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Background: Peripheral Nerve Stimulation (PNS) is an established therapy for chronic neuropathic pain of peripheral origin, typically following nerve injury. However, there is a paucity of Randomized Controlled Trials (RCTs) demonstrating the therapeutic benefits of PNS. The goals of the current study (COMFORT Study) are to document the safety and efficacy of the Nalu Neurostimulation in a PNS RCT, compared to conventional medical management (CMM). Methods/Design: This is a prospective, multicenter, RCT evaluating the treatment of neuropathic pain with PNS therapy. One of the following four regions will be targeted for treatment: low back, shoulder, knee or foot/ankle. Consented subjects will undergo a baseline evaluation, after which they are randomized 2:1 (PNS+CMM arm to CMM arm). Subjects randomized to PNS+CMM arm will undergo a trial implant period using best clinical practices. Subjects who pass the trial phase, by showing a ≥ 50% reduction in pain relative to baseline, will receive the permanent implant. All subjects receiving a permanent implant will be followed for a total of 36 months. At the 3-month primary end point, subjects in CMM arm will be given the option to crossover into PNS+CMM arm, beginning with a trial implant. The study duration is expected to be 5.5 years from first enrollment to last follow-up of last subject and subsequent study closure. Adverse events will be captured throughout the study. Discussion: The COMFORT study, described here, has the potential to demonstrate the efficacy and safety of the Nalu Neurostimulation System in the treatment of peripheral neuropathy. Results of this study will be the first Level-I evidence, out to 36 months, validating the use of this PNS system in the treatment of chronic pain. This study is designed to enroll the largest cohort, to date, of subjects comparing PNS+CMM vs CMM alone. Plain Language Summary: Peripheral nerve stimulation (PNS) has been used for decades to treat neuropathic pain of peripheral origin. This therapy typically involves the placement small (~1 mm diameter) cylindrical electrodes (leads) near the nerve(s) in question, which is then followed by the delivery mild electrical pulses to the target, thereby blocking the pain signal from reaching the central nervous system. Despite the clinical success of this approach, there are few randomized controlled trials (RCTs) demonstrating PNS efficacy in the treatment of peripheral neuralgia/neuropathy. This may be, in large part, due to a paucity of PNS devices that are small enough to deliver this therapy at multiple locations in the extremities and the torso. For example, most implantable pulse generators (IPGs) range in size from 14 to 40 cm3 in volume. The purpose of this RCT is to demonstrate the safety and efficacy of an externally powered micro-IPG (< 1.5 cm3 in volume), in the delivery of PNS to treat peripheral neuropathic pain. Active Arm subjects will receive therapy with the micro-IPG and continue to use conventional medical management (CMM); Control Arm subjects will be treated with CMM only. The primary endpoint is the responder rate at 3-months, in both arms, defined as the percentage of subjects with ≥ 50% pain reduction from baseline following implantation of the micro-IPG. Control Arm subjects will be given the option to crossover to the Active Arm at 3-months. Study subjects in both arms are followed out to 36 months. [ABSTRACT FROM AUTHOR]

Case Diagnosis: Hypokalemia induced rhabdomyolysis. Case Description: A 56-year-old male with history significant for transverse myelitis resulting in spastic paraplegia of the lower extremities, and managed with a baclofen pump, presented to the emergency department with a four day history of progressive quadriparesis. Prior level of function included a four-wheeled walker for home mobility and independence of all activities of daily living. Intravenous corticosteroids were initiated due to concern for recurrence of transverse myelitis. Magnetic resonance imaging (MRI), lumbar puncture, and imaging of the baclofen pump were all normal. Laboratory analysis revealed creatine phosphokinase (CPK) was 13821 and serum potassium equal to 1.8. Clinical presentation was consistent with hypokalemia-induced rhabdomyolysis and nephrology consulted. Hypokalemia was multifactorial (laxative use, relative fasting, and vomiting prior to symptom onset) and concurrent spasticity a likely contributor. Potassium was repleted intravenously and stabilized at 3.6. At discharge the patient required moderate to maximum assistance with transfers and toileting and was a candidate for acute inpatient rehabilitation, but elected to discharge with home health. Discussions: Rhabdomyolysis is a pathologic condition of skeletal muscle in which toxic intracellular components are released into the blood stream. These include CPK, alanine aminotransferase, aspartate aminotransferase, myoglobin, and potassium. Local potassium levels impact capillary vascular tension. Low levels of serum potassium lead to capillary vasoconstriction, reduced blood flow to skeletal muscle, relative ischemia, eventual cell death, and lysis. To our knowledge, there have been no reports that address the role of spasticity in development of rhabdomyolysis. By definition, spasticity is velocity-dependent increase in stretch reflexes (muscle tone). It is possible that sustained muscle tone due to spasticity and resulting metabolic demand increases the risk of rhabdomyolysis in the setting of an already ischemic environment resulting from severe hypokalemia. Conclusions: Hypokalemia-induced rhabdomyolysis should be considered as a potential cause of acute weakness in patients with spasticity. [ABSTRACT FROM AUTHOR]