What is the differential diagnosis (ddx) and management of tremor in an adult patient with no significant past medical history?

Differential Diagnosis and Management of Tremor

Initial Diagnostic Approach: Classify by Activation Pattern

The first critical step is to determine when the tremor occurs: at rest, with posture, or during movement—this single observation narrows your differential dramatically. 1

Rest Tremor (4-6 Hz)

• Parkinson's disease is the primary diagnosis when tremor occurs at rest and improves with voluntary movement 1, 2
• Classic "pill-rolling" quality affecting hands and legs 1
• Typically unilateral at onset in over 70% of cases 2
• Associated with bradykinesia, rigidity, and postural instability 3

Action Tremor (Postural/Kinetic)

• Essential tremor is the most common pathologic tremor (0.4-6% prevalence), presenting as bilateral postural and kinetic tremor at 4-8 Hz 3, 2
• Autosomal dominant inheritance in 50% of cases 2
• Primarily affects upper extremities and head 3
• Enhanced physiologic tremor appears with anxiety, caffeine, fatigue, or medications 2
• Low-amplitude, high-frequency tremor that all persons have but becomes symptomatic under stress 2

Intention Tremor (Worsens During Goal-Directed Movement)

• Cerebellar pathology produces coarse, irregular "wing-beating" tremor during finger-to-nose testing 4, 1
• Associated with dysarthria and ataxic gait 4, 5
• Caused by multiple sclerosis, traumatic brain injury, or structural cerebellar lesions 4, 5
• Does not stop with distraction, distinguishing it from functional tremor 1

Life-Threatening Causes to Exclude Immediately

Hepatic Encephalopathy

• Asterixis ("flapping tremor") is a negative myoclonus, not a true tremor, requiring emergency intervention 5
• Look for altered consciousness, jaundice, ascites, spider angiomata 5
• Check liver function tests and ammonia level urgently 5

Wilson's Disease

• Presents with "pseudosclerosis dominated by tremor" in young patients 4, 3
• Screen with ceruloplasmin, 24-hour urinary copper, and slit-lamp examination for Kayser-Fleischer rings 3

Drug-Induced Tremor

• Sympathomimetics (cocaine, amphetamines, decongestants) cause fine tremor with tachycardia and sweating 6
• Antipsychotics, lithium, valproate, and SSRIs are common culprits 1
• Urinary drug screen for illicit substances 6

Metabolic Disorders

• Hyperthyroidism causes fine tremor of outstretched hands with warm, moist skin, heat intolerance, and weight loss 6
• Screen with TSH and free T4 6
• Hypoglycemia and hypercalcemia also cause tremor 1

Functional (Psychogenic) Tremor

Distractibility is the key diagnostic feature—tremor stops when attention is redirected to another task 1

• Abrupt onset, spontaneous remission, and changing characteristics 2
• Variable frequency and amplitude 5

Management Algorithm

For Parkinson's Disease Tremor

• Anticholinergics (benztropine, trihexyphenidyl) for tremor-dominant disease 3
• Carbidopa-levodopa combination for comprehensive symptom control 3

For Essential Tremor

• First-line: Propranolol (beta-blocker) 3, 7
• Second-line: Primidone 3, 7
• Third-line: Topiramate 7
• Benzodiazepines for situational use 3
• Botulinum toxin for selected cases (head, voice tremor) 7

For Severe, Refractory Tremor

• Deep brain stimulation (DBS) of thalamic/subthalamic region is the current standard 7
• Provides significant improvement in tremor and quality of life 7
• Focused ultrasound thalamotomy is an emerging alternative 7
• Stereotactic thalamotomy as last resort 3

For Cerebellar Tremor

• Treat underlying cause (multiple sclerosis, structural lesions) 3
• Brain MRI essential to exclude brainstem tumors, demyelination, or stroke 5
• Symptomatic treatment often unsatisfactory 3

Critical Diagnostic Pitfalls

• Do not miss hepatic encephalopathy—asterixis requires immediate intervention, not outpatient workup 5
• Always check medication list—drug-induced tremor is common and reversible 6, 1
• Test distractibility—functional tremor wastes resources if not identified early 1, 2
• Young patients with tremor warrant Wilson's disease screening—this is treatable if caught early 4, 3
• Unilateral rest tremor strongly suggests Parkinson's disease, not essential tremor 2