Spinal cord stimulation in severe pharmacoresistant restless legs syndrome-two case reports

Abstract

Restless legs syndrome is a prevalent, sleep-related sensorimotor disorder with relevant impact on the patients' quality of life. For patients suffering from severe, pharmacoresistant restless legs syndrome, few therapeutic options remain to alleviate symptoms. In this case series, two patients with severe, pharmacoresistant restless legs syndrome were treated with epidural spinal cord stimulation and repeatedly assessed with polysomnography, including sleep structure and periodic limb movements as objective biomarkers not subject to placebo effects, during a 6-month follow-up period. One of the patients experienced excellent short- and long-term efficacy on subjective symptom severity (International RLS Study group rating scale 1 vs. 34 points at 3 months) and objective sleep parameters such as sleep architecture and periodic limb movements during sleep, while the second patient only reported short-term benefits from spinal cord stimulation. Ultimately, both patients opted for removal of the device for inefficacy. Based on the complex pathophysiology of restless legs syndrome and presumed mechanism of action of spinal cord stimulation in chronic pain disorders, we provide a detailed hypothesis on the possible modulating effect of spinal cord stimulation on the key symptoms of restless legs syndrome. Apart from describing a new therapeutic option for pharmacoresistant restless legs syndrome, our findings might also provide further insights into the pathophysiology of the syndrome.

Keywords: augmentation; case report; epidural spinal cord stimulation; periodic limb movements during sleep; restless legs syndrome.

Figure 1

PSG parameters and sleep structure of patient 2 in the various recording conditions. (A) Table with sleep parameters assessed by PSG. AHI, Apnea-hypopnea index; AI, Arousal-index; C-PAP, Continuous positive airway pressure; LM, Limb movements; IRLS, International RLS Study group rating scale; PLMS, Periodic limb movements during sleep; PMX ER, Pramipexol prolonged release; SE, Sleep efficiency; SL, Sleep latency; Stim, Electro-stimulation; TST, Total sleep time; WASO, Wake after sleep-onset. (B) Comparisons of sleep structure between the different recording conditions. Desat, Blood oxygen level desaturation ≥4%; LM/RRLM, Leg movements/respiratory-related leg movements (also indicated as violet rectangles and bars); N1, N1 sleep; N2, N2 sleep; N3, N3 sleep; R, REM-sleep; and W, Wake.

Figure 2

Polysomnography (PSG) parameters and sleep structure of patient 1 in the various recording conditions. (A) Table with sleep parameters assessed by PSG. AHI, Apnea-hypopnea index; AI, Arousal-index; LM, Limb movements; IRLS, International RLS Study group rating scale; PLMS, Periodic limb movements during sleep; PMX ER, Pramipexol prolonged release; SE, Sleep efficiency; SL, Sleep latency; Stim, Electro-stimulation; TST, Total sleep time; and WASO, Wake after sleep-onset. (B) Comparisons of sleep structure between the different recording conditions. Desat, Blood oxygen level desaturation ≥4%; LM/RRLM, Leg movements/respiratory-related leg movements (also indicated as violet rectangles and bars); N1, N1 sleep; N2, N2 sleep; N3, N3 sleep; R, REM-sleep; and W, wake.

Figure 3

Radiography of patient 1 after definitive implantation confirming the midline position and spinal level of the lead electrodes. (A) Anteroposterior chest and abdominal radiography. (B) Lateral radiography of the thoracic and lumbar spinal column.

Figure 4

Proposed mechanism of action of SCS on the three RLS symptom dimensions on the spinal and supra-spinal level. (A) Direct activation of Aβ sensory fibers as well as inhibitory interneurons in the dorsal horn which exert a gamma-Aminobutyric acid (GABA)-mediated inhibition of wide-dynamic-range neurons and postsynaptic projection neurons carrying peripheral nociceptive signals in the ascending spinothalamic tract. SCS also modulates the activity of cortical and subcortical structures (incl. the basal ganglia and the amygdala), potentially modifying a more general hyperexcitatory network state incl. impaired cortical plasticity described in RLS. (B) Activation of dorsal column axons projecting to the periaqueductal gray, the rostral ventromedial medulla, and locus coeruleus in the midbrain, activate supraspinal inhibitory loops known as the serotoninergic and noradrenergic descending antinociceptive system (DAS). (C) Modulation of the sensory input and restoration of hyperexcitatory local neuronal networks to normal functional levels by SCS might lead to a reduction of local network activity to physiologic levels. Moreover, a direct frequency-dependent activation of opioid receptor subclasses has been described. (D) Increase of segmental dopamine levels via a possible a direct stimulation by SCS of the A11 fibers, mostly located in the dorsolateral funiculus, and thereby causing a dopamine release from the axonal terminals not only directly at stimulation level, but also at caudal levels implicated in motor control of PLM-involved muscle groups. The recruitment of the descending pathways of the DAS (see B) is thought to be, at least in part, the cause of increased spinal 5-HT and GABA and decreased spinal glutamate. A11, Hypothalamic dopaminergic cell group A11; LC, Locus coeruleus; PAG, Periaqueductal gray; and RVM, Rostral ventromedial medulla.