What is the appropriate work‑up for a patient with suspected parkinsonism?

Work-Up of Parkinsonism

Begin with a focused clinical assessment for bradykinesia plus at least one cardinal sign (resting tremor, rigidity, or postural instability), then obtain brain MRI without contrast to exclude structural causes, followed by I-123 ioflupane SPECT/CT (DaTscan) if the diagnosis remains uncertain after clinical evaluation. 1

Step 1: Clinical Assessment for Cardinal Motor Features

Bradykinesia is the essential diagnostic feature and must be present. 1 Look for:

• Slowness affecting voluntary movements including fine motor tasks (buttoning clothes, writing), gross motor activities (walking, turning), facial expressions, and speech 1
• At least one additional cardinal sign: resting tremor, rigidity, or both 1
• Rigidity assessment technique: Passively move the patient's limbs while instructing complete relaxation, assess resistance throughout the full range of motion, and note any cogwheel phenomenon (ratchet-like resistance when rigidity combines with tremor) 1
• Enhancement maneuver: Ask the patient to perform an activation task with the contralateral limb (e.g., opening/closing the opposite hand) while testing for rigidity, as this brings out subtle rigidity that might otherwise be missed 1

Step 2: Screen for Red Flags Suggesting Atypical Parkinsonism

Certain clinical features indicate diagnoses other than idiopathic Parkinson's disease and require different management:

• Early severe autonomic dysfunction, cerebellar signs, or pyramidal signs suggest Multiple System Atrophy 1
• Vertical gaze palsy, especially downward suggests Progressive Supranuclear Palsy 1
• Asymmetric rigidity with alien hand phenomenon suggests Corticobasal Syndrome 1
• Ataxia is a red flag for non-PD parkinsonism 1

Step 3: Exclude Secondary and Reversible Causes

Drug-Induced Parkinsonism

• Review all medications for dopamine-blocking agents (antipsychotics, antiemetics) that can cause reversible parkinsonism 1
• Drug-induced parkinsonism typically shows a normal DaTscan, helping distinguish it from neurodegenerative causes 1, 2

Wilson's Disease (Mandatory in Patients < 50 Years)

• Measure serum ceruloplasmin 1
• 24-hour urinary copper excretion 1
• Slit-lamp examination for Kayser-Fleischer rings 1
• Brain MRI may reveal the "face of the giant panda" sign or hyperintensities in basal ganglia, thalamus, and brainstem 1

Metabolic and Endocrine Screening

• Thyroid function tests (TSH, free T4) to exclude hyperthyroidism 1
• Serum calcium and phosphorus with non-contrast brain CT to detect intracranial calcifications 1
• Blood glucose to exclude diabetes-related movement abnormalities 1
• Serum bilirubin to identify remote history of kernicterus 1

Step 4: Structural Imaging—MRI Brain Without Contrast (First-Line)

MRI brain without contrast is mandatory before any functional imaging. 1, 2

• Superior soft-tissue characterization and sensitivity to iron deposition make MRI the optimal structural imaging modality 1, 2
• Rules out structural lesions, vascular disease, hydrocephalus, or focal abnormalities that could explain parkinsonism 1
• MRI is often normal in early PD but essential to exclude alternative diagnoses 1
• Specific findings to assess: multiple lacunar infarcts, diffuse white-matter disease, or focal basal ganglia lesions suggesting vascular parkinsonism 1

Common pitfall: Skipping structural imaging and proceeding directly to functional imaging misses treatable structural causes. 3

Step 5: Functional Imaging—I-123 Ioflupane SPECT/CT (DaTscan) When Diagnosis Is Uncertain

Use DaTscan when clinical presentation is unclear after history, examination, and MRI. 1, 2

Indications

• Differentiates true Parkinsonian syndromes from essential tremor or drug-induced tremor 1, 2
• Valuable when clinical diagnosis remains uncertain after initial assessment 1

Interpretation

• Abnormal scan (decreased striatal uptake): Confirms dopaminergic neuronal loss, consistent with neurodegenerative parkinsonism (PD, MSA, PSP, CBD) 1, 2
• Pattern of abnormality: Decreased radiotracer uptake progresses from posterior putamen to anterior caudate 1
• Normal scan: Essentially excludes Parkinsonian syndromes and identifies "subjects without evidence of dopamine deficiency" (SWEDDs) 1, 2
• Drug-induced parkinsonism typically yields a normal DaTscan, helping separate medication-related symptoms from true nigrostriatal degeneration 1

Critical Limitations

• DaTscan cannot differentiate among specific Parkinsonian syndromes (PD vs. MSA vs. PSP vs. CBD); all show abnormal dopaminergic depletion 1
• Findings must be interpreted in clinical context by a neurologist or movement disorder specialist 1

Step 6: Optional Advanced Imaging—FDG-PET/CT for Atypical Parkinsonism

FDG-PET/CT has limited utility for initial evaluation but can help differentiate PSP from idiopathic PD. 1, 2

• Characteristic PSP pattern: Hypometabolism in medial frontal and anterior cingulate cortices, striatum, and midbrain 1, 2
• Very limited good-quality evidence supports its use for initial Parkinsonian syndrome evaluation 1

Step 7: Specialist Referral for Diagnostic Confirmation

General neurologists or movement disorder specialists should confirm the diagnosis because correctly diagnosing parkinsonian syndromes on clinical features alone is challenging. 1, 3

When to Refer

• Atypical presentation 3
• Rapidly progressive symptoms 3
• Early onset 3
• Poor response to dopaminergic medications 3
• Presence of neurological signs not typical for PD 3

Why Specialist Involvement Matters

• Misdiagnosis leads to inappropriate treatment and missed opportunities for effective intervention 3
• Missing atypical parkinsonian syndromes (PSP, MSA, CBD) results in incorrect prognosis and ineffective treatment strategies 3
• Imaging studies require proper interpretation in clinical context, another reason for neurologist involvement 1

Imaging Modalities to Avoid

• Do NOT order amyloid PET/CT—no relevant literature supports its use in Parkinsonian syndrome evaluation 1
• Do NOT order tau PET/CT for initial Parkinsonian syndrome workup 1
• CT head is not preferred due to limited soft-tissue characterization compared to MRI, though it can demonstrate patterns of regional volume loss in atypical parkinsonism 2

Assessment Tools for Disease Severity

Once diagnosis is established:

• Unified Parkinson's Disease Rating Scale (UPDRS) is the standard clinical assessment tool, consisting of four parts: mentation, activities of daily living, motor examination, and complications of therapy 1
• Movement Disorder Society-UPDRS (MDS-UPDRS) is a newer version with improved evaluation of non-motor aspects, freezing of gait, and tremor subtypes 1
• Regular monitoring of nutritional and functional status throughout the disease course is essential, including body weight, vitamin status, dysphagia screening, and nutritional risk assessment 1

Common Pitfalls to Avoid

• Failure to have the patient completely relax during rigidity testing leads to false positives from voluntary muscle contraction 1
• Not using activation maneuvers may cause you to miss subtle rigidity 1
• Confusing spasticity (velocity-dependent resistance) with rigidity (constant resistance throughout movement) 1
• Relying solely on clinical diagnosis without confirmatory testing in atypical cases leads to diagnostic uncertainty and delayed appropriate management 3