Study on the Efficacy of Spinal Cord Stimulation in Patients With Severe Refractory Primary or Secondary RLS

Restless Legs Syndrome (RLS) is a common chronic sleep disorder characterized by an irresistible urge to move the legs, often accompanied by unpleasant sensations that worsens during rest, particularly at night, and improves with movement. Affecting around 5% of the population, moderate to severe RLS can lead to insomnia, involuntary leg movements during sleep (PLMS), depression, and increased cardiovascular risk, significantly impacting sleep and quality of life and typically requiring long-term treatment.

While the exact cause of RLS is unknown, genetic factors, dopamine system alterations, iron deficiency in the brain, and opioid pathways are suspected contributors. It's mainly classified as primary (unknown cause), with secondary RLS linked to other conditions.

Current first-line treatments involve dopamine agonists (DAs) and alpha-2-delta ligands, which are generally effective but can have long-term limitations. A major issue with DAs is "augmentation," a worsening of RLS symptoms that often leads to treatment discontinuation. DAs are also less effective for insomnia, often requiring combination with sedatives. Opioids are effective but are second-line due to side effects and addiction risk. Importantly, while DAs help with sensory symptoms, they often don't significantly improve sleep quality.

Emerging as a promising non-pharmacological approach is electrical neuromodulation, particularly spinal cord stimulation (SCS). Case studies have shown that SCS can improve RLS symptoms, reduce PLMS, and enhance sleep quality, although long-term efficacy has been variable. The potential mechanism of SCS involves activating sensory fibers and inhibitory interneurons in the spinal cord, influencing pain pathways, and modulating brain regions involved in motor control and sleep regulation. This multilevel action may explain the potential benefits of SCS across the sensory, sleep, and motor aspects of RLS.

SCS, typically used for chronic intractable pain, is being investigated as a potential treatment for severe RLS due to overlapping characteristics between the two conditions. RLS has a sensory component that can include pain, and there's evidence suggesting a link between RLS and chronic pain based on high comorbidity, similar sensory processing abnormalities, the effectiveness of certain medications (opioids and α2δ ligands), and a shared hyperexcitable state in the central nervous system. Notably, some patients receiving SCS for chronic pain have also experienced improvement in their RLS symptoms.

This double-blind randomized controlled crossover study aims at comparing the short-efficacy of SCS with Sham Stimulation, in patients with primary or secondary intractable severe or very severe RLS, with a two-period-alternating treatment design. Burst SCS, a specific spinal cord stimulation waveform that delivers pulses in clusters separated by brief periods without stimulation, is chosen over other modalities due to its demonstrated ability to modulate both the sensory and affective components of pain and discomfort. Unlike traditional tonic stimulation, Burst SCS delivers stimulation patterns that more closely resemble natural neuronal firing, and may provide effective symptom relief without inducing paresthesia. Although specific evidence for RLS is still limited, Burst SCS has shown promising results in related neuropathic conditions and is currently considered one of the most advanced and effective neuromodulation techniques available.

• Treatment response to SCS in % [Срок оценки: From baseline of the treatment phase to end of the 2.5 months treatment phase]
• Change in general health quality of life [Срок оценки: From baseline of the treatment period to the end of the 2.5 months treatment phase]
• Change in RLS-related quality of life [Срок оценки: From baseline of the treatment period to the end of the 2.5 months treatment phase]
• Change of Total Sleep Time (TST), Sleep Latency (SL) and Sleep Efficacy (SE) acquired by actigraphy [Срок оценки: From baseline of the treatment period to the end of the 1 month SCS stimulation during the cross-over of the treatment period]
• Change of PLMS Index recorded by PSG [Срок оценки: From baseline of the treatment period to the end of the 1 month SCS stimulation during the cross-over of the treatment period]
• Difference in RLS symptoms and severity between 1 month of SCS vs. Sham stimulation [Срок оценки: Between 1 month of SCS vs. Sham stimulation]
• Difference in health-related quality of life between 1 month of SCS vs. Sham stimulation [Срок оценки: Between 1 month of SCS vs. Sham stimulation]
• Difference in RLS-related quality of life between 1 month of SCS vs. Sham stimulation [Срок оценки: Between 1 month of SCS vs. Sham stimulation]
• Difference between 1 month of SCS vs. Sham stimulation in TST, SL and SE [Срок оценки: Between 1 month of SCS vs. Sham stimulation]
• Change of sleep parameters recorded by PSG [Срок оценки: From baselene of the treatment period to the end of the 1 month SCS stimulation during the cross-over of the treatment period.]
• Difference between one month of SCS vs. Sham stimulation in PLMS index, TST, SL, SE, number of awakenings and arousal index [Срок оценки: Between 1 month of SCS vs. Sham stimulation]