Laboratory and Diagnostic Testing for Movement Disorders
For patients presenting with movement disorders, obtain serum ceruloplasmin, 24-hour urinary copper, and slit-lamp examination for Kayser-Fleischer rings to exclude Wilson's disease in all patients under age 40, as this is a treatable cause that must not be missed. 1
Essential First-Line Laboratory Tests
Mandatory Screening Panel
- Serum ceruloplasmin: Values <0.1 g/L combined with Kayser-Fleischer rings establish Wilson's disease diagnosis 1
- 24-hour urinary copper: Levels >1.6 μmol/24h suggest Wilson's disease 1
- Complete blood count with peripheral smear: Essential to identify neuroacanthocytosis in young patients with chorea or other hyperkinetic movements 2
- Comprehensive metabolic panel: Includes glucose, renal function, liver function, and electrolytes to identify metabolic causes 1
- Thyroid function tests (TSH, free T4): Thyroid dysfunction can cause tremor and other movement abnormalities 1
Age-Specific Considerations
In children and young adults (<40 years), Wilson's disease exclusion is mandatory regardless of movement disorder phenotype, as delayed diagnosis leads to irreversible neurological damage and death 1, 2. The combination of low ceruloplasmin and Kayser-Fleischer rings is typically diagnostic, but ceruloplasmin can be falsely normal during acute inflammation or with estrogen use 1.
In adults presenting with parkinsonism, focus on excluding secondary causes through metabolic screening rather than extensive genetic testing for typical presentations 2, 3.
Secondary Laboratory Investigations Based on Clinical Features
For Acute-Onset Movement Disorders
- Serum and CSF autoimmune encephalitis panel: Including anti-NMDAR antibodies when psychotic features or seizures accompany movement disorder 1
- Infectious workup: HSV-1/2 PCR, VZV PCR, enterovirus PCR in CSF when encephalitis suspected 1
- Toxicology screen: For drug-induced movement disorders 4
- Paraneoplastic antibody panel: When subacute onset with systemic symptoms 1, 4
For Specific Movement Disorder Phenotypes
Chorea:
- Acanthocyte examination on peripheral smear (neuroacanthocytosis) 2
- Huntington's disease genetic testing if family history present 3
- Antiphospholipid antibodies and lupus serologies 4
Dystonia with systemic features:
- Serum calcium, magnesium, and parathyroid hormone (hypoparathyroidism can cause dystonia) 1
- Vitamin E levels (abetalipoproteinemia) 4
Parkinsonism in young adults:
- Serum ceruloplasmin and 24-hour urinary copper (Wilson's disease) 1, 2
- Consider genetic testing for early-onset Parkinson's genes (PRKN, PINK1, DJ-1) only after Wilson's disease excluded 5
Myoclonus:
- Serum B12 with methylmalonic acid and homocysteine (B12 deficiency causes elevated methylmalonic acid in 98.4% of cases) 1
- Celiac antibodies 4
- CSF 14-3-3 protein and MRI for Creutzfeldt-Jakob disease if rapidly progressive 1
Cerebrospinal Fluid Analysis
Obtain CSF when:
- Acute or subacute onset with fever or encephalopathy 1
- Suspected autoimmune or paraneoplastic etiology 1
- Atypical features suggesting inflammatory process 1
CSF studies should include:
- Cell count with differential, protein, glucose 1
- Oligoclonal bands and IgG index 1
- Autoimmune encephalitis antibodies 1
- Infectious PCR panels as clinically indicated 1
Genetic Testing Strategy
Genetic testing is NOT first-line for most movement disorders, as diagnosis remains primarily clinical 2, 3. Consider genetic testing only when:
- Family history of similar disorder is present 5, 3
- Onset before age 40 with atypical features 5
- Wilson's disease has been excluded in young patients 1, 2
For familial ALS, test for C9orf72, SOD1, FUS, and TARDBP genes 5.
Critical Pitfalls to Avoid
Do not miss Wilson's disease: Ceruloplasmin can be falsely normal during inflammation or with estrogen therapy, requiring repeat testing or proceeding directly to 24-hour urinary copper and slit-lamp examination 1. Even heterozygous carriers may have low ceruloplasmin without disease 1.
Do not rely on B12 levels alone: Serum B12 in the low-normal range (200-500 pg/dL) misses 44% of B12 deficiency cases; always add methylmalonic acid and homocysteine 1. Methylmalonic acid is more specific than homocysteine, which can be elevated in folate deficiency 1.
Do not order extensive autoimmune panels without clinical context: Autoimmune testing should be guided by acute/subacute onset, encephalopathy, seizures, or psychiatric features 1. Indiscriminate testing leads to false positives.
Hypocalcemia screening is essential in patients with known or suspected 22q11.2 deletion syndrome, as hypocalcemia can induce or worsen movement disorders and seizures 1. Check calcium, parathyroid hormone, and magnesium regularly 1.