Tremors: A Comprehensive Overview

Definition

• Adams and Victor's Principles of Neurology, 12th Edition

Classification Framework

1. Activation conditions - when the tremor appears (rest vs. action)
2. Etiology/Syndrome - the underlying cause

Major Types of Tremor

Summary Table (from Adams and Victor's)

1. Physiologic Tremor

• Frequency: 8-13 Hz in the hands; as slow as 6.5 Hz elsewhere
• Mechanism: Driven peripherally by mechanical-reflex oscillations and centrally by synchronized motor neuron discharges
• Not pathologic in itself

Enhanced (Exaggerated) Physiologic Tremor

• Physiologic states: Anxiety, fear, fright, exercise, fatigue
• Metabolic: Hyperthyroidism, hypoglycemia, hypercortisolism, pheochromocytoma, hypothermia
• Drugs and toxins: Lithium, nicotinic acid, xanthines (caffeine, aminophylline), cocaine, methamphetamine, corticosteroids, valproate, SSRIs, bronchodilators, cyclosporine, tacrolimus
• Withdrawal: Alcohol, benzodiazepines, barbiturates
• Mechanism: Enhancement in metabolic/toxic states is primarily due to stimulation of muscular beta-adrenergic receptors by elevated circulating catecholamines - NOT a CNS-mediated effect
• Treatment: Remove the cause; beta-adrenergic antagonists (propranolol)

2. Resting Tremor (Parkinsonian Tremor)

• Frequency: 3-5 Hz (some sources state 5-7 Hz)
• Location: Hands and forearms (most common), fingers, feet, lips, tongue, chin - notably not the head (head tremor favors essential tremor)
• Classic appearance: "Pill-rolling" tremor - appears as if the patient is rolling something between the thumb and other fingers
• Pattern: Asymmetrical at onset
• Enhanced by: Emotional stress, mental distraction (e.g., asking the patient to perform mental arithmetic while hands rest)
• Decreased by: Voluntary movement

3. Action Tremors

a) Postural Tremor

• Occurs when a body part is maintained against gravity (e.g., arms held outstretched)
• Absent at rest; appears with muscle activation
• Best examples: Essential tremor, enhanced physiologic tremor

b) Kinetic Tremor

• Occurs during voluntary movement (not specifically goal-directed)
• Simple kinetic tremor: during any movement
• Task-specific tremor: only during particular tasks (e.g., writing, speaking)
• Primary writing tremor - a task-specific tremor that only occurs when writing or adopting a writing posture; no tremor in other conditions; frequency ~5-7 Hz

c) Intention Tremor (Goal-directed kinetic tremor)

• Tremor that increases in amplitude as the limb approaches a target
• Classic sign of cerebellar disease (appendicular cerebellar ataxia)
• Demonstrated by: Finger-nose-finger test, heel-shin test
• Also accompanied by: Dysmetria, dysdiadochokinesia, dysarthria, wide-based gait
• Frequency: 2-4 Hz (lower frequency, coarser)
• Pathophysiology: Loss of cerebellar modulation of motor output; the lateral cerebellar hemispheres and dentato-rubro-thalamo-cortical pathway are disrupted

d) Isometric Tremor

• Occurs during sustained muscle contraction without movement (e.g., squeezing a rigid object)

4. Essential Tremor

• Frequency: 4-8 Hz (usually lower end of range), lower than physiologic tremor
• Location: Hands/arms (most common), head (titubation), vocal cords ("shaky voice"), tongue, lips; legs and trunk less often
• Pattern: Bilateral but may be asymmetrical
• Classic trigger: Posture and movement (postural + kinetic); absent at rest early on
• Worsened by: Anxiety, emotion, exercise, fatigue, caffeine
• Characteristic: Improves transiently with alcohol (a key differentiator from Parkinsonian tremor)
• Genetics: Autosomal dominant with high penetrance; previously called familial, benign, or senile tremor
• Functional impact: Can progress to illegible handwriting, inability to bring utensils or a glass to the mouth without spillage

• First-line: Propranolol (beta-blocker) or primidone (antiepileptic)
• Second-line: Topiramate, gabapentin, clonazepam
• Alcohol (temporary, not a clinical option due to risk)
• Surgical: Thalamotomy (lesion of Vim) or DBS of the Vim nucleus - highly effective
• Focused ultrasound thalamotomy (newer option)

5. Cerebellar Tremor

• Intention tremor is the hallmark (see above), but cerebellar lesions also cause:
  • Postural tremor at rest with limbs held in space (trunk and head titubation - associated with vermis lesions)
  • Frequency: 2-4 Hz, coarse, low-frequency
• Associated signs: Dysmetria, dysarthria, nystagmus, ataxic gait, hypotonia
• Causes: Multiple sclerosis, stroke, tumors, alcohol-related cerebellar degeneration, spinocerebellar ataxias

6. Holmes Tremor (Rubral Tremor / Midbrain Tremor)

• A combination of rest + postural + intention tremor - the only tremor type with all three components
• Frequency: 2-4 Hz, low-frequency, often violent
• Usually unilateral
• Low amplitude at rest, but becomes coarse and violent as the limb is raised slightly or when movement is attempted
• Mechanism: Lesion involving the superior cerebellar peduncle (dentato-rubro-thalamic tract) near the red nucleus (midbrain)
• Causes: Multiple sclerosis, brainstem infarcts (midbrain stroke), trauma
• Can resemble the wing-beating tremor of Wilson's disease
• Neuroanatomy through Clinical Cases, 3rd Edition

7. Orthostatic Tremor

• A distinctive high-frequency (14-16 Hz) tremor, the fastest of all tremor types
• Occurs exclusively in the legs shortly after standing still; disappears when sitting, lying down, or walking
• Patients feel unsteady and have a tendency to fall if stationary
• Difficult to see visually; best diagnosed by palpating the thigh muscles while the patient stands or by EMG showing characteristic ~16 Hz bursts
• Treatment: Clonazepam, valproate, gabapentin
• Adams and Victor's Principles of Neurology

8. Palatal Tremor (formerly Palatal Myoclonus)

• Rhythmic movement of the soft palate at 0.5-5 Hz (60-100/min)
• Can extend to the face, pharynx, and proximal upper extremities
• Famous for persisting during sleep - a distinguishing feature from most other tremors
• May cause ear clicking due to Eustachian tube movement
• Two forms:
  • Symptomatic: Due to lesions of the central tegmental tract or dentate-red nucleus-inferior olive circuit (infarcts, MS, trauma); associated with olivary hypertrophy on MRI
  • Essential palatal tremor: No known cause; accompanied by ear clicking
• Treatment: Botulinum toxin injections into the tensor or levator veli palatini
• Neuroanatomy through Clinical Cases, 3rd Edition

9. Neuropathic Tremor

• Action tremor (relatively symmetric) associated with peripheral neuropathies
• Especially linked to chronic inflammatory demyelinating polyneuropathy (CIDP) and IgM paraproteinemic neuropathy
• Frequency: 4-7 Hz, involves hands
• Associated with positive Romberg sign and other neuropathy features
• Mechanism: Disruption of peripheral sensory feedback loops that normally damp tremor

10. Dystonic Tremor

• Tremor occurring in a body part affected by dystonia
• Irregular, jerky rhythm (not smooth sinusoidal oscillation)
• Location is concordant with the focal dystonia (e.g., cervical dystonic tremor with torticollis)
• May appear as head tremor, hand tremor, or voice tremor in the context of dystonia
• Treatment: Botulinum toxin injections; geste antagoniste (sensory trick) may temporarily suppress it

11. Drug-Induced Tremors

• Neuroleptics/antipsychotics - parkinsonian rest tremor
• Lithium - postural/action tremor, toxic doses → coarse tremor
• Valproate - action tremor (dose-dependent)
• Beta-adrenergic agonists (salbutamol, terbutaline) - enhanced physiologic
• SSRIs, tricyclics - enhanced physiologic
• Corticosteroids - enhanced physiologic
• Calcium channel blockers, amiodarone
• Immunosuppressants: cyclosporine, tacrolimus - can cause severe tremor
• Alcohol withdrawal - coarse postural/action tremor
• Management: Dose reduction or withdrawal of offending agent; beta-blockers if needed

12. Functional (Psychogenic) Tremor

• Abrupt onset, static course, spontaneous remissions
• Variable frequency (more specific than variable amplitude alone)
• Entrainment sign: When asked to copy a rhythmic tapping with the unaffected hand at a different frequency - the affected limb entrains to the same rhythm, stops, or the patient cannot copy the movement
• Ballistic movement test: Brief stopping of tremor during fast ballistic movements with the other hand
• Distractibility: Tremor diminishes with mental distraction (mental arithmetic) - opposite to organic tremor
• Loading sign: Adding wrist weights worsens functional tremor (organic tremor improves with loading)
• Coactivation sign: Simultaneous agonist-antagonist activation, resembling voluntary shivering
• Coherence: If bilateral, both limbs tremor at the exact same frequency (organic tremors have slightly different frequencies in different limbs)
• Unresponsive to antitremor drugs; responds to psychotherapy/physiotherapy
• Normal dopamine transporter (DaT) scan
• Bradley and Daroff's Neurology in Clinical Practice

Pathophysiology: Common Neural Circuits

• Are arranged somatotopically
• Respond to kinesthetic inputs from involved muscles/joints
• Project to premotor cortex via the ventrolateral thalamo-cortical pathway
• Ultimately drive tremor via the lateral corticospinal tract

Differential Diagnosis: Key Distinguishing Features

Treatment Overview

Recent Evidence Note

• Adams and Victor's Principles of Neurology, 12th Edition - Chapter 4: Tremor, Myoclonus, Focal Dystonias
• Neuroanatomy through Clinical Cases, 3rd Edition - Chapter 16: Movement Disorders
• Bradley and Daroff's Neurology in Clinical Practice - Functional/Psychogenic Movement Disorders
• MDS Task Force Classification of Tremor (Frontiers in Neurology, 2021)
• RACGP Tremor Review 2024