Repetitive transcranial magnetic stimulation for the treatment of amyotrophic lateral sclerosis or motor neuron disease

  • Review
  • Intervention

Authors


Abstract

Background

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a progressive neurodegenerative disease without effective therapies. Several studies have suggested that repetitive transcranial magnetic stimulation (rTMS) may have positive benefit in ALS. However, the efficacy and safety of this therapy remain uncertain.

Objectives

We aimed to determine the clinical efficacy and safety of rTMS for treating ALS.

Search methods

We searched the Cochrane Neuromuscular Disease Group Specialized Register (July 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2010), MEDLINE (1966 to July 2010), EMBASE (1980 to July 2010), CINAHL (1937 to July 2010), Science Citation Index Expanded (January 1945 to June 2010), AMED (January 1985 to July 2010) and the Chinese Biomedical Database (1979 to September 2010). We also searched for ongoing studies on clinicaltrials.gov (September 2010).

Selection criteria

Randomised and quasi-randomised controlled trials assessing the therapeutic efficacy and safety of rTMS for patients with a clinical diagnosis of ALS.

Comparisons eligible for inclusion were:

1. rTMS versus no intervention;

2. rTMS versus sham rTMS;

3. rTMS versus physiotherapy;

4. rTMS versus medications;

5. rTMS + other therapies or drugs versus sham rTMS + the same therapies or drugs;

6. different methods of application of rTMS such as high-frequency (> 1Hz) compared to low-frequency (≤ 1Hz) rTMS.

Data collection and analysis

Two authors independently selected papers, assessed risk of bias and extracted data. We resolved disagreements through discussion. We contacted study authors for additional information.

Main results

Three randomised, placebo-controlled trials with a total of 50 participants were included in the review. All the trials were of poor methodological quality and were insufficiently homogeneous to allow the pooling of results. Moreover, the high rate of attrition further increased the risk of bias. None of the trials provided detailed data on the ALS Functional Rating Scale-Revised (ALSFRS-R) scores at six months follow-up which was pre-assigned as our primary outcome. One trial contained data in a suitable form for quantitative analysis of our secondary outcomes. No difference was seen between rTMS and sham rTMS using the ALSFRS-R scores and manual muscle testing (MMT) scores at 12 months follow-up in this trial. Additionally, none of the trials reported any adverse events associated with the use of rTMS. However, in view of the small sample size, the methodological limitations and incomplete outcome data, treatment with rTMS cannot be judged as completely safe.

Authors' conclusions

There is currently insufficient evidence to draw conclusions about the efficacy and safety of rTMS in the treatment of ALS. Further studies may be helpful if their potential benefit is weighed against the impact of participation in a randomised controlled trial on people with ALS.

Plain language summary

Repetitive transcranial magnetic stimulation (rTMS) for treating amyotrophic lateral sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a fatal neurodegenerative disease without significant therapy. People living with this disease become progressively paralysed due to degeneration of the upper and lower motor neurons in the brain and spinal cord. Repetitive transcranial magnetic stimulation (rTMS) has been introduced as a neurophysiological technique and found to have therapeutic activity in several controlled studies on patients with ALS. It is a non-invasive way of stimulating nerve cells in superficial areas of the brain. The technique works through administering pulsed magnetic fields to the surface of the brain at variable frequencies. In this review we identified three studies involving in total 50 participants with ALS. None of the studies reported on the primary outcome, which was disability or limitation in activity as assessed by the ALS Functional Rating Scale-Revised (ALSRFS-R) at six months follow-up. Detailed data on secondary outcomes were only available from 12 participants in one poor quality trial, in which there was no difference between rTMS and sham rTMS in ALSRFS-R or manual muscle testing scores at 12 months follow up. However, rTMS was generally well tolerated by the patients with ALS according to the three included studies; none reported any adverse events associated with the use of rTMS. Considering the small number of patients examined, the flaws in the methods of the three studies and incomplete outcome data, further trials with large sample size and adequate methodology should be considered to determine the efficacy and safety of rTMS in the treatment of ALS, if their potential benefit is weighed against the impact of participation in trials on people with ALS.