Tremor in Multiple Sclerosis: Prevalence, Cause and Treatment
Tremor, or uncontrolled shaking, is a highly disabling symptom of multiple sclerosis which is often associated with a more advanced disease course. Tremor, an involuntary, rhythmic, muscle movement caused by repetitive contraction and relaxation of paired muscle groups, has long been recognized as a feature of MS. The French neurologist Dr. Jean-Martin Charcot (1825-1893) categorized it with nystagmus and scanning speech (Rascol, 1982).
A study published in the open-access journal Tremor and Other Hyperkinetic Movements reviewed recent advancements in the understanding of tremors in MS. The review explores the prevalence and clinical features of tremors in MS, including physical cause of tremors, and treatment methods, including surgery and/or prescription medications.
Reviewers searched MEDLINE with the terms "multiple sclerosis" and "tremor," published between January 1966 and May 2012. My own search revealed articles dating back to 1958, and at least six additional relevant articles published since May 2012.
Prevalence of tremor in MS
Studies indicate that tremors are prevalent in 25% to 58% of the MS population. Upper limb tremor was described in 58% of 100 randomly selected MS patients from an MS specialty clinic in London (potential for selection bias); 27% with minimal tremor, 16% with mild tremor, and 15% with moderate to severe tremor (Alusi, 2001). In a community-based study of 200 MS patients in Olmsted County, Minnesota, tremor was noted in 25.5% of patients with severe tremor seen in only 3% of patients (Pittock, 2004).
Authors note that the prevalence of tremor in MS is difficult to establish because of the transient nature of MS symptoms, the lack of assessment for tremor in the EDSS, and the difficulty in distinguishing intention tremor from ataxia.
Assessment of tremor in MS
Tremor is an involuntary, repetitive, rhythmic movement of a body part. A tremor present during rest (muscle relaxation) is different than an action tremor which is produced during voluntary movement. The type of tremors seen in MS are action tremors, specifically postural tremor and/or intention tremor, often involving the arms, head, neck, and trunk. Vocal cords by also be affected.
Tremors which are not commonly seen in MS include rest tremor, task-specific tremor (such as while writing, for example), and simple kinetic tremor present during voluntary non-target-directed motions (such as opening and closing a fist). In general, movement disorders other than tremor are uncommon in MS (Labiano-Fontcuberta, 2012).
Tremor classification and severity scales have not been widely adopted in MS practice. One scale, the Fahn-Tolosa-Marin Tremor Rating Scale, was adapted and tested for reliability in a study, but not for validity. A 0-10 tremor severity scale devised by Bahn and colleagues in 1993 has been tested for validity and reliability in use with the MS population. However, it has only been used in a few clinical studies, according to review authors.
Cause of tremor in MS
Because MS is a disease which involves variable areas of the central nervous system, with almost infinite combinations of damaged areas and symptoms possible, the underlying cause of tremor is difficult to ascertain or link directly to specific lesions in the brain. However, studies have supported a link between the cerebellum and MS-related tremor.
Tremor and disability in MS
Tremors typically develop in MS patients sometime around 11 years after disease onset, making them signs of advancing MS (Alusi, 2001). In studies, tremor has been associated with more severe disability. Patients with tremor are more likely to be wheelchair dependent and have worse EDSS scores (Alusi, 2001). In fact, patients who show signs of cerebellar damage early on in the disease tend to develop severe disability more quickly (Amato, 2000). Some signs of cerebellar involvement in MS include disturbed balance, gait ataxia (wide, staggering, or shuffling walk), poor muscle tone, and nystagmus. In the Olmsted County study, patients with tremor were more likely to be unemployed or to have retired early because of disability.
Treatment of tremor in MS
Physical aids which may be helpful in patients with mild tremor include the use of electromagnetic fields, limb cooling, weight bracelets, orthoses, and physiotherapy. In studies, the effect of limb cooling on intention tremor lasted for at least 30 minutes. Some patients may benefit from restricting caffeine intake or other stimulants which increase symptoms. Relaxation methods aimed at alleviating the anxiety or stress may help other patients for whom these symptoms make their tremors worse.
Available medications aimed at treating tremors are unsuccessful in most cases, according to review authors. Patients have experienced some relief from other drugs, including an anticonvulsant (primidone), sedative (glutethimide), tuberculosis medication (isoniazid,) and intrathecal baclofen. Marijuana has been been found to have no positive effect on tremors in several randomized controlled trials. The anti-seizure medication, levetiracetam, has been studied but its benefit is unclear. Studies have explored the use of topiramate (Topamax), a migraine medication, in treating tremor and ataxia in MS patients. Results look promising.
Options for surgical treatment include stereotactic thalamotomy, a procedure that severs nerve fibers from an area of the brain called the thalamus, and deep brain stimulation (DBS) which involves implantation of small electrodes in the brain to stimulate and change brain activity. Stereotactic thalamotomy has been used since 1960 to combat MS tremor (Cooper, 1967). One study reported positive use of gammaknife thalamotomy, but further studies have not been published.
Three studies have compared thalamotomy and DBS in MS patients. Schuurman et al. (2000) did not find significant differences between thalamotomy and DBS in functional outcome for a subgroup of MS patients. Yap et al. (2007) concluded that both thalamotomy and thalamic DBS were comparable procedures for tremor suppression, each associated with adverse effects. In a nonrandomized study, thalamotomy was more effective in treating MS tremor, with 78% reduction of postural tremor and 72% reduction for intention tremor, than deep brain stimulation, which showed 64% and 36% reduction, respectively (Bittar, 2005). DBS is currently the accepted surgical intervention for MS tremor, however larger clinical trials comparing both interventions are needed. Long-term follow-up is also needed to determine which intervention(s) may result in persistent improvement.
Alusi SH, et al. A study of tremor in multiple sclerosis. Brain 2001;124:720-730.
Amato MP, Ponziani G. A prospective study on the prognosis of multiple sclerosis. Neurolog Sci 2000; 21:S831-S838.
Bittar RG, et al. Thalamotomy versus thalamic stimulation for multiple sclerosis tremor. J Clin Neurosci 2005;12:638-642.
Cooper IS. Relief of intention tremor of multiple sclerosis by thalamic surgery. JAMA 1967;199:689-694.
Labiano-Fontcuberta A, Benito-LeÃ³n J. Understanding Tremor in Multiple Sclerosis: Prevalence, Pathological Anatomy, and Pharmacological and Surgical Approaches to Treatment. Tremor Other Hyperkinet Mov (N.Y.) 2012 Sep 14;2012(2). pii:109
Pittock SJ, et al. Prevalence of tremor in multiple sclerosis and associated disability in the Olmsted County population. Mov Disord 2004;19:1482-1485.
Schuurman PR, et al. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med 2000;342:461-468.
Yap L, Kouyialis A, Varma TR. Stereotactic neurosurgery for disabling tremor in multiple sclerosis: thalamotomy or deep brain stimulation? Br J Neurosurg 2007;21:349-354.