Safety and preliminary efficacy of deep transcranial magnetic stimulation in MS-related fatigue

Gunnar Gaede, Marina Tiede, Ina Lorenz, Alexander U Brandt, Caspar Pfueller, Jan Dörr, Judith Bellmann-Strobl, Sophie K Piper, Yiftach Roth, Abraham Zangen, Sven Schippling, Friedemann Paul, Gunnar Gaede, Marina Tiede, Ina Lorenz, Alexander U Brandt, Caspar Pfueller, Jan Dörr, Judith Bellmann-Strobl, Sophie K Piper, Yiftach Roth, Abraham Zangen, Sven Schippling, Friedemann Paul

Abstract

Objective: To conduct a randomized, sham-controlled phase I/IIa study to evaluate the safety and preliminary efficacy of deep brain H-coil repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) and the primary motor cortex (MC) in patients with MS with fatigue or depression (NCT01106365).

Methods: Thirty-three patients with MS were recruited to undergo 18 consecutive rTMS sessions over 6 weeks, followed by follow-up (FU) assessments over 6 weeks. Patients were randomized to receive high-frequency stimulation of the left PFC, MC, or sham stimulation. Primary end point was the safety of stimulation. Preliminary efficacy was assessed based on changes in Fatigue Severity Scale (FSS) and Beck Depression Inventory scores. Randomization allowed only analysis of preliminary efficacy for fatigue.

Results: No serious adverse events were observed. Five patients terminated participation during treatment due to mild side effects. Treatment resulted in a significant median FSS decrease of 1.0 point (95%CI [0.45,1.65]), which was sustained during FU.

Conclusions: H-coil rTMS is safe and well tolerated in patients with MS. The observed sustained reduction in fatigue after subthreshold MC stimulation warrants further investigation.

Clinicaltrialsgov identifier: NCT01106365.

Classification of evidence: This study provides Class III evidence that rTMS of the prefrontal or primary MC is not associated with serious adverse effects, although this study is underpowered to state this with any precision.

Figures

Figure 1. Patient flow diagram
Figure 1. Patient flow diagram
Patient flow in this interventional study. The column on the left side lists the week relative to the first day of intervention. The second column lists the diagnostic parameters assessed at the visits. The column on the right side depicts the patient flow including randomization in the 3 treatment groups. BDI-IA = Beck Depression Inventory IA; EDSS = Expanded Disability Status Scale; FSS = Fatigue Severity Scale; MC = motor cortex; MSFC = Multiple Sclerosis Functional Composite; PFC = prefrontal cortex; rTMS = repetitive transcranial magnetic stimulation.
Figure 2. Changes in fatigue under treatment
Figure 2. Changes in fatigue under treatment
FSS changes during the study using standard boxplots. Treatment group “PFC” is shown in purple, treatment group “MC” in green, and sham group “PFC sham” in gray. Post-treatment visits are termed “follow-up” (plus follow-up visit number). The yellow line indicates FSS cutoff between fatigued (FSS ≥ 4) and nonfatigued values. FSS = Fatigue Severity Scale; MC = motor cortex; PFC = prefrontal cortex.

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Source: PubMed

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