represents the most common genetic cause of PKD 4.