Background and Purpose-A sensory-based intervention called peripheral nerve stimulation can enhance outcomes of motor training for stroke survivors with mild-to-moderate hemiparesis. Further research is needed to establish whether this paired intervention can have benefit in cases of severe impairment (almost no active movement). Methods-Subjects with chronic, severe poststroke hemiparesis (n=36) were randomized to receive 10 daily sessions of either active or sham stimulation (2 hours) immediately preceding intensive task-oriented training (4 hours). Upper extremity movement function was assessed using Fugl-Meyer Assessment (primary outcome measure), Wolf Motor Function Test, and Action Research Arm Test at baseline, immediately post intervention and at 1-month follow-up. Results-Statistically significant difference between groups favored the active stimulation group on Fugl-Meyer at postintervention (95% confidence interval [CI], 1.1-6.9; P=0.008) and 1-month follow-up (95% CI, 0.6-8.3; P=0.025), Wolf Motor Function Test at postintervention (95% CI, −0.21 to −0.02; P=0.020), and Action Research Arm Test at postintervention (95% CI, 0.8-7.3; P=0.015) and 1-month follow-up (95% CI, P=0.025). Only the active stimulation condition was associated with (1) statistically significant within-group benefit on all outcomes at 1-month follow-up and (2) improvement exceeding minimal detectable change, as well as minimal clinically significant difference, on ≥1 outcomes at ≥1 time points after intervention. Conclusions-After stroke, active peripheral nerve stimulation paired with intensive task-oriented training can effect significant improvement in severely impaired upper extremity movement function. Further confirmatory studies that consider a larger group, as well as longer follow-up, are needed. Corroborating evidence from a systematic review of randomized and quasi-randomized trials indicated that motor recovery after stroke may be enhanced with PNS, especially when PNS is delivered as an adjunct to motor training. 13,14A well-validated form of motor training called intensive task-oriented training has been associated with significant neuroplastic change, as well as more significant functional gains than usual and customary care, in cases of mild-to-moderate hemiparesis. 15 Further research is needed to optimize intensive task-oriented training for people with severely impaired movement function after stroke. 7 In addition, randomized controlled trials showing that PNS can enhance outcomes of task-oriented training have primarily targeted only mild-to-moderate UE impairment. [16][17][18][19] In sum, although pairing PNS with motor training can enhance motor recovery after stroke, it remains unclear how severity of motor deficit may affect responsiveness to this paired intervention.14 To address these evidence gaps, the purpose of this study was to investigate whether active PNS paired with intensive task-oriented training would lead to significantly more improved movement function than sham PNS paired with intensive ta...

Oral melatonin can improve daytime sleep, but the hormone's short elimination half-life limits its use as a hypnotic in shift workers, jet-lag and other situations. Here we show in healthy subjects that transdermal delivery of melatonin during the daytime can elevate plasma melatonin and reduce waking after sleep onset by promoting sleep in the latter part of an 8-hour sleep opportunity. Thus, transdermal melatonin may have advantages over fast-release oral melatonin in improving sleep maintenance at adverse circadian phases.