Pagani-Estévez, Gabriel L.

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 Objective Advanced Parkinson's Disease (PD) is associated with Parkinson’s Disease gait impairment (PDg), which increases the risk for falls and is often treatment-refractory. Subthalamic nucleus (STN) and globus pallidus pars interna (GPi) deep brain stimulation (DBS) often fails to improve axial symptoms like PDg. Spinal cord stimulation (SCS) has been suggested to improve PDg. SCS may benefit PDg by disrupting pathologic beta-oscillations and hypersynchrony in cortico-striatal-thalamic circuits to override excessive inhibition of brainstem locomotor regions. SCS may potentially improve locomotion by acting at any of these levels, either alone or in combination. Methods We conducted a comprehensive literature search and scoping review, identifying 106 patients in whom SCS was evaluated for PDg. Results Among the identified patients, 63% carried a pain diagnosis. Overall, the most common stimulation location was thoracic (78%), most commonly T9-T10. Burst (sub-perception) was the most common stimulation modality (59%). Prior treatment with DBS was used in 25%. Motor outcomes were assessed by the Unified Parkinson Disease Rating Scale (UPDRS) III-motor, UPDRS, the Timed Up and Go (TUG), and/or 10-/20-meter walking tests. Among these patients, 95 (90%) had PDg amelioration and improved motor outcomes. Conclusions Despite small sample sizes, patient heterogeneity, and unblinded evaluations complicating interpretations of efficacy and safety, SCS may be beneficial for at least a subset of PDg. Further research is required to clarify the role of SCS for PDg and the patients most suitable to benefit from this intervention.

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)

Abstract Rationale Prostacyclin-associated leg pain is a potentially debilitating adverse effect of prostacyclin therapy for patients with pulmonary arterial hypertension (PAH). However, to our knowledge, this entity has not been systematically studied. Objectives To characterize the clinical features and metabolic risk factors for prostacyclin-associated leg pain. Methods At one academic medical center, we assembled and analyzed a case series of patients with PAH and prostacyclin-associated leg pain. Measurements and Main Results Over a period of 2 years, we identified 11 patients with PAH and prostacyclin-associated leg pain who agreed to participate in this study. Subjects underwent a standardized clinical evaluation, electrodiagnostic assessment, and serologic screen for metabolic causes of peripheral neuropathy. All 11 patients were female; their mean (SD) age was 50 (±9) years; their median (interquartile range) PAH duration was 56 (20–96) months; and their prostacyclin therapy duration was a median (interquartile range) of 20 (14–36) months. All patients reported leg pain beginning soon after prostacyclin initiation and varying with dose. All described a neuropathic pain in a symmetric, distal, stocking distribution. Neurologic examination revealed a sensory, small-fiber, predominantly peripheral neuropathy in seven (78%) patients. Results of autonomic reflex testing and thermoregulatory sweat testing were abnormal in 82% and 90% of patients, respectively, suggesting small-fiber neuropathy. Serologic evaluation identified a new, previously unrecognized contributor to neuropathy in eight (73%) patients, including vitamin B12 deficiency in six (55%), uncompensated hypothyroidism in three (27%), and diabetes mellitus in one (9%). Conclusions Chronic prostacyclin-associated leg pain is associated with a small-fiber neuropathy. Treatable metabolic contributors (vitamin B12 deficiency, thyroid dysfunction, or diabetes) appear to be common possible “second hits” that may be underrecognized. We recommend screening for possible metabolic contributors in patients who have otherwise unexplained leg pain in the setting of PAH and current or anticipated prostacyclin therapy.

Background: Occipital neuromodulation is a promising treatment modality for refractory headache, but lead migration remains a frequent surgical complication. Objectives: The primary objective was to identify surgical techniques that may minimize adverse events, particularly lead migration. We hypothesized that a surgical technique employing 2-point anchoring of stimulator leads designed to provide a tension-relief loop and the use of ultrasound for lead placement would decrease the complication rate. Study Design and Setting: A retrospective analysis was performed through electronic medical record chart review in a tertiary referral center. Methods: Institutional Review Board (IRB) approval was obtained. Eighteen patients had a trial and subsequent permanent occipital nerve stimulator (ONS) implantation between 2004 and 2011 and were included. Adverse events were recorded and efficacy outcome variables analyzed for significance. Results: The cohort was a median (IQR) 45 (37 – 58) in age and 9 (50%) were women. Tension-relief loops placed via a 2-point anchoring technique and ultrasound use for occipital lead placement were evident in 16 (89%) and 13 (72%), respectively. There was one (6%) clinically insignificant lead position change, not definitively a lead migration, which could have been an artifact of fluoroscope positioning. Adverse events included one (6%) battery malfunction, one (6%) lead malfunction, and 2 (12%) post-implantation infections. Following ONS, there were significant reductions in numeric rating scale (NRS) pain scores from a median (IQR) of 9.5 (8.25 – 10) to 2.5 (1 – 4.75) (P < 0.0001), headache days per week from 7 (7 – 7) to 1.5 (0.375 – 1.75) (P = 0.0005), and the number of daily headache medication from 3 (2.25 – 4) to 2.5 (2 – 3.75) (P = 0.0112). Limitations: Limitations include retrospective study design, investigator bias, and nonstandardized intervals of headache burden assessment. Conclusions: In ONS, utilization of a 2-point anchoring technique with a tension-relief loop may significantly minimize the risk of lead migration, based on the absence of definitive lead migration in our series. Ultrasound use may improve the anatomic accuracy of lead placement with the possibility of improved efficacy. ONS was associated with significantly decreased headache pain, frequency, and medication use. Key words: Occipital neuromodulation, occipital nerve stimulation, surgical technique, lead migration, tension-relief loop

Background and objective Epidural blood patch (EBP) is a safe and effective treatment for spontaneous intracranial hypotension (SIH), but clinical and procedural variables that predict EBP efficacy remain nebulous. Methods This study is an institutional review board-approved retrospective case series with dichotomized EBP efficacy defined at 3 months. The study included 202 patients receiving 604 EBPs; iatrogenic cerebrospinal fluid leaks were excluded. Results Of the EBPs, 473 (78%) were single-level, 349 (58%) lumbar, 75 (12%) bilevel, and 56 (9%) multilevel (≥3 levels). Higher volume (OR 1.64; p<0.0001), bilevel (3.17, 1.91–5.27; p<0.0001), and multilevel (117.3, 28.04–490.67; p<0.0001) EBP strategies predicted greater efficacy. Only volume (1.64, 1.47–1.87; p<0.0001) remained significant in multivariate analysis. Site-directed patches were more effective than non-targeted patches (8.35, 0.97–72.1; p=0.033). Lower thoracic plus lumbar was the most successful bilevel strategy, lasting for a median of 74 (3–187) days. Conclusions In this large cohort of EBP in SIH, volume, number of spinal levels injected, and site-directed strategies significantly correlated with greater likelihood of first EBP efficacy. Volume and leak site coverage likely explain the increased efficacy with bilevel and multilevel patches. In patients with cryptogenic leak site, and either moderate disability, negative prognostic brain MRI findings for successful EBP, or failed previous lumbar EBP, a low thoracic plus lumbar bilevel EBP strategy is recommended. Multilevel EBP incorporating transforaminal administration and fibrin glue should be considered in patients refractory to bilevel EBP. An algorithmic approach to treating SIH is proposed.

Intraoperative tourniquet-related pain is well recognized by anesthesiologists, but postoperative tourniquet-related pain has received little attention. We present a patient who underwent a total knee arthroplasty under general anesthesia and an adductor canal nerve block. She complained of intractable thigh pain postoperatively. Lidocaine 5% patches completely resolved her postoperative tourniquet-related pain.