Silber, Michael H.

Abstract Background Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. Objective Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. Methods We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. Discussion The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.

Abstract Introduction Restless legs syndrome (RLS) can dramatically impair sleep quality and quality of life. Some patients have insufficient treatment response or intolerance to available pharmacological options. Exploration of novel therapeutic approaches is needed. Methods We report a case of spinal cord stimulation (SCS) providing benefit in RLS. We also performed a scoping review of SCS in RLS with comprehensive literature search of MEDLINE, EMBASE, Cochrane, and Scopus. Results A 77-year-old woman with DM2, OSA (on ASV), depression, familial RLS and iron deficiency with typical RLS symptoms for all of her adult life presented for management in 2000. In 2011 she developed intractable painful peripheral neuropathy and chronic back pain. Levodopa, pramipexole, oral/intravenous iron, gabapentin, pregabalin, tramadol, oxycodone, and methadone were ineffective or poorly tolerated. A 7-day percutaneous SCS trial resulted in RLS symptoms improvement initially by 50%. A Medtronic stimulator with lead placement at T8-T9 was implanted. 6 months later, the patient toggled between a tonic program (2.1-4.6 mA, 200 us, 50 Hz) and a sub-perception, differential target multiplexed program duty-cycled to 1:2 on:off (3.7 mA, 170 us, 300 Hz). She reported 75% improvement in RLS symptoms. Pain improved by 50%. Total daily dose of Oral Morphine Equivalents was reduced from 48.75mg/day to 37.5mg/day, with a stable once daily dose of 400 mg gabapentin at night. Uninterrupted sleep went from 2-5 hours to 6 hours. RLS worsened when the device was off. Our case corroborates the current evidence of benefit of SCS for RLS from the literature. We identified other 16 unique patients from case reports and series who had undergone SCS for RLS. Leads were most often implanted in mid or low thoracic levels. Stimulation waveforms were high frequency in 4 patients, tonic in 3 patients, burst stimulation in 1 patient, and undescribed in the others. All patients had RLS symptom reduction. Comorbid pain was reported in 14 patients, which also improved with SCS. Complication with lead erosion was reported in one case. Conclusion SCS remains a promising therapeutic approach for refractory RLS that deserves further investigation. SCS may reduce hyperexcitability seen in RLS by modulating dysfunctional spinal, subcortical, and cortical networks. Support (if any)