What are the differential diagnoses for tremor?

Differential Diagnoses for Tremor

Systematic Classification by Activation Pattern

The first critical step is to characterize the tremor by its activation condition—resting, postural/action, or intention—as this immediately narrows the differential diagnosis and identifies life-threatening conditions that must be excluded. 1, 2

Resting Tremor (4-6 Hz, improves with movement)

• Parkinson's disease is the most common cause of resting tremor, typically presenting unilaterally and becoming less prominent with voluntary movement 1, 3
• Drug-induced parkinsonism from antipsychotic medications and dopamine antagonists can precipitate resting tremor with lead-pipe rigidity 2
• Neuroleptic malignant syndrome must be presumed in patients on antipsychotics presenting with resting tremor, severe rigidity, autonomic instability, and fever until proven otherwise 2
• Atypical parkinsonian syndromes including multiple system atrophy and progressive supranuclear palsy should be considered when red flags are present: early prominent falls, rapid progression, poor levodopa response, early autonomic dysfunction, or vertical gaze palsy 1

Postural/Action Tremor (occurs with voluntary muscle contraction)

• Essential tremor is the most common pathological tremor, affecting 0.4-6% of the population, transmitted in autosomal-dominant fashion in 50% of cases 3
• Enhanced physiologic tremor is low-amplitude, high-frequency tremor exacerbated by anxiety, caffeine, fatigue, or medications 3
• Drug-induced tremor from medications including lithium (fine hand tremor, muscle hyperirritability, fasciculations) 4 and valproic acid (tremor in 25-57% of patients depending on dose) 5
• Hyperthyroidism and other metabolic derangements (hypoglycemia, electrolyte abnormalities) must be investigated with thyroid function, glucose, and electrolyte panels 2
• Dystonic tremor occurs in the context of dystonia and may be position-specific 6, 3
• Orthostatic tremor is a rare syndrome with high-frequency tremor (13-18 Hz) occurring specifically when standing 7, 6

Intention Tremor (worsens as target is approached)

• Cerebellar pathology from stroke, multiple sclerosis, or structural lesions presents with intention tremor accompanied by dysmetria, dysdiadochokinesia, and ataxia 2, 6
• Holmes' tremor (previously called rubral tremor) is characterized by low frequency and the presence of both resting and intention components 7

Critical Life-Threatening Diagnoses Not to Miss

Wilson's Disease in Young Patients

In any young patient presenting with tremor, Wilson's disease is the critical diagnosis that must be excluded, as it is treatable and can present with tremor, dystonia, and parkinsonian features. 1

• Check serum ceruloplasmin and 24-hour urinary copper 1
• Perform slit-lamp examination for Kayser-Fleischer rings 1
• Look for characteristic features: drooling and oropharyngeal dystonia 1

Serotonin Syndrome

• Serotonin syndrome from serotonergic medications presents with tremor as a hallmark feature, accompanied by hyperreflexia, clonus, and autonomic hyperactivity, requiring prompt recognition 2

Additional Tremor Syndromes

Functional (Psychogenic) Tremor

• Highly variable tremor that stops completely with distraction is the hallmark of functional tremor 1
• Additional features include abrupt onset, spontaneous remission, changing tremor characteristics, and extinction with distraction 3

Task-Specific Tremors

• Primary writing tremor and other task-specific tremors occur only during specific activities 6
• Voice tremor involves abnormal laryngeal motor neuron firing patterns 8

Diagnostic Evaluation Algorithm

Step 1: Document Tremor Characteristics

• Topographic distribution (which body parts are affected) 1
• Frequency (low <4 Hz, medium 4-8 Hz, high >8 Hz) 1
• Factors that worsen or improve the tremor 1

Step 2: Focused Neurological Examination

• Assess for bradykinesia, rigidity, and postural instability to identify parkinsonian features 1
• Evaluate gait pattern for shuffling, festination, or freezing 1
• Test for cerebellar signs: dysmetria, dysdiadochokinesia, ataxia 2
• Look for dystonia, peripheral neuropathy, and other associated neurological signs 2

Step 3: Medication and Substance Review

• Perform thorough medication review for recent additions or dose changes 2
• Assess caffeine intake, which is extremely common in young patients 1
• Do not confuse akathisia (severe restlessness from antipsychotics manifesting as pacing) with tremor 1

Step 4: Laboratory Evaluation

• Thyroid function tests 2
• Blood glucose and electrolyte panels 2
• In young patients: serum ceruloplasmin and 24-hour urinary copper for Wilson's disease 1

Step 5: Neuroimaging

• MRI brain without contrast is the optimal imaging modality to evaluate for structural causes, parkinsonian syndromes, cerebellar pathology, and Wilson disease 1
• Consider DaTscan (ioflupane SPECT) to visualize dopaminergic pathway integrity if diagnostic uncertainty exists between parkinsonian syndromes versus essential tremor or drug-induced tremor; a normal scan essentially excludes parkinsonian syndromes 1

Step 6: Therapeutic Trial

• A therapeutic trial of levodopa/carbidopa can help differentiate Parkinson's disease from atypical parkinsonism 1

Critical Pitfalls to Avoid

• Do not assume all tremors are benign essential tremor—Wilson's disease must be excluded in young patients 1
• Do not overlook medication and substance-induced tremor, including caffeine 1
• Do not miss neuroleptic malignant syndrome in patients on antipsychotics with tremor, rigidity, and fever 2
• Do not confuse akathisia with tremor 1
• In patients with suspected cerebellar tremor, ensure MRI is performed to identify structural lesions or demyelinating disease 1