From Journal Watch
Physician-authored summaries and commentary from the publishers of the New England Journal of Medicine
Journal Watch Neurology
August 21, 2003
Repetitive transcranial magnetic stimulation (rTMS) of the brain is a noninvasive, well-tolerated technique that can modify cerebral cortex excitability both locally and at remote, but functionally connected, areas (Lancet Neurology 2003; 2:145). Initial research on rTMS for motor function in Parkinson disease (PD) showed promising results (Neurology 1994; 44:892), but later research failed to confirm initial findings (e.g., Neurology 1999; 52:768) and has yielded mostly conflicting results. Now, two groups of researchers report results with further variations on rTMS in PD.
Okabe and colleagues randomly assigned 85 medically treated PD patients to one of 3 treatments: rTMS to the motor cortex or occipital cortex (0.2 Hz at 110% of the individual's motor threshold intensity) or sham stimulation. Sham stimulation employed low-intensity electric stimuli to the scalp. Sessions of 100 stimuli each occurred weekly for 8 weeks. Participants' Unified PD Rating Scale (UPDRS) scores improved slightly, but to the same degree in all 3 study groups. The authors conclude that, as applied, rTMS is no better than placebo as add-on treatment for medicated PD patients.
Ikeguchi and colleagues targeted the frontal area at 0.2 Hz and 70% of maximal stimulator output intensity. Twelve patients received 6 rTMS stimulation sessions within 2 weeks, to either the frontal lobes (n=10) or the occipital area (controls, n=6). Three of the patients underwent both frontal and occipital stimulation, separated by at least 1 month. Each session consisted of 60 stimuli. After frontal rTMS, activities of daily living and motor scores of UPDRS showed significant but small improvements compared with baseline. Occipital rTMS failed to induce a clinical benefit. On single photon emission CT (SPECT), frontal and occipital stimulation caused significant reductions in regional cerebral blood flow. However, these SPECT findings were not correlated with clinical improvements, and the analysis used uncorrected statistical thresholds and was done without overlaying onto the patients' brain MRI.
Repetitive TMS might be beneficial for PD that does not respond satisfactorily to medication, but the conflicting results to date do not provide a clear answer. The parameters of stimulation and the cortical target are critical, a point underscored by previous studies of frontal rTMS (e.g., Mov Disord 2002; 17:528). Studies in animals (Neuropharmacology 2002; 43:101) and healthy humans (J Neurosci 2001; 21:RC157) show that focal rTMS to the frontal cortex can induce dopaminergic release in the striatum. Larger studies are important, but good control conditions are essential. PD patients are particularly sensitive to placebo effects due to abnormal dopamine-dependent reward mechanisms (Trends Neurosci 2002; 25:302), and a better sham-rTMS method will be crucial.
Most important, we still know little about the mechanisms of action of rTMS, how to control for differences between individuals in rTMS effects on cortical excitability, and how to choose suitable stimulation parameters (e.g., frequency of rTMS, intensity, number of stimuli per session, number of sessions per week, length of stimulation course). Many of these questions must be answered before a proper clinical trial can be designed.
— Felipe Fregni, MD, and Alvaro Pascual-Leone, MD, PhD
Dr. Fregni is Research Fellow in Neurology, Laboratory for Magnetic Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston. Dr. Pascual-Leone is Associate Professor Neurology, Laboratory for Magnetic Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston.
Okabe S et al. for the Effectiveness of rTMS on Parkinson's Disease Study Group. 0.2-Hz repetitive transcranial magnetic stimulation has no add-on effects as compared to a realistic sham stimulation in Parkinson's disease. Mov Disord 2003 Apr; 18:382-8.
Ikeguchi M et al. Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease. J Neurol Sci 2003 May 15; 209:41-6.