What is the appropriate work-up and treatment for an older adult presenting with a rest tremor, suspected to have Parkinson's disease?

Work-Up for Rest Tremor

A unilateral resting tremor should be immediately evaluated for Parkinson's disease (PD) as the primary diagnosis, as this is the hallmark feature of PD and typically begins asymmetrically. 1, 2

Clinical Evaluation

Key Diagnostic Features to Assess

Tremor Characteristics:

• Resting tremor occurs when the hand is fully supported against gravity and disappears with voluntary movement 1, 2
• Frequency of 4-6 Hz is typical for parkinsonian tremor 3, 4
• Asymmetric onset strongly suggests PD rather than other causes 2, 5

Essential Diagnostic Criteria for Parkinson's Disease:

• Diagnosis requires two of three major features: resting tremor, bradykinesia, and rigidity 5, 6
• Examine specifically for bradykinesia (slowness of movement) and cogwheel rigidity 5, 6
• Look for asymmetric presentation, as PD typically starts unilaterally 2, 6

Additional Clinical Signs:

• Prodromal features: REM sleep behavior disorder, hyposmia (reduced sense of smell), constipation 6
• Minor signs: cognitive slowing, speech abnormalities, depression, dysautonomia, sleep disturbances 5
• Postural instability (typically later in disease course) 1

Differential Diagnosis to Consider

Essential Tremor (if tremor is NOT at rest):

• Occurs primarily with posture or action, not at rest 2, 3
• Often involves head and voice in addition to hands 7
• Family history positive in approximately 50% of cases 2, 4

Functional/Conversion Tremor:

• Variable frequency, amplitude, and direction 2, 8
• Entrainable tremor (changes with voluntary rhythmic movements of other body parts) 2
• Sudden onset in context of stress or illness 2

Atypical Parkinsonism:

• Progressive supranuclear palsy (PSP): early falls, vertical gaze palsy, axial rigidity 1
• Multiple system atrophy (MSA): prominent autonomic dysfunction, cerebellar signs 1
• Corticobasal degeneration (CBD): asymmetric limb rigidity with "alien limb phenomenon," apraxia 1

Imaging Work-Up

MRI Brain:

• Obtain brain MRI if there is evidence of abnormal neurologic activity beyond typical PD features 1
• MRI helps exclude structural lesions (brainstem stroke, tumor, demyelinating disease) that can cause parkinsonian symptoms 1
• MRI findings can help differentiate atypical parkinsonism: PSP shows midbrain atrophy, MSA shows putaminal changes 1

Dopamine Transporter SPECT Imaging:

• Use DaTscan when the presence of parkinsonism is uncertain on clinical examination 6
• Improves diagnostic accuracy when distinguishing PD from essential tremor or functional tremor 6
• Not routinely needed when clinical diagnosis is clear 6

Medication Review

Critical to assess for drug-induced parkinsonism:

• Discontinue potentially causative drugs before starting tremor medications 2
• Common culprits: antipsychotics, metoclopramide, valproic acid, lithium 3
• Medications that can exacerbate tremor: SSRIs, TCAs, MAOIs, stimulants 1, 2

Treatment Approach

First-Line Pharmacologic Treatment for Parkinson's Disease

Levodopa-Carbidopa:

• Most effective symptomatic treatment for all parkinsonian motor symptoms including tremor 2, 9, 6
• Start at 25/100 mg three times daily, titrate based on response 2, 9
• Levodopa crosses the blood-brain barrier and is converted to dopamine, relieving PD symptoms 9
• Carbidopa reduces peripheral conversion, allowing lower levodopa doses and reducing nausea 9
• Plasma half-life increases from 50 minutes to 1.5 hours when combined with carbidopa 9

Alternative Pharmacologic Options

Dopamine Agonists (Second-Line):

• Pramipexole: start 0.375 mg/day, titrate to maximally tolerated dose up to 4.5 mg/day in divided doses 10
• Ropinirole: similar efficacy but requires careful monitoring for somnolence (up to 40% in PD patients) and syncope 11
• Important caveat: These agents have higher rates of impulse control disorders and somnolence compared to levodopa 11, 6

Anticholinergics:

• May decrease tremor but often cause mental side effects in elderly patients 4
• Use with extreme caution in older adults due to cognitive risks 4

Advanced Therapies for Refractory Cases

Deep Brain Stimulation (DBS):

• Consider when medical therapies fail at maximum tolerated doses 2, 8, 6
• Effective for medication-resistant tremor, "off periods," and dyskinesias 6

MRI-Guided Focused Ultrasound (MRgFUS) Thalamotomy:

• Effective for unilateral tremor causing significant functional impairment 2
• Less invasive alternative to DBS for selected patients 2

Treatment for Non-Parkinsonian Tremor

If Essential Tremor is Diagnosed:

• Propranolol is first-line pharmacologic treatment 8, 3, 4
• Primidone is alternative first-line option 3, 4
• Do not use propranolol for parkinsonian resting tremor—beta-blockers are only effective for essential tremor 2, 8

If Functional Tremor is Diagnosed:

• Non-pharmacological interventions are primary treatments: rhythm modification techniques, muscle relaxation, activity modification 2, 8
• Pharmacotherapy has no evidence of benefit for functional tremor 2
• Do not dismiss as "psychogenic"—symptoms are involuntary and require specific therapeutic approaches 2, 8

Common Pitfalls to Avoid

• Do not diagnose essential tremor based solely on unilateral resting tremor—essential tremor is primarily postural/action tremor 2, 3
• Do not assume all tremor in elderly patients is benign essential tremor—always assess for parkinsonian features 5, 4
• Do not start dopaminergic therapy without confirming clinical diagnosis of parkinsonism (two of three cardinal features) 5, 6
• Do not overlook atypical features suggesting Parkinson-plus syndromes (early falls, prominent autonomic dysfunction, poor levodopa response) 1, 6
• Do not use excessive adaptive equipment in functional tremor, as this may reinforce abnormal movement patterns 8