Causes of Tremulousness

Tremulousness—an involuntary rhythmic shaking—arises from a broad spectrum of etiologies that can be systematically categorized by activation condition, medication exposure, metabolic derangements, and underlying neurologic or psychiatric disease.

Medication-Induced Tremor

Drug-induced tremor is one of the most common and reversible causes of tremulousness in clinical practice.

Antipsychotic medications produce extrapyramidal side effects including drug-induced Parkinsonism (rigidity, bradykinesia, tremor) and akathisia (subjective restlessness with tremulousness), typically within days to weeks of initiation 1.
Lithium causes a fine postural and kinetic tremor, particularly at therapeutic or supratherapeutic levels; risk factors include polypharmacy, older age, and immediate-release formulations 2, 3.
Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (e.g., amitriptyline) commonly induce postural tremor 3.
Valproate produces a dose-dependent postural tremor that may persist even after dose reduction 3.
Beta-adrenergic agonists (e.g., albuterol, terbutaline) and amiodarone induce postural tremor through sympathetic activation 3.
Dopamine receptor antagonists (typical and atypical antipsychotics) and VMAT2 inhibitors (e.g., tetrabenazine, valbenazine) cause parkinsonian tremor 3.
Substances of abuse—including alcohol (both intoxication and withdrawal), cocaine, and amphetamines—produce tremor through various mechanisms 3.

Clinical Pearl: Always perform a comprehensive medication review, including over-the-counter agents, supplements, and recreational substances, as polypharmacy significantly increases tremor risk 3.

Enhanced Physiologic Tremor

All individuals exhibit low-amplitude, high-frequency physiologic tremor at rest and during action, which becomes symptomatic when enhanced by:

Anxiety and psychological stress 4.
Caffeine intake 4.
Fatigue and sleep deprivation 4.
Metabolic disturbances: hyperthyroidism, hypoglycemia, hypocalcemia, hypomagnesemia 4.
Fever and systemic illness 4.

Enhanced physiologic tremor is typically bilateral, symmetric, high-frequency (8–12 Hz), and resolves when the precipitating factor is corrected 4.

Essential Tremor

Essential tremor is the most common pathologic tremor, affecting 0.4–6% of the population, with autosomal-dominant inheritance in approximately 50% of cases 4.

Characteristics: bilateral postural and kinetic tremor (4–8 Hz) predominantly affecting the upper extremities and head; may involve voice and lower extremities 4, 5.
Diagnosis: progressive course over years, family history in half of cases, improvement with alcohol intake in 50–70% 4.
Treatment: first-line agents include primidone and propranolol; benzodiazepines are second-line; deep brain stimulation is reserved for refractory cases 6, 5.

Parkinsonian Tremor

More than 70% of patients with Parkinson disease present with tremor as the initial feature 4.

Characteristics: unilateral resting tremor (4–6 Hz) with "pill-rolling" quality; decreases with voluntary movement; may have postural and kinetic components as disease progresses 4, 5.
Associated features: bradykinesia, rigidity, postural instability 4.
Treatment: anticholinergics (e.g., trihexyphenidyl, benztropine) for tremor-dominant disease; carbidopa-levodopa for motor symptoms; dopamine agonists (e.g., pramipexole, ropinirole) 5.

Diagnostic Pitfall: Drug-induced Parkinsonism from antipsychotics mimics idiopathic Parkinson disease but is typically bilateral, has earlier onset of rigidity, and lacks the classic resting tremor asymmetry 1.

Cerebellar Tremor

Cerebellar lesions (stroke, multiple sclerosis, tumor, alcohol-related degeneration) produce intention tremor—a coarse, irregular oscillation that worsens as the limb approaches a target 4, 6.

Associated signs: dysmetria, dysdiadochokinesia, ataxic gait, dysarthria 4.
Imaging: MRI brain is indicated when cerebellar signs are present 4.

Dystonic Tremor

Dystonic tremor occurs in the context of sustained muscle contractions causing abnormal postures 6.

Characteristics: irregular, jerky tremor in the affected body part; may be task-specific (e.g., primary writing tremor) 6.
Treatment: botulinum toxin injections are first-line for focal dystonic tremor 6.

Psychogenic (Functional) Tremor

Psychogenic tremor should be actively diagnosed based on positive clinical features, not as a diagnosis of exclusion 4, 6.

Diagnostic features: abrupt onset, spontaneous remission, changing tremor characteristics (frequency, amplitude, distribution), extinction with distraction, entrainment (tremor frequency changes to match a voluntary rhythmic movement in another body part) 4, 6.
Associated features: other functional neurologic symptoms, psychiatric comorbidity 4.

Metabolic and Toxic Causes

Hyperthyroidism: fine postural tremor with tachycardia, weight loss, heat intolerance 4.
Hypoglycemia: coarse tremor with diaphoresis, confusion, tachycardia 4.
Hepatic encephalopathy: asterixis (negative myoclonus/"flapping tremor") with altered mental status, hyperammonemia 1.
Uremia: asterixis with elevated creatinine, metabolic acidosis 1.
Alcohol withdrawal: coarse postural tremor 6–48 hours after last drink, with autonomic hyperactivity 3.
Wilson disease: "wing-beating" tremor (coarse, irregular, proximal upper extremity tremor) with Kayser-Fleischer rings, hepatic dysfunction 5.

Neuroleptic Malignant Syndrome (NMS)

NMS is a life-threatening complication of antipsychotic use characterized by the tetrad of altered mental status, fever, rigidity, and autonomic instability 1.

Tremor in NMS: occurs as part of extrapyramidal rigidity and hypertonicity; may present as parkinsonian-like tremor 1.
Pathophysiology: dopamine D2 receptor blockade in the nigrostriatal pathways produces muscle rigidity and tremor 1.
Incidence: 0.02–3% of patients on antipsychotics; mortality has decreased from 76% in the 1960s to <10–15% currently 1.
Management: immediate discontinuation of antipsychotic, supportive care, dantrolene or bromocriptine in severe cases 1.

Critical Red Flag: Any patient on antipsychotics presenting with fever, altered mental status, and rigidity/tremor requires urgent evaluation for NMS 1.

Diagnostic Algorithm

Categorize by activation condition:
- Resting tremor → Parkinson disease, drug-induced Parkinsonism, NMS 4, 5.
- Postural/kinetic tremor → Essential tremor, enhanced physiologic tremor, medication-induced (lithium, valproate, SSRIs), hyperthyroidism 4, 3.
- Intention tremor → Cerebellar lesion 4, 6.
- Task-specific tremor → Dystonic tremor, primary writing tremor 6.
Assess medication history: Review all prescription medications, over-the-counter agents, supplements, and substances of abuse 3.
Evaluate for metabolic causes: Check thyroid function, glucose, electrolytes (calcium, magnesium), renal function, liver function 4.
Screen for systemic illness: Fever, infection, hepatic encephalopathy 1, 4.
Neurologic examination: Assess for bradykinesia, rigidity, ataxia, dystonia, focal deficits 4, 6.
Consider functional tremor: Evaluate for abrupt onset, distractibility, entrainment, inconsistent characteristics 4, 6.

Common Pitfalls

Failing to recognize drug-induced tremor: Always consider medication side effects, especially in patients on antipsychotics, lithium, valproate, or SSRIs 1, 2, 3.
Overlooking NMS: Fever, rigidity, and tremor in a patient on antipsychotics is NMS until proven otherwise 1.
Misdiagnosing asterixis as tremor: Asterixis is a negative myoclonus (loss of postural tone), not a true tremor, and indicates metabolic encephalopathy (hepatic, uremic) 1.
Assuming psychogenic tremor is a diagnosis of exclusion: Actively look for positive features (entrainment, distractibility, inconsistency) rather than simply ruling out organic causes 4, 6.

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