What are the likely causes of tremors in a patient with a normal Magnetic Resonance Imaging (MRI) scan?

Causes of Tremors with Normal MRI

When MRI is normal, tremors are most commonly due to essential tremor, enhanced physiological tremor, or functional/psychogenic tremor—structural brain lesions are effectively excluded. 1

Primary Diagnostic Considerations

Essential Tremor

• Essential tremor is the most likely diagnosis when MRI is normal, characterized by bilateral action tremor of the arms and hands present for at least 3 years, with frequency of 4-8 Hz 1
• Affects hands in 90% of patients, head in 50%, voice in 30%, and legs/chin in 15% 2
• Positive family history reported in more than 60% of cases 2
• Alcohol ingestion decreases tremor in 74% of patients who are aware of this effect 2
• Normal MRI effectively excludes structural lesions, atrophy, or vascular disease that might suggest alternative diagnoses 1

Enhanced Physiological Tremor

• One of the most common causes of action tremor alongside essential tremor 3
• Exacerbated by emotional stress, caffeine consumption, and physical exertion 1
• Typically has higher frequency (8-12 Hz) than essential tremor 3

Functional/Psychogenic Tremor

• Not a diagnosis of exclusion—requires demonstration of specific clinical signs including variability in tremor characteristics, distractibility, entrainment with voluntary movements, and sudden onset 3
• Normal neuroimaging supports this diagnosis when clinical features are present 3

Parkinsonian Syndromes

Parkinson's Disease

• Most common cause of rest tremor (4-6 Hz affecting arms and legs) 4
• Normal MRI does not exclude Parkinson's disease, as it is a clinical diagnosis 5
• Ioflupane SPECT/CT can essentially exclude Parkinsonian syndromes by demonstrating normal dopamine transporter uptake in the striatum 1
• Coexists with essential tremor in 6.1% of cases—more frequent than expected in the general population 2

Other Neurological Causes with Normal MRI

Dystonic Tremor

• Isolated head tremor is more likely dystonic rather than essential tremor 3
• Coexisting dystonia found in 6.9% of essential tremor patients 2
• Responds to botulinum toxin injections as treatment of choice 3

Task-Specific Tremors

• Primary writing tremor and other focal tremors can occur with normal structural imaging 6
• Requires specific clinical examination during the triggering task 6

Orthostatic Tremor

• Rare form presenting with tremor specifically when standing 6
• Normal brain MRI expected, as this is a functional disorder of postural control 6

Metabolic and Toxic Causes

Wilson's Disease

• Should not be missed as it is treatable 6
• Can present with tremor and normal initial MRI, though copper deposition may eventually become visible 6
• Requires specific laboratory testing (ceruloplasmin, 24-hour urinary copper) rather than relying on imaging 6

Drug-Induced Tremor

• Medications can cause tremor without structural brain changes 4
• Common culprits include valproate, lithium, beta-agonists, and stimulants 3

Critical Diagnostic Algorithm

Step 1: Characterize tremor type

• Rest tremor → Consider Parkinson's disease, obtain ioflupane SPECT/CT if diagnosis uncertain 1
• Action tremor (postural/kinetic) → Essential tremor most likely 1
• Task-specific → Consider dystonic or focal tremor 3

Step 2: Assess duration and progression

• Duration ≥3 years supports essential tremor diagnosis 1
• Sudden onset or duration <1 year raises concern for functional tremor or secondary causes 1

Step 3: Evaluate for red flags requiring additional workup

• Age of onset >20 years without family history 1
• Rapid progression 1
• Associated neurological signs (ataxia, dystonia, parkinsonism) 6

Step 4: Consider functional imaging if diagnosis remains uncertain

• Ioflupane SPECT/CT to exclude Parkinsonian syndromes 1
• This is particularly useful when clinical examination is equivocal 5

Common Pitfalls to Avoid

• Do not assume normal MRI excludes all neurological causes—Parkinson's disease, essential tremor, and many other movement disorders have normal structural imaging 1
• Do not diagnose psychogenic tremor by exclusion alone—positive clinical signs must be demonstrated 3
• Do not overlook Wilson's disease in younger patients—requires specific metabolic testing, not imaging 6
• Do not miss medication-induced tremor—always review complete medication list including over-the-counter drugs and supplements 3

Treatment Implications

• For essential tremor, initiate treatment only when tremor interferes with function or quality of life 1
• First-line options: propranolol (80-240 mg/day) or primidone, effective in up to 70% of patients 1
• Propranolol contraindicated in chronic obstructive pulmonary disease, bradycardia, or congestive heart failure 1
• For refractory cases, surgical options include MRgFUS thalamotomy (56% sustained improvement at 4 years, 4.4% complication rate) or deep brain stimulation 1