In a 44-year-old man with three months of bradykinesia, rigidity and tremor, what reversible or secondary causes of early-onset parkinsonism must be excluded, and what is dopamine transporter single-photon emission computed tomography (DAT‑SPECT) imaging?

Early-Onset Parkinsonism: Secondary Causes to Exclude and DAT-SPECT Imaging

Secondary and Reversible Causes That Must Be Excluded

In a 44-year-old man presenting with parkinsonism, you must systematically exclude drug-induced parkinsonism, Wilson's disease, structural brain lesions, vascular disease, and metabolic disorders before diagnosing idiopathic Parkinson's disease. 1, 2

Drug-Induced Parkinsonism

• Obtain a detailed medication history focusing on dopamine-blocking agents including antipsychotics (typical and atypical), antiemetics (metoclopramide, prochlorperazine), and calcium channel blockers 2, 3
• Drug-induced parkinsonism can be treated with anticholinergic or mild dopaminergic agents such as amantadine 2
• This is a critical exclusion because it is completely reversible with medication discontinuation 4

Wilson's Disease (Critical in Young-Onset Cases)

• Wilson's disease is essential to exclude in any patient under 50 years with parkinsonism 1
• Order serum ceruloplasmin levels, 24-hour urinary copper excretion, and slit-lamp examination for Kayser-Fleischer rings 1
• Brain MRI may show characteristic "face of the giant panda" sign or hyperintensities in basal ganglia, thalamus, and brainstem that are virtually pathognomonic 1
• Neurologic Wilson's disease manifests with Parkinsonian characteristics including dystonia, hypertonia, rigidity, and tremors 1

Structural and Vascular Causes

• MRI brain without contrast is mandatory to exclude structural lesions, vascular disease, hydrocephalus, or focal pathology 1, 2, 5
• Look for evidence of multiple lacunar infarcts, white matter disease, or focal lesions that could cause vascular parkinsonism 1, 4
• MRI is often normal in early idiopathic PD but essential to rule out alternative diagnoses 2, 5

Metabolic Disorders

• Assess thyroid function (T3/FT3, T4/FT4, TSH) to exclude hyperthyroidism 1
• Evaluate calcium-phosphorus metabolism (serum calcium, phosphorus, parathyroid hormone) and perform brain CT to assess for intracranial calcification 1
• Check blood glucose to exclude glucose metabolism disorders 1
• Test bilirubin levels to screen for kernicterus history 1

Red Flags Suggesting Secondary Causes

• Age of onset over 20 years (though your patient is 44, early onset still warrants thorough workup) 1
• Early severe autonomic dysfunction, cerebellar signs, or pyramidal signs suggest Multiple System Atrophy rather than idiopathic PD 1, 5, 3
• Vertical gaze palsy (especially downward) suggests Progressive Supranuclear Palsy 1, 2, 5
• Asymmetric rigidity with alien hand phenomenon suggests Corticobasal Syndrome 1, 2, 5

---

What is Dopamine Transporter SPECT Imaging (DAT-SPECT)

Dopamine transporter SPECT imaging (using I-123 ioflupane, also called DaTscan) is a nuclear medicine study that visualizes presynaptic dopamine terminals in the striatum to differentiate true dopamine-deficient parkinsonian syndromes from conditions that mimic parkinsonism but have intact dopaminergic function. 1, 6, 7

How DAT-SPECT Works

• I-123 ioflupane binds to dopamine transporters on presynaptic dopaminergic neurons in the striatum 1, 6, 8
• The radiotracer demonstrates the integrity of the nigrostriatal dopaminergic pathway 6, 8
• In parkinsonian syndromes with dopaminergic neuronal loss (PD, MSA, PSP, CBD), there is decreased radiotracer uptake in the striatum, typically progressing from posterior to anterior (putamen to caudate) 1, 8, 4

Clinical Utility in Your Patient

• DAT-SPECT is valuable when the clinical diagnosis is uncertain and helps differentiate true parkinsonian syndromes from essential tremor, drug-induced tremor, psychogenic parkinsonism, and dystonic tremors 1, 6, 7, 8
• A normal DAT-SPECT essentially excludes dopamine-deficient parkinsonian syndromes and identifies "subjects without evidence of dopamine deficiency" (SWEDDs) 1, 2, 8
• The scan demonstrates abnormality early in the disease course, even in presymptomatic or prodromal stages, before structural imaging shows changes 6, 8, 4
• It can detect subclinical dopaminergic dysfunction in at-risk subjects 8, 4

Interpretation Patterns

• Idiopathic PD: Asymmetric decreased uptake, typically more pronounced in putamen contralateral to the more affected side 8, 4
• Atypical parkinsonian syndromes (MSA, PSP, CBD): Also show abnormal DAT-SPECT with decreased striatal uptake, though patterns may differ slightly 8, 4
• Essential tremor, drug-induced parkinsonism, psychogenic parkinsonism: Normal DAT-SPECT 8, 4

Important Limitations

• DAT-SPECT cannot distinguish between different types of neurodegenerative parkinsonian disorders (PD vs. MSA vs. PSP vs. CBD) since all show dopaminergic deficiency 8, 4
• Reduced striatal DAT availability should be regarded as supportive rather than diagnostic of dopamine-deficient parkinsonism 8
• Clinical correlation is essential for proper interpretation 6, 7

Recommended Imaging Algorithm for Your Patient

1. First: Obtain MRI brain without contrast to exclude structural, vascular, or other secondary causes 1, 2, 5
2. Second: Consider DAT-SPECT if clinical diagnosis remains uncertain after history, examination, and MRI 1, 2, 6
3. Do not order amyloid PET/CT or tau PET/CT, as there is no evidence supporting their use in parkinsonian syndrome evaluation 2

Common Pitfalls to Avoid

• Never skip structural imaging (MRI) before ordering functional imaging like DAT-SPECT 2
• Do not rely solely on DAT-SPECT for diagnosis; it must be interpreted in clinical context by a neurologist or movement disorder specialist 2, 5
• Remember that normal DAT-SPECT excludes parkinsonian syndromes, which is extremely valuable for avoiding unnecessary dopaminergic therapy 1, 2, 8
• Be aware that certain medications can interfere with DAT-SPECT results, so review the patient's medication list before ordering 6