N-of-1 Trial in Person with Pontine Stroke Receiving Repetitive Transcranial Magnetic Stimulation to Improve Hand Function

Stroke characteristics vary widely between individuals making it difficult to assess the value of stroke rehabilitation interventions. To eliminate inter-subject variability, this study used an N-of-1 randomized, controlled design to explore the efficacy of repetitive transcranial magnetic stimulation (rTMS) in one unique individual with pontine stroke. We hypothesized that five days of active 6-Hz primed, low-frequency rTMS to the contralesional primary motor area (M1), combined with finger movement tracking training, would accomplish greater gains in hand function than sham rTMS combined with tracking training. We assessed hand function (Box and Block test and finger tracking test), cortical activation (laterality index during functional magnetic resonance imaging), and cortical excitability (interhemispheric inhibition testing (IHI) with transcranial magnetic stimulation (TMS)). Diffusion tensor imaging (DTI) assessed the integrity of his corticospinal tracts at baseline. Results showed no improvement in the Box and Block or finger tracking tests, unreliable IHI findings, and no change in laterality index following active rTMS. DTI suggested truncation of the left corticospinal tract (CST) at the pons. His non-dexterous hand movements combined with no elicitable motor evoked potentials with TMS to ipsilesional M1 and his DTI findings lead us to speculate a reticulospinal mechanism for preserving his rudimentary paretic hand control. We conclude that rTMS combined with tracking training was not effective in the absence of CST pathways and that research is needed to confirm markers of reticulospinal function in humans as an alternative to defective CST function.