Jennifer Myunghae Hah

Peripheral nerve stimulation (PNS) has evolved substantially over recent decades in terms of hardware and evidence supporting efficacy. Treatment targets continue to expand and address both pain and functional applications. The American Society of Pain and Neuroscience (ASPN) seeks to substantially update and expand upon a review of the evidence supporting PNS as well as provide guidelines for clinical practice. A diverse multidisciplinary panel of experts was selected to provide opinions and guidance based on evidence-graded assessment and clinical knowledge. This document aims to serve as a resource for clinicians and payors in the interest of expanding awareness of the breadth of research in the field of PNS and expanding access to therapy.

Objective: Preoperative opioid misuse is associated with worse postoperative outcomes. This prospective longitudinal cohort study evaluated the association between preoperative opioid misuse and prolonged pain and opioid use after elective spine surgery; and examined postoperative trajectories of patient-reported outcomes over one year.Methods: Fifty-two patients undergoing elective spine surgery completed presurgical and weekly postoperative longitudinal assessments of pain and opioid use and monthly assessments of depression, anxiety, sleep disturbance, and physical function. Cox regression analyzed the effect of preoperative opioid misuse on time to pain and opioid cessation while linear mixed-effects models examined longitudinal changes in postoperative outcomes.Results: Adjusting for age, sex, operative region, number of spinal levels, and any preoperative opioid use, preoperative opioid misuse (COMM-Positive) was associated with a delayed return to baseline opioid dose (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.14–0.88; p=0.02) and delayed opioid cessation (HR, 0.25; 95% CI, 0.09–0.59; p=0.008). All patients experienced comparable reductions in current and average pain intensity, and pain interference over time. COMM-Positive patients reported a normalization of postoperative anxiety and depression 1 month after surgery with a rebound at 3 months while patients without preoperative opioid misuse remained stable over time.Conclusion: Preoperative opioid misuse is a significant risk factor for delayed opioid cessation even after adjusting for preoperative opioid use, and is associated with a transient normalization of anxiety and depressive symptoms with a rebound 3 months following spine surgery. Targeted screening and risk reduction strategies are needed for patients reporting preoperative opioid misuse before spine surgery.

We aimed to evaluate real-world outcomes of peripheral nerve stimulation (PNS) used to treat chronic neuropathic pain (CNP) at a tertiary pain management center. Thirty adults who underwent PNS for CNP between June 2015 and September 2021 completed pain and psychosocial assessments in the 6 months before, and 2-3 years after PNS treatment. Pain intensity was measured using the NIH Patient Reported Outcomes Measurement Information System (PROMIS) Pain Intensity Short From (3A). Psychosocial outcomes including depression, anxiety, and sleep disturbance were also measured. Prior to receiving PNS, long-term responders reported significantly fewer depressive symptoms compared to non-responders (PROMIS depression t-score 50.3 [10.7] vs 57.9 [8.9]; p-value = 0.05). Eleven participants (36.7%) reported long-term treatment response. There was a significantly greater improvement in pain intensity among responders compared to non-responders who reported increased pain (PROMIS Pain Intensity score -9.0 [-4.2] vs. +3.1[+3.2]; p-value < 0.0001). Patients report clinically meaningful long-term pain relief after receiving PNS through both 60-day and permanent implant systems, with significant reductions in pain intensity observed in long-term responders. Long-term responders reported fewer depressive symptoms compared to non-responders prior to receiving therapy, emphasizing the importance of psychological screening and psychological optimization prior to receiving PNS.

Importance The opioid epidemic continues to grow, and while the adverse effects of opioids are well–known, their impact on short-term mortality in patients with dementia or mild cognitive impairment (MCI) remains understudied, despite the high vulnerability of this population. Objective To evaluate the short-term mortality risk associated with initiating opioids in patients diagnosed with dementia or MCI Design Retrospective observational cohort study Setting Multisite healthcare system in Northern California Participants Health records of 27,759 patients aged 50–100 with dementia or MCI, with encounters between January 1, 2015, and July 31, 2024. Exclusions included patients who died within 14 days of surgery, had fewer than three clinical encounters before and after diagnosis, or were first diagnosed with dementia/MCI at death. Exposures Initial opioid use following dementia or MCI onset. Patients were categorized as new users (no opioid use in the prior year) or consistent users (prior opioid exposure). Main Outcome and Measures Short–term mortality risk, defined as death within 14 days of first opioid exposure, with additional monitoring up to 60 days after opioid initiation. Hazard ratios were calculated using Cox proportional hazards regression, adjusting for demographics, comorbidities, and medication exposure. We used GPT.3.5–Turbo to identify possible causes of death from unstructured clinical documentation, supplemented by data from California public death records. Results Among 14,107 patients prescribed opioids following the onset of dementia/MCI onset, 9444 were new users and 4663 were consistent users. The cohort was predominantly female (56.0%), with a median age of 81 years (IQR:73–87). New users exhibited a 1.95–fold (95% CI, 1.55 – 2.46; P < 0.0001) increased risk of mortality within 14 days of initial opioid exposure compared to consistent users. Respiratory illnesses were more prevalent among new users who died within 14 days after opioid exposure (62% vs. 48%, PConclusion Opioid initiation in patients with dementia or MCI is linked to significantly higher short–term mortality, particularly in those with respiratory conditions. These findings highlight the need for cautious prescribing and close monitoring, given the increased mortality risk.

Background There is paucity of data from randomized controlled trials supporting the use of peripheral nerve stimulation, a well-established therapy for the treatment of chronic pain. This study was undertaken, in part, to provide randomized controlled trial data in support of patient access to appropriate peripheral nerve stimulation therapy. The COMFORT study is the first large, postmarket, multicenter randomized controlled trials investigating the use of a Food and Drug Administration-cleared micro-implantable pulse generator (IPG) for treating chronic pain via peripheral nerve stimulation therapy. Methods Consented, eligible subjects were randomized to either the active arm, which received peripheral nerve stimulation and conventional medical management, or the control arm, which received conventional medical management alone and were allowed to cross over to the active arm, after 3 months. Pain and patient-reported outcomes were captured. Therapy responders were subjects who achieved at least a 50% reduction in pain scores compared with baseline. We are reporting the 12-month results of this 36-month study. Results At 12 months, the responder rate was 87% with a 69% average reduction in pain compared with baseline (7.5±1.2 to 2.3±1.7; pConclusions These 12-month results are consistent with previously reported 6-month outcomes from this study, showing durability of peripheral nerve stimulation treatment with the micro-IPG system; subjects realized sustained large reduction in pain and improvement in patient-reported outcomes following treatment with this micro-IPG system. Trial registration number NCT05287373.

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.

Spinal CSF leaks lead to spontaneous intracranial hypotension (SIH). While International Classification of Headache Disorders, Third Edition (ICHD-3) criteria necessitate imaging confirmation or low opening pressure (OP) for SIH diagnosis, their sensitivity may be limited. We offered epidural blood patches (EBPs) to patients with symptoms suggestive of SIH, with and without a documented low OP or confirmed leak on imaging. This study evaluates the efficacy of this strategy. We conducted a prospective cohort study with a nested case-control design including all patients who presented to a tertiary headache clinic with clinical symptoms of SIH who completed study measures both before and after receiving an EBP between August 2016 and November 2018. The mean duration of symptoms was 8.7 ± 8.1 years. Of 85 patients assessed, 69 did not meet ICHD-3 criteria for SIH. At an average of 521 days after the initial EBP, this ICHD-3-negative subgroup experienced significant improvements in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical Health score of +3.3 (95% CI 1.5-5.1), PROMIS Global Mental Health score of +1.8 (95% CI 0.0-3.5), Headache Impact Test (HIT)-6 head pain score of -3.8 (95% CI -5.7 to -1.8), Neck Disability Index of -4.8 (95% CI -9.0 to -0.6) and PROMIS Fatigue of -2.3 (95% CI -4.1 to -0.6). Fifty-four percent of ICHD-3-negative patients achieved clinically meaningful improvements in PROMIS Global Physical Health and 45% in HIT-6 scores. Pain relief following lying flat prior to treatment was strongly associated with sustained clinically meaningful improvement in global physical health at an average of 521 days (odds ratio 1.39, 95% CI 1.1-1.79; p < 0.003). ICHD-3-positive patients showed high rates of response and previously unreported, treatable levels of fatigue and cognitive deficits. Patients who did not conform to the ICHD-3 criteria for SIH showed moderate rates of sustained, clinically meaningful improvements in global physical health, global mental health, neck pain, fatigue, and head pain after EBP therapy. Pre-treatment improvement in head pain when flat was associated with later, sustained improvement after EBP therapy among patients who did not meet the ICHD-3 criteria. This study provides Class IV evidence that epidural blood patch is an effective treatment of suspected CSF leak not conforming to ICHD-3 criteria for SIH.

This review focuses on the challenges of diagnosing and treating spontaneous intracranial hypotension (SIH), a condition caused by spinal CSF leakage. It emphasizes the need for increased awareness and advocates for early and thoughtful use of empirical epidural blood patches (EBPs) in suspected cases. SIH diagnosis is hindered by variable symptoms and inconsistent imaging results, including normal brain MRI and unreliable spinal opening pressures. It is crucial to consider SIH in differential diagnoses, especially in patients with connective tissue disorders. Early EBP intervention is shown to improve outcomes. SIH remains underdiagnosed and undertreated, requiring heightened awareness and understanding. This review promotes proactive EBP use in managing suspected SIH and calls for continued research to advance diagnostic and treatment methods, emphasizing the need for innovative imaging techniques for accurate diagnosis and timely intervention.

Background: Opioids are commonly prescribed for postoperative pain, but may lead to prolonged use and addiction. Diabetes impairs nerve function, complicates pain management, and makes opioid prescribing particularly challenging. Methods: This retrospective observational study included a cohort of postoperative patients from a multisite academic health system to assess the relationship between diabetes, pain, and prolonged opioid use (POU), 2008–2019. POU was defined as a new opioid prescription 3–6 months after discharge. The odds that a patient had POU was assessed using multivariate logistic regression controlling for patient factors (e.g., demographic and clinical factors, as well as prior pain and opiate use). Findings: A total of 43,654 patients were included, 12.4% with diabetes. Patients with diabetes had higher preoperative pain scores (2.1 vs 1.9, p<0.001) and lower opioid naïve rates (58.7% vs 68.6%, p<0.001). Following surgery, patients with diabetes had higher rates of POU (17.7% vs 12.7%, p<0.001) despite receiving similar opioid prescriptions at discharge. Patients with Type I diabetes were more likely to have POU compared to other patients (Odds Ratio [OR]: 2.22; 95% Confidence Interval [CI]:1.69–2.90 and OR:1.44, CI: 1.33–1.56, respectively). Interpretation: In conclusion, surgical patients with diabetes are at increased risk for POU even after controlling for likely covariates, yet they receive similar postoperative opiate therapy. The results suggest a more tailored approach to diabetic postoperative pain management is warranted.