Tremor in Multiple Sclerosis (MS)

Causes, Diagnostics, and Modern Treatment Approaches

What Is MS-Related Tremor?

Tremor is one of the most disabling manifestations of multiple sclerosis. According to current studies, up to 50% of patients experience it during the disease course. It impairs movement precision, object handling, self-care, and coordination.

The primary mechanism involves damage to the cerebello–thalamo–cortical pathways, which mediate fine motor control. MRI studies demonstrate:

• cerebellar and thalamic atrophy,
• demyelinating lesions in these structures,
• a direct correlation between lesion burden and tremor severity.

These findings were confirmed in neuroimaging studies by Boonstra and colleagues (2017; 2020).

MS-related tremor may cause difficulties with eating and holding objects.

Classification of Tremor in MS

Intention (kinetic) tremor

The most common form. It worsens as the limb approaches a target (e.g., during the finger-to-nose test, writing, or manipulating small objects). It is characteristic of cerebellar involvement.

Postural tremor

Occurs when holding a limb in a fixed position. May coexist with balance impairment and other signs of cerebellar dysfunction.

Rest tremor

Uncommon in MS and typically associated with additional brainstem or subcortical involvement. Pure rest tremor is not typical for MS, and its detection requires careful re-evaluation of the diagnosis and differential search.

For objective severity assessment in studies and specialized centers, the Bain tremor scale is often used.

Differential Diagnosis of Tremors

It is important to distinguish MS-related tremor from other forms of shaking, as treatment strategies and prognosis may differ substantially.

Essential tremor (ET)

The most common chronic tremor. Usually bilateral and relatively symmetric, worsening with action and posture. Often associated with a family history. Some patients experience temporary improvement after small amounts of alcohol. Unlike MS, other neurological deficits (sensory disturbances, visual changes, focal signs) are typically absent. Brain MRI generally does not show demyelinating lesions.

Parkinsonian tremor

In Parkinson’s disease, rest tremor (“pill-rolling”) is more typical and often asymmetric. It is accompanied by bradykinesia, rigidity, and characteristic gait abnormalities. It often responds well to dopaminergic therapy. The clinical picture, symptom dynamics, and treatment response differ markedly from MS-related tremor.

Functional (psychogenic) tremor

Characterized by variability, inconsistency, sudden changes in amplitude and frequency, and disappearance with distraction. “Entrainment” (synchronization with voluntary movement of another limb) is typical. Often associated with other functional neurological symptoms.

Metabolic and medication-induced tremor

Tremor may occur with thyrotoxicosis, hypoglycemia, vitamin B₁₂ deficiency, metal intoxication, and with use of certain medications (lithium, valproate, antidepressants, stimulants, etc.). Diagnosis requires medical history review, laboratory tests, and analysis of medication load.

Diagnostics of Tremor in MS

Diagnostic evaluation typically includes:

• Brain MRI with assessment of the cerebellum, brainstem, thalamus, and major pathways;
• neurological examination with coordination and gait testing;
• analysis of tremor characteristics (amplitude, frequency, triggers, posture/action dependency);
• if needed — accelerometry, handwriting analysis, video monitoring, and longitudinal follow-up.

The goal is to determine the tremor type, severity, contribution of MS activity, and exclude other causes.

Treatment of MS-Related Tremor

At present, MS-related tremor remains a challenging symptom to treat. Efficacy of most therapies is limited, so a combined approach involving a neurologist, physiotherapist, and occupational therapist is typically used.

Pharmacological treatment

No medication has demonstrated strong and reproducible efficacy in large randomized trials, but some agents may partially reduce tremor intensity in selected patients:

• Propranolol (propranolol) — may reduce postural tremor amplitude, but is usually ineffective for cerebellar tremor in MS.
• Clonazepam (clonazepam) — can reduce anxiety and tremor but is limited by sedation, fall risk, and dependence.
• Levetiracetam (levetiracetam) — showed possible benefit in small studies, but evidence remains limited.
• Carbamazepine (carbamazepine) — may help selected tremor types but is not a standard treatment for MS-related tremor.
• Isoniazid (isoniazid) — historically used at high doses for severe cerebellar tremor, but significant toxicity (hepatic and neurological) limits its use.
• Ondansetron (ondansetron) and dolasetron (dolasetron) — small studies show inconsistent results; not considered standard therapy.

Overall, pharmacotherapy remains symptomatic with limited evidence.

Cannabinoids

Cannabis-based medications, including nabiximols (Sativex) and various THC/CBD combinations, are widely discussed and frequently used by MS patients.

However, controlled clinical trials have not shown significant tremor reduction. Guidelines (including the American Academy of Neurology) state that cannabinoids are likely ineffective for tremor treatment and may cause cognitive or psychiatric side effects.

Rehabilitation (key component of treatment)

Rehabilitation is one of the most effective approaches for MS-related tremor and often provides more functional improvement than medications.

Physiotherapy

Includes trunk stabilization, strengthening of proximal muscles, coordination training, and techniques to reduce compensatory muscle tension. The goal is to minimize tremor impact on daily activities and reduce fall risk.

Occupational therapy

Helps adapt writing, eating, computer use, and fine-motor tasks. Patients learn controlled, slower movements, optimal positioning, grip techniques, and use of assistive devices.

Orthoses and stabilizing devices

Used to support function:

• weighted wrist and forearm cuffs,
• stabilizing wrist/forearm orthoses,
• adaptive utensils with stabilization systems (e.g., Liftware).

Balance and gait training

Stabilometric platforms, robotic systems, and biofeedback technologies may help reduce fall risk and improve gait confidence in patients with combined tremor and ataxia.

Limb cooling

Short-term local cooling (e.g., cooling sleeves) may temporarily reduce tremor amplitude. The effect is transient and considered adjunctive.

Technical and neuromodulation approaches

MRI-guided focused ultrasound (MRgFUS)

Used for thalamotomy in essential tremor and Parkinson’s disease. For MS tremor, this method remains experimental: reported cases and small series exist, but long-term efficacy and safety data are limited.

Tremor-stabilizing devices

Electronic bracelets and active orthoses with vibration detection and counter-phase stabilization are being developed. Small studies show functional improvement, but these technologies remain experimental and do not replace core rehabilitation.

Deep brain stimulation (DBS)

In MS, DBS is considered an experimental method for severe, refractory tremor when medication and rehabilitation provide insufficient benefit.

The most common target is the ventral intermediate nucleus (VIM) of the thalamus. Some patients show 30–60% tremor reduction, but:

• the effect may diminish over time,
• side effects may occur (dysarthria, worsened ataxia, gait instability),
• evidence is based on limited case series.

Therefore, DBS is not a standard treatment and is used only in highly selected cases.

Stereotactic thalamotomy

Surgical lesioning of part of the thalamus can reduce tremor but carries risks of permanent neurological deficits (dysarthria, impaired coordination, weakness). In MS, it is used very rarely and only in exceptional situations.

Can MS Tremor Be Completely Eliminated?

Complete resolution is uncommon. A realistic therapeutic goal is reducing tremor intensity and improving quality of life. A comprehensive approach may:

• improve movement precision,
• enhance daily and professional functioning,
• reduce fatigue and fall risk,
• provide compensation through rehabilitation and assistive devices.

When to See a Doctor

Consult a neurologist if:

• tremor worsens and interferes with work, study, or daily activities;
• new symptoms appear — severe imbalance, speech or visual changes;
• tremor appears suddenly or rapidly progresses (important to exclude MS relapse or other causes);
• you need guidance on treatment and rehabilitation options.

References

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