Ataxia may be defined as a lack of or reduction in coordination and is invariably associated with tremor (i.e., an involuntary, rhythmic, oscillatory movement of a body part). These symptoms occur in 75 percent of patients with MS and most frequently manifest as upper limb intention tremor. They are both severely disabling and embarrassing, affecting upper limb function, gait, and, in severe cases of truncal ataxia, standing and sitting balance are badly affected. The tremor of MS is frequently only one component of a complex movement disorder and the underlying mechanisms are poorly understood. Although inflammatory demyelination in different parts of the cerebellum and related areas may produce a distinct tremor, it is nonetheless extremely difficult to classify individual tremors in patients. It remains one of the most difficult symptoms to manage and is associated with a poor outcome in rehabilitation.

As with spasticity, there are practical components to the management of ataxia, which must be considered before other interventions. These include patient education, improving posture, and maximizing proximal stability during activities, and the provision of equipment. Weights have not proved to be very successful, although they may be slightly more effective if a computer damping device is incorporated. A small exploratory study of occupational therapy input suggested modest benefit. Other treatments may include drug therapy, which is limited and often not well tolerated, and more invasive surgical intervention, including thalamotomy and thalamic stimulation.

Medical Treatment for Ataxia and Tremor
Few drugs have been evaluated and none adequately. Isoniazid (with pyridoxine) has been shown to be of limited benefit in a number of small studies. It showed some effect in 10 of 13 patients, although this did not translate into improved function. Four of six patients in a second study showed sufficient benefit that they wished to continue the drug. It is thought to be more useful in postural tremor with an intention component than in pure intention tremor. Up to 1200 mg a day in divided doses has been used, increasing gradually from 200 mg twice a day. This drug, which was the first to undergo a randomized control trial for the treatment of MS, is not well tolerated and causes gastrointestinal disturbance. There has been even less evaluation of other drugs, including carbamazepine, clonazepam, and buspirone. Propranolol may useful but higher doses, which may be poorly tolerated, are often required. Although a single-blind, cross-sectional study evaluating the role of carbamazepine in cerebellar tremor in 10 patients (7 with MS) suggested some benefit, it has also been suggested that this agent worsened ataxia. More recently, the 5-HT3 antagonist ondansetron has been evaluated, given by both intravenous and oral routes. Although the studies of the former looked promising, the more recent placebo-controlled, double-blind, parallel-group study of oral therapy was negative. Fifty-two patients, the majority of whom had MS, were randomized, and the treatment arm received 8 mg per day for 1 week. Although some benefit in the nine hole peg test was seen in the treated arm, there was no difference between the groups on a global ataxia rating scale. A small study of cannabinoids in the treatment of ataxia failed to show any beneficial effect.

Surgical Intervention in Ataxia and Tremor
Although thalamotomy of the ventral intermediate nucleus (VIN) has been shown to be beneficial in the tremor of Parkinson’s disease, there has been limited evaluation of its role in tremor relating to MS. In general, it is not considered to be as effective in this condition. In selected patients with MS, thalamotomy has been reported to alleviate contralateral limb tremor, initially in approximately 65 to 96 percent of cases, although in about 20 percent tremor returns within 12 months. Functional improvement is estimated to occur in 25 to 75 percent of patients. A recent study of unilateral thalamotomy compared 13 patients with 11 controls and showed improvement in tremor and improved function at 12 months in the treated group. Side effects are more common in bilateral procedures (often required in MS) and may occur in up to 45 percent of patients. Possible side effects include hemiparesis, dysphasia, and dysphagia in up to 10 percent of patients. Experience suggests that optimum results are obtained in patients with relatively stable disease, good mobility, and minimal overall disability status—an extremely small group.

Thalamic stimulation has been shown to alleviate tremor in up to 69 percent of patients in studies involving 13, 5, and 15 patients, respectively. Patients were carefully selected; for example, in one study the 5 patients reported were from an initial group of 17 patients, and no control study has yet been carried out. Serious side effects may occur. In one recent study comparing thalamic stimulation with lesioning, it is suggested that stimulation is associated with fewer side effects. Other approaches, including extracranial application of brief AC-pulsed electromagnetic fields, dynamic systems with multi-degree of freedom orthoses, and robotic arms based on virtual reality, have not been adequately evaluated.

In the view of the Committee, ataxia and associated tremor are among the most resistant and disabling symptoms to manage. Current strategies are of limited benefit, but information on the benefits of surgical intervention is accumulating.