2018 Consensus Statement (IPMDS Task Force)

• Axis 1 — Clinical features: body distribution, activation condition, frequency, associated signs
• Axis 2 — Etiology: acquired vs. genetic vs. idiopathic
• Replaces prior classification (e.g., “benign essential tremor”); emphasizes tremor syndromes over single diseases
• ET redefined: isolated bilateral upper limb action tremor ≥3 yr duration without other neurological signs
• ET plus: ET with additional soft signs (rest tremor, impaired tandem gait, mild memory impairment, questionable dystonic posturing)

Rest vs. Action Tremor

Frequency Ranges

Clinical Features

• Most common pathologic tremor; prevalence ~1% (up to 5% in age >65)
• Bilateral action tremor (postural + kinetic) of the upper limbs, usually symmetric
• Frequency: typically 6–12 Hz (slows with age); amplitude increases, frequency decreases with age
• Body distribution: hands (95%) > head (34%) > voice (12%) > jaw/face > lower limbs
• Head tremor: “yes-yes” (vertical) or “no-no” (horizontal); absent at rest
• Alcohol responsiveness: ~50–75% improve with ethanol — hallmark feature (temporary, rebound worsening)
• Family history positive in ~50%; autosomal dominant with variable penetrance
• Duration criterion: ≥3 years of bilateral upper limb action tremor

ET vs. Parkinsonian Tremor

Treatment

First-Line Pharmacotherapy

• Propranolol: 60–320 mg/d (start 10–20 mg BID, titrate); long-acting preferred; ~50% tremor amplitude reduction; Level A evidence
• Primidone: 12.5–25 mg qhs starting dose; target 250–750 mg/d; first-dose phenomenon (nausea, sedation, ataxia); Level A
• Propranolol and primidone are equally effective and can be combined
• Propranolol contraindicated in asthma, decompensated HF, severe bradycardia

Second-Line & Adjuncts

• Topiramate: 50–400 mg/d (typical effective 200–400 mg); Level B evidence; weight loss, cognitive side effects
• Gabapentin: 1200–3600 mg/d; Level B; useful as add-on
• Alprazolam: 0.75–2.75 mg/d; Level B; risk of dependence — use cautiously
• Clonazepam: useful adjunct, especially for orthostatic/task-specific tremor
• Botulinum toxin: Level B for hand tremor; Level C for head/voice; dose-dependent weakness

Surgical Options

• DBS of VIM (ventral intermediate) thalamus: gold standard for medication-refractory ET; ~70–90% tremor reduction
• MRI-guided focused ultrasound (MRgFUS): VIM thalamotomy; non-invasive; FDA-approved for ET (unilateral 2016; STAGED BILATERAL approved 2022 with interval between sides)
• Gamma Knife thalamotomy: VIM target; delayed onset of benefit (weeks–months); unilateral
• Bilateral thalamotomy/lesioning carries risk of dysarthria — bilateral DBS preferred when needed

Overview

• Exaggeration of normal physiologic tremor (8–12 Hz); fine, low-amplitude, postural
• Bilateral and symmetric; typically affects outstretched hands
• Resolves when the underlying cause is treated — NOT a chronic tremor disorder

Causes (Mnemonic: “TEMPA”)

• Thyroid (hyperthyroidism), thermoregulation (fever)
• Emotional stress, exercise, epinephrine excess (pheochromocytoma)
• Medications: β-agonists (albuterol), lithium, valproate, amiodarone, SSRIs, caffeine, theophylline, corticosteroids
• Physiologic states: fatigue, sleep deprivation, hypoglycemia
• Abstinence: alcohol/benzodiazepine withdrawal

Management

• Identify and treat the underlying cause (correct thyroid, discontinue offending drug, treat anxiety)
• Reassurance — tremor resolves once the trigger is removed
• Propranolol may provide symptomatic relief if cause cannot be immediately corrected

Clinical Features

• Intention tremor: amplitude progressively increases as the limb approaches the target
• Low frequency: typically 3–5 Hz
• Ipsilateral to the cerebellar lesion
• Finger-to-nose and heel-to-shin testing: worsens at the target (terminal oscillation)
• Often accompanied by other cerebellar signs: dysmetria, dysdiadochokinesia, ataxic gait, hypotonia, nystagmus
• Postural component may also be present (postural + intention = cerebellar)

Localization

• Dentate nucleus: primary generator of cerebellar intention tremor
• Superior cerebellar peduncle (SCP): efferent pathway (dentatorubrothalamic tract); lesion here → contralateral intention tremor
• Cerebellar hemispheres: appendicular ataxia + intention tremor (ipsilateral)
• Vermis lesions → truncal ataxia, wide-based gait (less tremor)

Etiologies

• Multiple sclerosis (most common cause in young adults), stroke, tumor, spinocerebellar ataxia
• Chronic alcohol cerebellar degeneration (predominantly vermal → gait > limb)
• Paraneoplastic cerebellar degeneration (anti-Yo, anti-Hu antibodies)

Treatment

• No reliably effective pharmacotherapy — often refractory
• Trials of isoniazid (600–1200 mg/d + pyridoxine), clonazepam, levetiracetam — limited evidence
• Wrist weights may reduce amplitude in some patients
• DBS (VIM thalamus or dentate) under investigation; less effective than DBS for ET

Clinical Features

• Irregular, jerky tremor occurring in a body part affected by dystonia
• Often position-specific with a “null point” — a position where tremor diminishes or disappears
• Amplitude and direction may vary (unlike regular sinusoidal tremor of ET or PD)
• Geste antagoniste (sensory trick): light touch to the affected area reduces tremor (same as in dystonia)
• May be the presenting feature of dystonia before overt dystonic posturing becomes apparent

Tremor Associated with Dystonia vs. Dystonic Tremor

• Dystonic tremor: tremor in a body part WITH dystonia (e.g., tremulous cervical dystonia)
• Tremor associated with dystonia: tremor in a body part NOT affected by dystonia in a patient who has dystonia elsewhere
• Both may mimic ET — look for subtle dystonic posturing, null point, and irregularity

Treatment

• Botulinum toxin: first-line, especially for cervical dystonic tremor
• Anticholinergics (trihexyphenidyl), clonazepam, baclofen
• DBS of GPi for generalized or severe segmental dystonic tremor

Clinical Features

• Combination: rest + postural + intention tremor in the same limb — “all three types”
• Low frequency: <5 Hz (typically 3–4.5 Hz)
• Large amplitude, irregular, highly disabling
• Delayed onset: appears weeks to months (typically 4 weeks to 2 years) after the causative lesion
• Contralateral to the lesion

Pathophysiology & Localization

• Lesion in the midbrain/upper brainstem (historically called “rubral tremor”) affecting:
• Cerebellothalamic fibers (SCP/dentatorubrothalamic tract) → intention component
• Nigrostriatal dopaminergic fibers → rest tremor component
• Typically involves both cerebellothalamic (necessary) and nigrostriatal pathways; dopaminergic involvement is common but not invariable
• Common causes: stroke (midbrain/thalamic), MS, tumor, trauma

Treatment

• Pharmacotherapy often disappointing; try levodopa (for rest component), clonazepam, propranolol
• DBS (VIM thalamus or combined VIM + VOp) — limited case reports/series
• Treat the underlying cause when possible

Orthostatic Tremor

• High frequency: 13–18 Hz (fastest tremor in neurology)
• Occurs exclusively on standing; resolves with walking, sitting, or lying down
• Patients describe leg unsteadiness/instability while standing still, NOT classic visible shaking
• Patients often report feeling better when touching a wall or leaning on an object (light haptic contact dampens the tremor) — high-yield bedside clue often tested on boards
• Diagnosis: surface EMG of leg muscles while standing shows coherent 13–18 Hz bursts
• Treatment: clonazepam (most effective), gabapentin, valproate; often refractory

Palatal Tremor (Palatal Myoclonus)

Primary Writing Tremor

• Task-specific tremor occurring only during writing
• Type A: tremor appears during writing (task-induced)
• Type B: tremor appears when assuming the writing position even without writing (position-specific)
• Debated: variant of ET vs. variant of dystonia
• Treatment: propranolol, primidone, botulinum toxin (hand extensors)

Neuropathic Tremor

• Postural/kinetic tremor in the setting of peripheral neuropathy
• Most commonly associated with demyelinating neuropathies: IgM paraproteinemic (anti-MAG), CIDP, CMT
• Mechanism: loss of proprioceptive input → impaired sensory feedback → tremor
• Treatment: treat underlying neuropathy; propranolol may help symptomatically

Functional (Psychogenic) Tremor

• Most common functional movement disorder
• Variable frequency and amplitude; abrupt onset; spontaneous remissions
• Entrainment: tremor frequency shifts to match a rhythmic task performed by the contralateral limb — most reliable sign
• Distractibility: tremor diminishes or stops with cognitive tasks or contralateral finger tapping
• Co-activation sign: examiner feels increased tone/resistance when attempting to elicit tremor passively
• DaTscan normal; EMG shows variable burst duration (vs. regular in organic tremor)

Genetics

• FMR1 premutation: 55–200 CGG repeats in the FMR1 gene (5′ UTR)
• X-linked inheritance; males more severely and frequently affected
• Distinct from Fragile X syndrome (full mutation >200 CGG repeats → intellectual disability)
• Premutation carriers were historically considered unaffected — FXTAS reframes them as at-risk

Clinical Features

• Typical onset in men >50 years with FMR1 premutation
• Intention tremor (cerebellar) + progressive cerebellar ataxia — core features
• Parkinsonism (rigidity, bradykinesia; often L-dopa poorly responsive)
• Cognitive decline (executive dysfunction, dementia)
• Autonomic dysfunction (orthostatic hypotension, bowel/bladder, impotence)
• Peripheral neuropathy may coexist

Imaging

• MCP sign: bilateral T2 hyperintensity of the middle cerebellar peduncles — pathognomonic for FXTAS
• Also: cerebellar atrophy, splenium of corpus callosum T2 hyperintensity, generalized white-matter disease

Female Carriers

• Women with the FMR1 premutation can develop ataxia (less common, milder, later onset than men)
• Fragile X-associated primary ovarian insufficiency (FXPOI): premature ovarian insufficiency in ~20% of female premutation carriers

Genetic Counseling

• Offspring implications: premutation can expand to a full mutation (>200 CGG) when transmitted by the mother → Fragile X syndrome in children
• Test FMR1 in any older man with combined intention tremor + cerebellar ataxia + parkinsonism, especially with family history of intellectual disability or premature ovarian insufficiency
• Refer to genetics for family counseling once diagnosis is confirmed

Clinical Assessment

• Observe at rest (hands in lap), with arms outstretched (postural), during finger-to-nose (intention)
• Note symmetry, frequency, amplitude, body distribution, activation conditions
• Check for associated signs: bradykinesia, rigidity, dystonic posturing, cerebellar signs
• Assess handwriting (large/tremulous in ET vs. micrographia in PD)
• Spiral drawing: large amplitude oscillations in ET; tight small spiral in PD
• Alcohol history (ET improves), medication review, family history

DaTscan (Ioflupane I-123 SPECT)

• Images presynaptic dopamine transporter (DAT) in the striatum
• Abnormal (reduced uptake): PD, MSA, PSP, DLB, CBD — any neurodegenerative parkinsonism
• Normal: ET, enhanced physiologic tremor, dystonic tremor, drug-induced parkinsonism, functional tremor
• Key indication: differentiate ET from tremor-dominant PD when clinical exam is uncertain
• Does NOT distinguish between different parkinsonian syndromes (PD vs. MSA vs. PSP)

Laboratory Studies

• TSH: rule out hyperthyroidism (enhanced physiologic tremor)
• Ceruloplasmin + serum copper + 24-h urine copper: Wilson disease in patients <50 years with any movement disorder
• Liver function, ammonia: hepatic tremor (acquired hepatocerebral degeneration)
• BMP (calcium, glucose), medication/toxin screen as indicated
• Anti-MAG, SPEP/UPEP: if neuropathic tremor suspected

Neuroimaging

• MRI brain: structural lesions (midbrain for Holmes tremor, cerebellum for cerebellar tremor, inferior olive for palatal tremor)
• SWI/GRE sequences: microhemorrhages, calcification
• Not routinely needed for classic ET presentation

Electrophysiology

• Surface EMG: tremor frequency, regularity, burst duration; essential for orthostatic tremor (13–18 Hz)
• Accelerometry: quantifies tremor amplitude and frequency objectively
• NCS/EMG: if neuropathic tremor suspected (demyelinating features)
• Variable burst duration and entrainment on EMG suggest functional tremor