COPENHAGEN—When applied to the motor cortex, repetitive transcranial magnetic stimulation (rTMS) may ameliorate depression and fatigue related to multiple sclerosis (MS), according to a study presented at the 29th Congress of the European Committee for Treatment and Research in MS (ECTRIMS).
The effects of rTMS may persist for as long as six weeks after the end of stimulation. To a lesser extent, rTMS of the left prefrontal cortex also may reduce depression and fatigue for patients with MS, said Sven Schippling, MD, deputy head of the Neuroimmunology and MS Research Section at University Hospital Zurich.
Results from the study of patients with MS suggest that the technique is safe and well tolerated. The most frequent side effects included headache on the day of or the day after stimulation and paresthesia in the lower or upper limbs.
Technicians Administered Stimulation With an H-Coil
Dr. Schippling and Friedemann Paul, MD, consultant neurologist at Charité University Medical Center in Berlin, administered rTMS with an H-coil that was jointly developed by the Weizmann Institute of Science in Rehovot, Israel, the NIH, and the Jerusalem-based company Brainsway. Compared with the conventional figure-eight coil, the H-coil directly stimulates deeper brain regions (ie, more than 1 cm below the scalp) over a less focused area.
The investigators randomly assigned 28 patients with MS (26 with relapsing-remitting MS and two with secondary progressive MS, female-to-male ratio 4:1, median EDSS 3.0) to rTMS of the motor cortex, rTMS of the left prefrontal cortex, or sham stimulation of the left prefrontal cortex. Patients who received treatment of the motor cortex did not know whether stimulation was real or sham, but technicians and investigators were not blinded for this condition. Rating physicians, who had been blinded to patients’ assignment, recorded clinical ratings and administered questionnaires. Stimulation of the left prefrontal cortex was performed in a double-blinded fashion. After randomization, participants underwent three stimulation sessions per week during a six-week treatment period. Follow-up lasted for six additional weeks and consisted of three biweekly visits.
The researchers assessed fatigue with the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale, and a visual analog scale that the patient completed. Depression was evaluated using the Beck Depression Inventory (BDI) and the 18-item Hamilton Rating Scale for Depression.
Eligible participants were relapse-free for more than 30 days before inclusion and had taken immunomodulatory or immunosuppressant treatment for more than three months before inclusion. To be included, patients had to have an FSS score of 4 or higher or a BDI score of 12 or higher.
Depression Scores Were Not Equally Distributed at Baseline
Approximately one-third of patients had headache on the day of stimulation, and fewer patients had headache on the day after stimulation. Several patients had paresthesia in the lower or upper limbs. Both headache and paresthesia were similar in frequency in the sham and the true stimulation conditions. The investigators observed no severe events in the patients that received true stimulation, and the types and frequency of adverse events were comparable between the three treatment groups.
Baseline BDI scores were not equally distributed between the groups, said Dr. Schippling. Patients who received rTMS of the prefrontal cortex had higher baseline BDI scores, compared with patients who received rTMS of the motor cortex. FSS and BDI scores decreased significantly in patients who received rTMS of the motor cortex. Motor cortex stimulation significantly lowered the rate of fatigue in all the fatigue and depression scores, including the visual analog scale, said Dr. Schippling.
A clear limitation of the study is its small size, said Dr. Schippling. “However, we find the results promising, and we want to embark on a phase II trial because further evidence is needed to draw firm conclusions about what might be an effective treatment. This would be highly desirable, as treatment options in MS-related fatigue are limited,” he concluded.
—Erik Greb
Senior Associate Editor