What are the potential causes and treatment options for a patient presenting with tremors?

Tremor Causes and Treatment

Primary Tremor Etiologies

Tremor is an involuntary rhythmic oscillation of body parts with distinct causes that must be differentiated by activation condition, topographic distribution, and frequency to guide appropriate treatment. 1

Most Common Tremor Types in Primary Care

• Essential tremor is the most common pathologic tremor (prevalence 0.4-6%), presenting as bilateral action tremor of arms and hands with 4-8 Hz frequency, often inherited in autosomal-dominant fashion 2, 3, 1
• Parkinsonian tremor occurs in >70% of Parkinson's disease patients, typically presenting as unilateral 4-6 Hz resting tremor that becomes less prominent with voluntary movement 3, 1
• Enhanced physiologic tremor affects all persons as low-amplitude, high-frequency tremor that becomes symptomatic when enhanced by anxiety, medications, caffeine, or fatigue 1

Neurological Causes

• Cerebellar pathology produces intentional tremor characterized by coarse, irregular tremor that becomes more pronounced during goal-directed movements with "wing-beating" appearance, often accompanied by dysarthria and ataxic gait 4
• Multiple sclerosis causes intentional tremor through demyelinating lesions in cerebellar pathways 4
• Wilson's disease presents with characteristic "pseudosclerosis dominated by tremor" as part of its neurological manifestations 4
• Traumatic brain injury affecting cerebellum or its connections can lead to intentional tremor 4
• Peripheral neuropathy can manifest with tremor 3

Drug and Metabolic Causes

• Medication-induced tremor should always be considered in recent-onset tremor, including certain medications that can cause or exacerbate intentional tremor 4, 1
• Alcohol withdrawal produces characteristic tremor that may respond to propranolol 3, 5
• Toxic exposures affecting cerebellar function can contribute to intentional tremor 4
• Metabolic disturbances should be evaluated in patients with recent-onset tremor 1

Other Causes

• Dystonic tremor presents as irregular, position-specific tremor 4
• Functional (psychogenic) tremor features abrupt onset, spontaneous remission, changing characteristics, and extinction with distraction 1
• Orthostatic tremor may respond to clonazepam 5

Treatment Approach

Essential Tremor Treatment

The American Academy of Neurology recommends first-line pharmacological treatment with propranolol (80-240 mg/day) or primidone, initiated only when tremor interferes with function or quality of life. 2

• Propranolol is the only FDA-approved medication for essential tremor and can provide dual benefits for patients with hypertension, but should be avoided in chronic obstructive pulmonary disease, bradycardia, or congestive heart failure 2, 6
• Primidone is equally effective as first-line therapy and can be combined with propranolol if monotherapy provides inadequate control 6, 3
• Alternative beta-blockers (atenolol, metoprolol) can occasionally be used if propranolol causes adverse effects 6
• Benzodiazepines (clonazepam) may provide benefit when primidone and propranolol fail 6, 3
• Second-line agents include gabapentin and topiramate for medication-refractory cases 6
• Botulinum toxin injections into neck muscles can provide relief for disabling head or voice tremor, though hand injections cause bothersome weakness and are not widely used 6, 7

Surgical Options for Refractory Essential Tremor

MRI-guided focused ultrasound (MRgFUS) thalamotomy targeting the VIM nucleus provides sustained tremor improvement of 56% at 2-4 years with lower complication rate (4.4%) compared to radiofrequency thalamotomy (11.8%) and deep brain stimulation (21.1%). 2

• MRgFUS contraindications include inability to undergo MRI, skull density ratio <0.40, need for bilateral treatment, or previous contralateral thalamotomy 2
• Deep brain stimulation (DBS) of the thalamus has been FDA-approved since 1997 and provides adequate tremor control in approximately 90% of patients, with fewer complications than bilateral ablative procedures 6, 7, 5
• Thalamotomy and DBS have comparable efficacy, but DBS is preferred for bilateral procedures to avoid adverse effects of bilateral ablation 6

Parkinsonian Tremor Treatment

• Carbidopa-levodopa combination remains first-line treatment for parkinsonian tremor 3, 5
• Anticholinergics can also be effective for Parkinson's disease tremor 3

Intentional Tremor Treatment

Intentional tremor is more challenging to treat pharmacologically than essential tremor, but physical therapy and occupational therapy with adaptive devices may help improve function. 2

• Isoniazid may control cerebellar tremor associated with multiple sclerosis 5
• Rehabilitation strategies for functional tremor include superimposing alternative voluntary rhythms, using the unaffected limb to entrain tremor to stillness, muscle relaxation to prevent cocontraction, and using gross rather than fine movements 8

Important Caveats

• Potency units of botulinum toxin products are not interchangeable between different preparations 9
• Spread of toxin effects can cause swallowing and breathing difficulties that may be life-threatening; seek immediate medical attention if respiratory, speech, or swallowing difficulties occur 9
• Concomitant neuromuscular disorders may exacerbate clinical effects of treatment 9
• Aminoglycosides, curare-like agents, and muscle relaxants can potentiate botulinum toxin effects and require close observation 9