TMS as an Adjunct to Rehabilitation After Stroke: A Potential New Treatment
Abstract & Commentary
By Bruce T. Volpe, MD, Professor of Neurology and Neuroscience, Department of Neurology, Weill Cornell Medical College and the Burke Rehabilitation Hospital. Dr. Volpe reports that he receives grant/research support from Wyeth/ Pfizer.
Synopsis: Transcranial magnetic stimulation was shown to have benefit during stroke rehabilitation therapy, in this randomized, controlled clinical trial.
Source: Khedr EM, Etraby AE, Hemeda M, et. al. Long-term effect of repetitive transcranial magnetic stimulation on motor function recovery after acute ischemic stroke. Acta Neurol Scand, August 2008 (E-pub ahead of print). DOI: 10.1111 / j.1600-0404.2009.01195.x.
This research group, from Assiut, egypt, tested whether the application of repetitive transcranial magnetic stimulation (rTMS) to the skull area over the affected hemisphere would improve motor outcome and reduce disability in patients with stroke. This was an ambitious "pilot study" to generate important information about a number of trial-specific features that includes aspects of a phase 1 study (safety of increasing intensity and frequency of rTMS), a phase 2 study (effectiveness for a specific motor outcome), and a phase 3 study (controlled trial).
The investigators randomly assigned 48 patients with acute ischemic stroke to receive either sham rTMS or rTMS at one of two frequencies (3Hz or 10Hz). Sham rTMS or rTMS was delivered over the affected hemisphere daily for five days. All patients received the same medical treatment (low molecular weight heparin in the first week, then aspirin and piracetam, 2-4g/d, chronically). They also received post-stroke rehabilitation consisting of early passive motion that was later modified to more active treatment. They measured motor performance in the upper and lower limb, the National Institutes of Health (NIH) stroke scale, and the Modified Rankin Scale, before and after treatment and again one month, two months, three months, and 12 months later. Demographics, including age (59.5 ± 13), gender (24M/24F), time from stroke (6.5 ± 3.6), side of lesion (21R/27L), risk factors, and gross estimate of size of infarct, were comparable among the groups. Importantly, the initial motor performance measures were comparable at the start of the study, as measured days after the acute stroke.
TMS required some baseline measures of presumed cortical excitability, and required electromyography (EMG) recording, as typically occurs, from the first dorsal interosseus (FDI) muscle. These measures include resting and active motor threshold (RMT and AMT) and motor evoked potential (MEP).The technique requires optimal scalp localization for the elicitation of a MEP from the FDI in the unaffected, and, if possible, the affected limb. There are also established safety standards for the limits of stimulus intensity as a function of TMS frequency.
There were no untoward complications - particularly, there were no seizures. Electroencephalogram (EG) recordings after the treatment failed to show focal or generalized sharp activity or epileptic activity. Ten dropouts occurred because of a second stroke (4) within the follow up study, or death (2) or other non-medical complications (4). It appeared that the rTMS stimulus characteristics were safe for patients within days of an acute stroke.
The first analysis demonstrated that those treated with real rTMS were better than those treated with sham rTMS on all motor outcome scales, and the improvements persisted during the chronic phase (1-12 mos). The percent improvement in hand grip and shoulder abduction were significantly better for the rTMS treated patients compared to the sham, but the percent improvement in hip and ankle flexion were comparable. Although this is preliminary information, the presumed site of rTMS suggests that the treatment was specific for upper limb motor function.
By one year after stroke, the treated rTMS group also had better NIH stroke scale scores and modified Rankin scores than sham-treated. Improved motor outcome measures and NIH stroke scale were independent of lesion site, but there was an age effect for the NIH stroke scale change that favored the younger patients.
Whether increasing the dose of rTMS generated better scores was not apparent; in fact, the longitudinal study favored the lower frequency treatment (3Hz) at each evaluation time. There were interesting changes in cortical excitability, especially in the unaffected hemisphere of the sham-treated group.
Commentary
These investigators employed the randomized controlled trial to study this group of patients with acute stroke, and they have demonstrated a positive and safe rTMS treatment effect. Much remains to be learned about the fundamental neurophysiology surrounding TMS. (The interested reader is referred to a recent review: Huerta PT, Volpe BT. Transcranial magnetic stimulation, synaptic plasticity and network oscillations. J Neuroeng Rehabil 2009;6:7.)
Whether impairment reduction can be optimized or hastened, and whether impairment reduction will contribute to disability reduction are questions that have stimulated controversy and research. Much of the current regimen in rehabilitation hospitals focuses reasonably, and with moderate success, on disability reduction. It is likely that the combination of bio-engineering (as with robotics and computerized electrical stimulation devices for example) and clinical neurophysiology (TMS as in this study, but, looming on the horizon, transcranial direct current stimulation) will continue to chip away at impairment after stroke. Whether the significant improvements, as in this well-designed study, can generate enough interest to launch a large multi-center study remains to be determined. Rehabilitation centers should be organized into research consortia and, given the low risk for many of the interventions, there should be controlled and randomized studies of new treatments and a concerted effort to generate bio-markers for recovery. When "smart" drugs are ready for common use - molecules that will improve synaptic forms of learning and translate into real world clinical outcomes - such a research infrastructure will then be poised to define rationale for best-treatment plans.
Transcranial magnetic stimulation was shown to have benefit during stroke rehabilitation therapy, in this randomized, controlled clinical trial.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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