Injections of botulinum toxin A (Botox) were a significant help to multiple sclerosis patients whose disease causes arm tremors, according to a small study reported here.

In a placebo-controlled crossover trial involving 25 patients, Botox injected into the affected muscles significantly improved the tremors, said Anneke van der Walt, MBChB, of Royal Melbourne Hospital in Australia.

The treatment also allowed many of the patients to again perform simple activities such as handwriting and drinking from open cups that the tremors had made difficult or impossible, van der Walt told attendees at the joint meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis.

Currently there is no specific treatment for MS-related tremors, she explained. The present standard of care involves anticonvulsant drugs such as levetiracetam (Keppra) or carbamazepine, with a variety of other agents often used as well. These include benzodiazepines, beta-blockers, and even the anti-nausea drug ondansetron.

Van der Walt described these medications as "unrewarding" and indicated that nonsurgical approaches such as thalamotomy and deep brain stimulation had substantial side effects and lacked confirmation of long-term efficacy.

Botox, on the other hand, is considered safe when injected carefully and has been found helpful in a host of conditions involving abnormal muscle activity, ranging from overactive bladder to migraine.

The 25 patients in the study included some with bilateral tremors, such that a total of 33 arms were treated and evaluated, after excluding one dropout and two patients who experienced MS relapse during the study. About three-quarters of participants had secondary progressiveMS, with mean disease duration of 17 years (SD 8.5) and mean duration of tremor of 6.5 years (SD 5.1).

The median of both EDSS disability score and Unified Dystonia Rating Scale score was 5.5.

Patients received injections of botulinum toxin A or placebo targeted to their specific tremor patterns. A maximum of 100 IU of Botox was given in each injection.

Evaluations were conducted at baseline and six and 12 weeks after the treatment. At that point, participants crossed over to the other treatment for an identical series of injections and assessments.

The primary outcome measure was change from baseline in Bain scores for ability to hand-write a standard sentence, drawing of an Archimedes spiral, and a composite of tremor severity.

A variety of other ratings were secondary outcomes. These included scores for postural, action, intention, and rest tremors as well as for abilities to perform ordinary tasks such as drawing straight lines, pouring liquids, and drinking from a cup.

Videos were taken at baseline and at each post-treatment evaluation of participants performing these tasks.

Van der Walt showed clips of one middle-age male patient who had major improvement following the toxin injections.

At baseline, the man's left hand shook violently as he tried to write on a piece of paper and to hold a cup to his lips.

The "after" video showed him successfully drawing the Archimedes spiral, pouring water into a container without spilling, and drinking from a cup. However, it wasn't a total cure, as his hand still shook noticeably during these activities.

For all 33 arms included in the study, the mean decrease in Bain scores for tremor severity following the active Botox injections was about 2.0 at six and 12 weeks. The writing and drawing scores both declined by close to 1.0.

Very slight increases in Bain scores for all three components were seen in the averages following placebo injections, van der Walt reported. P values for all comparisons between Botox and placebo were less than 0.001.

Postural and action tremors both showed significantly greater improvement with Botox than with placebo at the six- and 12-week evaluations. However, resting and intentional tremors did not improve.

Not all participants showed significant improvements in all functional tasks at both evaluations, though when statistical significance was lacking the trend was still strong.

For example, improvements in ability to drink from a cup fell just short of significant at six weeks (P=0.069) but reached significance at 12 weeks (P=0.009). The opposite pattern was seen for pouring water into a container.

The major adverse effect associated with toxin injections was weakness in the injected arm, van der Walt said. It was reported in 42% of Botox-treated arms versus 6% of those receiving placebo shots.

None of the weakness was severe, she added; most was rated as moderate, defined as feeling weak but still able to use it.

In all cases, moreover, the weakness did not last beyond two weeks after the injections.

In response to an audience question, van der Walt said that many participants had continued to receive Botox injections in the hospital's outpatient clinic and there seemed to be no loss of effectiveness with repeated treatment. The weakness effect also appeared to decline with additional injections.

Session co-moderator Jürg Kesselring, MD, of the Neuroscience Center in Zurich, Switzerland, complimented van der Walt on the research.

"This is important because we are so desperate for something to offer our tremor patients," he said.

The study was funded by the RMH Neuroscience Foundation and Box Hill MS Research Fund. Allergan provided Botox free of charge.

Van der Walt reported grant funding and/or direct payments from Bayer, Biogen Idec, Merck Serono, and GlaxoSmithKline.

Kesselring has served on trial oversight committees and/or advisory boards for Biogen, Novartis, Serono, Schering, and Wyeth.

Primary source: ECTRIMS/ACTRIMS Triennial Meeting
Source reference:
van der Walt A, et al "Botulinum toxin type A for the treatment of disabling tremor in multiple sclerosis: a double-blind, randomised controlled study" ECTRIMS/ACTRIMS 2011; Abstract 50.

Source: MedPage Today © 2011 Everyday Health, Inc.(21/10/11)