Background Epidural neuromodulation platforms include spinal cord stimulation (SCS) and dorsal root ganglion (DRG) stimulation. Condition-specific approvals exist across both platforms for adult patients, with expanding indications lacking a comprehensive analysis of the clinical data. We conducted a comprehensive evidence appraisal of SCS and DRG stimulation for indication-specific chronic pain conditions and to generate stratified recommendations informed by the quality, strength, and certainty of evidence. Materials and Methods The North American Neuromodulation Society (NANS) convened an Epidural Stimulation Guideline Development Group (GDG) consisting of multidisciplinary expert panelists from its membership with conflict-of-interest governance and oversight from the Guidelines Oversight Committee (GOC). A systematic literature search of Ovid MEDLINE®, Embase, Cochrane CENTRAL, and Scopus was conducted through July 1, 2025. Eligible studies evaluated epidural SCS or DRG for chronic pain from persistent spinal pain syndrome type I (PSPS I), painful diabetic neuropathy (PDN), length-dependent peripheral neuropathy (LDPN), spinal cord injury or insult (SCI), central post-stroke pain (CPSP), fibromyalgia, and multiple sclerosis (MS). The primary outcome was pain reduction, with multiple secondary outcomes reported related to quality of life and improved function. Evidence was graded using United States Preventive Services Task Force (USPSTF) recommendation grades and levels of certainty and agreed upon by modified Delphi consensus approach. Results Recommendation strength and level of certainty varied by indication. Grade A recommendations were assigned to SCS for PSPS I and PDN. Grade C recommendations were assigned to SCS for LDPN, SCI, CPSP, and DRG stimulation for PDN. Evidence was absent, insufficient, or suggested small net benefit for SCS for fibromyalgia and MS. Evidence was absent for DRG for PSPS I, SCI, CPSP, fibromyalgia and MS. There were no Grade B recommendations. Functional and quality of life outcomes were inconsistently reported across studies. Variation in study methods, clinical syndromes, device parameters, and reporting structure all limit the reliability of data and the certainty of recommendations. Conclusions These guidelines provide indication-specific epidural stimulation recommendations to aid decision-making for clinicians and payors. Epidural stimulation platforms for emerging diagnoses are increasingly offered to patients, with these guidelines supporting these strategies for patients with refractory pain due to PSPS I, PDN, LDPN, SCI, and CPSP. SCS for MS may have limited benefit. Future research supporting epidural stimulation for specific indications will benefit from homogenous minimal data sets, randomized clinical trials, patient-reported outcomes, and long-term follow-up.
Objectives To characterize the effect of deep brain stimulation (DBS) on restless legs syndrome (RLS) severity using the International RLS Study Group Rating Scale (IRLS), and to test whether this benefit reflects direct neuromodulation or the indirect reduction in dopaminergic medication. Materials and Methods PubMed/MEDLINE, Embase and Scopus were searched for studies reporting quantitative RLS outcomes in adults undergoing DBS for any indication. The primary outcome was change in IRLS score (0–40); secondary outcomes were levodopa equivalent dose (LEq), de novo stimulation-induced RLS, responder rate, and polysomnographic parameters. Estimates were pooled as weighted mean differences (WMD) by sample size, with pre-specified subgroups by target and indication. Weighted least-squares regression tested the association between LEq reduction and IRLS improvement. Results Eighteen studies comprising 875 patients were included; ten (N = 479) provided extractable pre- and post-DBS IRLS scores. The pooled WMD was −9.6 points (51.8% reduction). Patients with PD undergoing STN-DBS (k = 7, N = 464) improved by −9.7 points. Studies accounting for approximately 78% of patients reported mean IRLS reductions of ≥50%. Three studies reported de novo stimulation-induced RLS in 18 of 227 patients (7.9%), exclusively with STN-DBS. Ten studies (N = 745) reported a weighted mean LEq reduction of 549.0 mg/day (58%). Regression of IRLS improvement on LEq reduction (k = 6) yielded a slope of +0.0006 (95% CI −0.030 to +0.031; R2 = 0.001) with an intercept of 9.8 points. Conclusions DBS is associated with a clinically meaningful reduction in RLS severity. The absence of any association between LEq reduction and IRLS improvement and an intercept at zero medication change matching the observed benefit support direct neuromodulation rather than dopaminergic withdrawal as the principal mechanism. Approximately 7.9% of patients develop paradoxical stimulation-induced RLS. These data support prospective investigation of DBS for drug-refractory primary RLS.
Introduction Long COVID is a multisystemic condition in which olfactory disorders are among the most prevalent manifestations. Non-invasive Neuromodulation has emerged as a promising therapeutic approach for post-COVID sequelae. This systematic review and Bayesian meta-analysis aimed to synthesize the available evidence on neuromodulation for olfactory improvement in Long COVID patients. Materials and Methods A systematic search was conducted in PubMed/MEDLINE, Embase, and Cochrane Library from inception through January 22, 2026, in accordance with PRISMA 2020 guidelines. Studies were eligible if they included Long COVID patients undergoing any non-invasive neuromodulation modality for olfactory disturbances and had a control group. Risk of bias was assessed using Cochrane Risk of Bias 2 tool (RoB 2) for randomized controlled trials (RCTs) and the Risk of Bias in Non-Randomized Studies of Interventions tool (ROBINS-I) for non-randomized intervention studies (NRIS). A Bayesian random-effects meta-analysis was performed using the brms package in R, with risk ratios (RR) and 95% credible intervals (CrI) as effect measures. Results Four studies were included, employing heterogeneous neuromodulation modalities. The pooled RR for complete olfactory recovery (normosmia) was 1.59 (95% CrI: 0.41–6.28), with a 73.9% posterior probability of benefit (RR > 1); however, the credible interval included the null. For clinically meaningful olfactory improvement, the pooled RR was 2.20 (95% CrI: 0.63–7.52), with an 88.8% posterior probability of benefit, though the interval marginally included the null. Sensitivity analyses using wider priors yielded substantially different estimates, indicating prior dependence of the results. No serious adverse events were reported across studies. Conclusions The available evidence suggests a possible favorable direction of effect of non-invasive neuromodulation on olfactory dysfunction in Long COVID, but certainty is very low. These findings should be interpreted as hypothesis-generating. Larger trials using standardized olfactory testing and pre-specified stimulation protocols are warranted before any clinical recommendation can be made.
Background Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of upper and lower motor neurons driven by dysregulated excitability, impaired proteostasis, and pathological protein aggregation. Optimizing neuromodulation strategies that effectively target spinal motor circuits may help attenuate functional decline in ALS. Multi-site direct current stimulation (DCS) is designed to distribute current across spinal networks and may provide more robust modulation than conventional trans-spinal configurations. Materials and Methods In an initial electrophysiological experiment, corticospinal-evoked muscle contractions were recorded using a force-displacement transducer to compare the effects of different multi-site spinal electrode configurations on corticospinal output. Subsequently, two ALS mouse models, SOD1ˆG93A and TDP-43ˆA315T, underwent repeated in vivo multi-site anodal DCS. Motor function was assessed using grid walking, hindlimb grip strength, and wire-hang tests across five time points. In the TDP-43ˆA315T model, motor neuron soma size was quantified using choline acetyltransferase (ChAT) immunostaining, while HSP70 expression and TDP-43/p-TDP-43 aggregation were evaluated using Western blotting and confocal imaging. Results Multi-site DCS produced the strongest suppression of corticospinal-evoked muscle contractions among all electrode configurations tested, indicating robust modulation of spinal excitability. In SOD1ˆG93A mice, repeated stimulation preserved motor performance across all behavioral assays, with the clearest differences emerging during later disease stages relative to unstimulated controls. In TDP-43ˆA315T mice, stimulation was associated with improved motor performance at the final testing point and with preservation of motor neuron soma size. In this model, stimulation also increased HSP70 expression and was associated with reduced accumulation of pathological phosphorylated TDP-43, consistent with enhanced proteostatic capacity. Conclusion Multi-site anodal DCS effectively modulates spinal excitability and preserves motor function in two mechanistically distinct mouse models of ALS. In the TDP-43ˆA315T model, these functional benefits are accompanied by preservation of motor neuron structure and molecular changes consistent with improved protein homeostasis. Together, these findings support multi-site DCS as a promising neuromodulatory strategy for influencing disease-relevant mechanisms and slowing functional decline in ALS.
Background Stroke is a leading cause of long-term disability, with upper-limb impairment being common and debilitating. Vagus nerve stimulation (VNS) is a promising therapy to improve neuroplasticity and motor recovery post-stroke. However, comparative evidence for invasive VNS (iVNS) and transcutaneous VNS (taVNS) is limited. We conducted a systematic review and meta-analysis to assess their efficacy and safety for upper-limb rehabilitation. Materials and Methods A systematic literature search of PubMed, Embase, and Scopus was performed. Randomized controlled trials evaluating VNS paired with rehabilitation in adult patients with ischemic or hemorrhagic stroke were included. The primary outcome was upper-limb motor recovery assessed using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE). Secondary outcomes included the Wolf Motor Function Test (WMFT), Modified Barthel Index (MBI), and adverse events. Results Eleven randomized controlled trials comprising 402 patients were included. VNS was associated with significant improvement in FMA-UE scores compared with control groups (MD 4.45, 95% CI 2.49-6.40; p < 0.00001), although substantial heterogeneity was observed (I2 = 93%). Sensitivity analysis demonstrated persistent treatment effects with markedly reduced heterogeneity (MD 2.73, 95% CI 1.99-3.48; I2 = 4%). Significant improvements were also observed for WMFT (MD 1.40, 95% CI 0.56-2.25) and MBI (MD 6.57, 95% CI 2.02-11.11). Subgroup analyses demonstrated significant benefits for both invasive and transcutaneous VNS compared with their respective control groups, with no statistically significant differences between subgroup estimates. However, these findings should not be interpreted as evidence of equivalence between delivery modalities because no direct head-to-head comparisons were available. Overall adverse-event risk did not significantly differ between VNS and control groups (OR 2.52, 95% CI 0.85–7.48). However, device-related adverse events demonstrated a borderline increase among VNS-treated patients (OR 2.35, 95% CI 1.01–5.46), although this estimate was based on relatively few events. Most taVNS-related adverse events were mild and transient, whereas iVNS studies demonstrated procedure-related complications including pain, bruising, hoarseness, and vocal cord paresis. Conclusion VNS combined with rehabilitation significantly improves post-stroke upper-limb recovery. Both invasive and transcutaneous methods are effective, but taVNS is more scalable and less invasive since it avoids surgery and device procedures. More multicenter trials are necessary to determine the long-term efficacy, safety, and best clinical use of VNS in stroke rehab.
Objectives Anesthesia dolorosa (AD) is a rare and debilitating deafferentation pain syndrome that can occur following injury to the trigeminal system, often after procedures for trigeminal neuralgia. Management remains challenging, with limited high-quality evidence and no consensus regarding optimal treatment. This narrative review evaluates procedural strategies for trigeminal AD and AD-spectrum trigeminal deafferentation pain. Materials and Methods We performed a narrative literature review of procedural approaches for trigeminal AD and AD-spectrum trigeminal deafferentation pain with no date or language restrictions. Articles were grouped by anatomical and mechanistic intervention category, including motor cortex stimulation (MCS) and somatosensory cortex stimulation, deep brain stimulation, thalamic stimulation and lesioning, nucleus caudalis/dorsal root entry zone (DREZ) and trigeminal nucleotomy procedures, trigeminal/sphenopalatine ganglion interventions, spinal/cervicomedullary stimulation and other approaches. Results A total of 54 studies were included. The literature was dominated by retrospective case series and case reports, with substantial heterogeneity in patient selection, procedural technique, outcome definitions, and follow-up duration. MCS and deep brain stimulation demonstrated benefit in some patients, but responses were inconsistent and durability varied. Thalamic lesioning, nucleus caudalis procedures and peripheral or ganglion-targeted interventions produced mixed results, with variable response rates and procedure-specific morbidity. Cross-study synthesis was limited by inconsistent reporting and a lack of standardized pain and functional outcome measures. Conclusions Evidence for procedural treatment of trigeminal AD remains low quality and heterogeneous. Reversible neuromodulatory approaches may benefit selected patients, but durability and predictors of response remain uncertain. Ablative procedures produced analgesic responses in small, selected reports but require cautious interpretation because of irreversibility, limited evidence and target-site morbidity. Larger multicenter datasets with standardized diagnostic definitions and outcome reporting are required.
Objectives Our previous prospective, international multicenter study, the EChO Study, confirmed the common clinical observation that when deactivating spinal cord stimulation (SCS) treatment, there is a variable interval before the patient perceives return of the pain, a phenomenon often termed the carryover effect.When SCS treatment is resumed, there is also a time interval before the treatment effect is restored again; the latency.This follow-up study to the EChO study aimed to investigate and quantify the latency effect and assess correlations with the carryover effect and with clinical and treatment parameters. Materials and Methods Eligible patients with a beneficial effect of their SCS treatment were instructed to deactivate their SCS device in a home setting, to reactivate it when their pain returned, and to record the time when the pain-relieving treatment effect was reinstated.Correlation between carryover and latency were investigated using linear regression. Association with central clinical parameters (age, sex, indication for SCS, SCS treatment details, pain score) was analyzed for latency using non-parametric tests (Mann-Whitney / Kruskal-Wallis) for categorical data and linear regression for continuous data. Results 151 patients were included in the analysis. A median latency of 3.5 hours was found (interquartile range 1;12.2). Only back pain as indication (n=19) and 10kHz stimulation (n=13) were correlated with longer latency. Conclusions This study confirms the existence of the latency effect and demonstrates a lower median and lower degree of inter-individual variation than was the case for carryover effect.The analyses suggest that rather than being a mirror aspect of the carryover effect, the latency effect could likely be considered a different physiological phenomenon.The results emphasize the importance of accounting for the latency effect in clinical practice and in designing clinical trials.
Background/Aims Diabetes mellitus is a prevalent chronic condition globally. A frequent complication is gastric motility disorder, which substantially impacts patients' quality of life and overall well-being. The SMC-ICC-PDGFRα+ (SIP) syncytium plays an important role in the coordination of gastrointestinal (GI) motility. Auricular vagus nerve stimulation (aVNS) has demonstrated promising therapeutic efficacy against diabetic motility disorders, yet the underlying mechanism has not been well understood. The present study aims to evaluate whether low-frequency aVNS attenuates gastric dysmotility in diabetic rats through regulation of the SIP syncytium and its signaling pathways. Materials and Methods Male Sprague-Dawley rats were employed to induce the diabetic gastric motility disorder (DGMD) model using streptozotocin (STZ). The DGMD rats underwent treatment with aVNS, a combination of aVNS and body electroacupuncture (aVNS-EA), and sham aVNS. Gastric motility was evaluated by solid gastric emptying rate (SGER). Gastric antrum pathology was assessed via H&E staining, SIP syncytium function was evaluated by immunofluorescence, and serum nitric oxide (NO) levels with a Griess kit. Results Low-frequency aVNS significantly enhanced SGER and up-regulated the expression of ICCs and PDGFRα+ cells in the antrum, the smooth muscle marker α-SMA was increased at the immunofluorescence and mRNA levels but not significantly at the protein level. aVNS-EA exhibited similar effects, whereas sham aVNS showed no significant change. aVNS also up-regulated nNOS, increased NO release, and activated the sGC–cGMP–PKG1 pathway. Treatment with ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), the sGC inhibitor, reversed the aVNS-induced improvements in SGER and SIP syncytium integrity. Conclusion In contrast, aVNS-EA benefits were only partially inhibited by ODQ. These results suggest that low-frequency aVNS improves gastric motility and SIP syncytium function in diabetic rats by activating the NO/sGC/cGMP/PKG1 pathway, and the combination of aVNS and body electroacupuncture yields additional beneficial effects. Clinical trial registration Not applicable.
Objectives Timely and thorough investigation of intrathecal baclofen (ITB) pump system malfunction is essential for optimal spasticity management. We reviewed 7 years of investigation data to determine the value of radio-opaque catheter dye studies (RCDS) in confirming suspected ITB pump system malfunction. Materials and Methods A retrospective review of electronic medical records was conducted for patients admitted under the author’s spasticity service for ITB pump system investigation or catheter revision surgery between January 2018 and December 2024 (7-year period). Demographic data, investigation results and ITB dose at various stages were collected and compared. Results In the ITB cohort of 188 patients, 41 patients experienced at least one suspected ITB system malfunction (49 admissions). There were 5 admissions where investigations were not performed, all of which proceeded to catheter revision based on strong clinical suspicion of catheter malfunction. Catheter access port (CAP) procedures were completed in 44 admissions; in 9 of these it was not possible to aspirate, and all 9 proceeded directly to catheter revision. Of the 35 successful CAP procedures, twenty-two proceeded to RCDS, only one was positive and went directly to catheter revision surgery. Thirteen of the 21 admissions with a negative RCDS underwent lumbar puncture (LP) boluses, eight of which demonstrated superior effect to pump boluses suggesting catheter malfunction. Of the 8 admissions of negative RCDS without LP, four went on to have catheter revision due to a clear history of fluctuating spasticity.In total 31 of 49 admissions investigated showed evidence of catheter malfunction, 27 proceeded to theatre for revision surgery. Conclusion Radio-opaque catheter dye studies showed a high false negative rate and provided low value in identifying ITB pump system malfunction. Instead, careful clinical assessment, early CAP procedure and consideration of pump ITB bolus with or without a comparison LP bolus is more valuable and effective.
Background Neuromodulation includes a spectrum of therapeutic interventions that have transformed the management of neurological and psychiatric conditions globally. Africa bears a disproportionate burden of neurological disease yet remains underrepresented in neuromodulation research and clinical practice. This review aimed to synthesize the available evidence on neuromodulation practice and research across African health systems, identify key barriers and opportunities, and propose future directions to expand equitable access. Materials and Methods A literature search was conducted across PubMed, Scopus, Web of Science, Embase, and African Journals Online (AJOL) from inception to March 2026, combining neuromodulation modality terms with African country and regional identifiers. A narrative synthesis approach was adopted, organized thematically by modality and supplemented by analysis of barriers, opportunities, and future directions. Results Electroconvulsive therapy (ECT) is the most practiced neuromodulation modality in Africa, but is delivered inconsistently, with unmodified ECT still practiced in some countries due to resource constraints. Deep brain stimulation (DBS) programs exist in only four to five countries, principally Algeria, Egypt, Morocco, South Africa, and Tunisia, and serve a minute fraction of eligible patients. Evidence for the use of transcranial magnetic stimulation (TMS) in Africa is sparse and largely confined to North and Southern Africa. Transcranial direct current stimulation (tDCS), despite its suitability for low-resource settings, is almost absent from African literature. Vagus nerve stimulation (VNS), spinal cord stimulation (SCS), and peripheral nerve stimulation are undocumented across the continent. African populations are excluded from global neuromodulation clinical trials. Barriers identified include severe neurological workforce shortages, prohibitive costs of devices and procedures, inadequate infrastructure, the absence of national regulatory frameworks, cultural stigma, and systemic underrepresentation in research. Opportunities include piloting tDCS as a practical, low-cost option pending African-specific feasibility and efficacy data; telemedicine-enabled remote neuromodulation delivery; deliberate inclusion of African sites in international trials; carefully governed task-sharing with allied health workers; and development of regional centers of excellence. Conclusion Neuromodulation remains largely absent from the published record on African health systems, despite the continent's growing burden of neurological disease. This reflects the available evidence rather than a definitive absence of clinical practice. Addressing this equity gap requires sustained investment in African-led research, workforce development, regulatory frameworks, and international research partnerships.
OBJECTIVES:To evaluate the analgesic effect of four weeks home-based transcranial direct current stimulation (tDCS) compared with low-intensity sham stimulation in individuals with type 1 diabetes mellitus and painful diabetic peripheral neuropathy. MATERIALS AND METHODS:A total of 35 participants with type 1 diabetes mellitus and painful diabetic peripheral neuropathy were enrolled in a home-based, randomized, double-blind, sham-controlled, crossover study. Each participant underwent four weeks of active (2 mA) and sham (0.3 mA) tDCS in a randomized order. Clinical and experimental end points were assessed before and after each treatment. The primary end point was pain relief, measured daily using a numeric rating scale. Secondary end points included various questionnaires. Quantitative sensory testing was used to assess the pain system. RESULTS:No significant differences in pain scores were observed after four weeks of active tDCS compared with sham (mean difference in average pain 0.03 (95% CI, -0.40 to 0.46; p = 0.89, mean difference in maximal pain 0.09 (95% CI, -0.42 to 0.60; p = 0.73). However, active tDCS reduced pain compared with baseline: Average pain (p = 0.026) and maximum pain (p = 0.012), unlike sham tDCS. However, taking all four weeks of treatment into consideration, sham tDCS reduced pain scores (p < 0.05). No differences were found between the treatments for the secondary outcomes. Responders to active tDCS showed increased temporal summation and lower pressure pain thresholds. CONCLUSIONS:Active tDCS significantly reduced pain compared with baseline but did not show an improvement over low-intensity sham tDCS. Responders to active tDCS exhibited features of central sensitization. Stimulation intensity may influence tDCS effectiveness. CLINICAL TRIAL REGISTRATION:The clinicaltrial.gov registration number for the study is NCT06152887.
Background Tremor and freezing of gait (FOG) are two disabling symptoms that may defy currently available medical or stimulation therapies in some patients with Parkinson’s disease (PD). Objective To evaluate the effects of anodic stimulation in treatment-resistant FOG and tremors in PD patients undergoing STN DBS. Materials and Methods Five PD patients, four with treatment-refractory FOG and one with recurrent tremor, following bilateral STN-DBS were systematically assessed under both cathodic and anodic stimulation, with all other stimulation parameters held constant to isolate polarity-dependent effects. Results Compared with conventional cathodic stimulation, anodic stimulation was associated with clinically meaningful improvement in FOG and tremor in this selected cohort. Conclusion Anodic stimulation (AS) may offer an alternative programming strategy for resistant FOG and tremor cases. The findings need to be further confirmed by mechanistic and longitudinal studies integrating imaging, neurophysiology, and computational modeling to optimize individualized therapy.
BACKGROUND:Transcutaneous spinal cord stimulation (tSCS) has been shown to be an effective enhancement for upper extremity (UE) motor recovery when paired with upper extremity activity-based rehabilitation training (UE ABRT) for those with cervical spinal cord injury (cSCI). Factors suggested to contribute to the effectiveness tSCS include parameters of stimulation and participant characteristics. This review aimed to identify stimulation parameters linked to enhanced neurophysiological engagement and functional recovery. Additionally, this review also considered how participant characteristics influenced the effectiveness of tSCS-based rehabilitation. MATERIALS AND METHODS:A systematic search was conducted for studies up to September 2025 in the following databases: Ovid MEDLINE, Ovid Embase, Web of Science, Cochrane Library, and CINAHL. Two reviewers independently screened the studies and evaluated the quality of the studies using the Modified Downs and Black Checklist. Participant characteristics, injury profile, stimulation parameters, and study design were extracted. RESULTS:A total of 3619 articles were initially screened, of which 38 met the inclusion criteria. Fourteen studies included only an able-bodied (AB) population, 19 studies included people with cSCI only, and five studies investigated the effects of tSCS in both AB and SCI participants. The mean quality of the studies was poor (11.82 ± 2.18: Modified Downs and Black Checklist score; scores <15 classified as poor quality). Although some stimulation parameters remained consistent among most studies (frequency: 30 Hz, pulse width: 1 ms, carrier frequency: 5-10 kHz), many of these parameters had no neurophysiological justification. Additionally, parameters such as electrode configuration and intensity of stimulation were highly variable. The studies included participants across a wide age range, and the articles focused on individuals with traumatic and chronic injuries. CONCLUSIONS:There is a lack of mechanistic understanding of how tSCS parameters can influence neurophysiological engagement. There are notable gaps in the literature regarding how participant characteristics, such as age or injury chronicity, affect the efficacy of tSCS and the selection of optimal stimulation parameters. Many studies failed to provide adequate justification for their chosen parameters, limiting the ability to assess their effectiveness.
OBJECTIVES:In this retrospective study, we evaluated high-frequency spinal cord stimulation (SCS) as an alternative neuromodulation strategy for patients with medically intractable chronic cluster headache (MICCH) in whom occipital nerve stimulation (ONS) had failed. BACKGROUND:MICCH represents a severe and treatment-resistant form of cluster headache, for which preventive pharmacologic treatment options are limited. ONS is increasingly used as a peripheral neuromodulation strategy for MICCH, but a subset of patients remains refractory despite treatment. Cervical SCS could be a central neuromodulation strategy for these patients. MATERIALS AND METHODS:This retrospective study included 14 patients with MICCH (nine female, five male; mean age 47 years) who were treated with high cervical 10 kHz SCS after ONS failure. Clinical data were collected on attack frequency, attack duration, intensity of attacks, and quality of life throughout the duration of neuromodulation treatment. RESULTS:Mean SCS follow up duration is 33 ± 21 months. At the last SCS follow-up, ten of 14 patients had a lower mean attack frequency compared with their last ONS assessment (64 ± 33 vs 36 ± 34 weekly attacks, p = 0.02). At the last SCS follow-up six patients obtained a reduction in attack frequency relative to baseline. Mean attack duration decreased from 110 ± 86 to 88 ± 56 minutes, whereas attack intensity remained unchanged. Quality-of-life outcomes were inconsistent and did not uniformly correspond with clinical improvement. CONCLUSIONS:High cervical 10 kHz SCS may represent a feasible rescue neuromodulation strategy for patients with MICCH unresponsive to ONS, with a subset achieving sustained reductions in attack frequency. Interpretation of the effects of SCS on attack duration and pain intensity is limited due to missing data. Nevertheless, these findings support its potential as a treatment option in this highly resistant population. Well-controlled prospective studies are needed to confirm efficacy and further define the role of SCS in treatment algorithms. CLINICAL TRIAL REGISTRATION:This study was not registered as a clinical trial it is a retrospective observational cohort study. The intervention was offered as a last-resort treatment within regular clinical care to patients with medically intractable chronic cluster headache and was therefore not prospectively designed or conducted as a trial.
BACKGROUND:Noninvasive transcranial alternating current stimulation (tACS) of the cochlea might be a promising new therapeutic option for patients with chronic tinnitus. However, electric stimulation of small, sensitive target regions, such as the inner ear, can cause adverse side effects (SEs). OBJECTIVE:The objective of this study was to identify stimulation parameters with low SE profiles while reliably stimulating the cochlea, thereby improving patient comfort and safety. This pilot study also aims to identify stimulation settings suited for developing a medical device intended to treat patients with chronic tinnitus. APPROACH:Participants with healthy hearing were stimulated with electrodes in the ear canal. Stimulation of the cochlea elicits a soft hearing impression (HI) in participants, indicating successful stimulation of the auditory pathway. We systematically compare HIs and SEs across distinct electrode configurations and stimulation parameters, including stimulation frequency and the presence of a direct current (DC)-offset. We record SE severity ratings through visual analog scales after stimulation. PRIMARY RESULTS:We find that tACS between 250 Hz and 2000 Hz reliably elicits HIs in participants. SE severity depends on the stimulation parameters. No magnitude of SEs caused participant withdrawal or severe adverse events, with only phosphenes, skin tingling, and a sense of vibration being reported as impactful. The addition of a slight DC-offset increases the magnitude of phosphenes but does not alter HI occurrence. SIGNIFICANCE:Our results show the feasibility of tACS to stimulate the auditory pathway noninvasively with minimal adverse SEs. Stimulation parameters with a low SE profile can be applied in further studies with patients with tinnitus. CLINICAL TRIAL REGISTRATION:This study was preregistered at the German Register of Clinical Studies (DRKS, https://drks.de/search/de/trial/DRKS00033120).
OBJECTIVES:This study aimed to describe clinical outcomes, dosing, and safety of intrathecal baclofen (ITB) therapy in patients with medically refractory stiff person syndrome (SPS). MATERIALS AND METHODS:We retrospectively reviewed six patients with predominantly anti-glutamic acid decarboxylase (GAD)-positive SPS who underwent ITB pump implantation after inadequate response or intolerance to oral antispasticity medications and immunomodulatory therapies. Clinical features, prior treatments, ITB dosing, complications, and functional outcomes were analyzed. RESULTS:All the patients had severe stiffness and stimulus-sensitive spasms refractory to benzodiazepines, oral baclofen, and immunotherapy. Indications for ITB included respiratory compromise (n = 2), recurrent hip dislocations (n = 2), severe functional impairment (n = 6), and medication intolerance (n = 3). Maintenance ITB doses ranged from 365 to 650 μg/d. All patients experienced substantial reductions in stiffness and spasm frequency, with improved mobility or respiratory function. In one patient, postoperative septic shock developed, requiring temporary device removal; no long-term device failures occurred. Clinical benefit was sustained for 2.5 to four years of follow-up. DISCUSSION:ITB therapy may provide durable symptomatic improvement in severe, medically refractory SPS and should be considered in appropriately selected patients.
BACKGROUND:Spinal Cord Stimulation (SCS) is a therapeutic option for chronic pain conditions, such as persistent spinal pain syndrome, complex regional pain syndrome, painful diabetic peripheral neuropathy, and radiculopathy. The treatment typically involves a temporary trial phase before permanent implantation. Despite showing efficacy, trial phase failure and long-term SCS outcomes remain important considerations. The aim of this review was to quantify three key SCS outcomes-(1) trial phase nonresponse, (2) annual explantation rates after permanent implantation up to three years, and (3) annual <50% pain reduction rates among patients who retain their implant up to three years. MATERIALS AND METHODS:A systematic literature review was conducted across PubMed, Embase, and Cochrane data bases to identify studies reporting on SCS outcomes. Studies were included if they reported quantitative data on at least one of the three outcomes. Data were extracted and summarized across studies. A three-level binomial generalized linear mixed model with logit link was used to calculate pooled rates across included studies. Risk of bias was assessed using the Risk of Bias 2 tool and National Institutes of Health quality assessment tools as appropriate, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation framework. RESULTS:A total of 38 studies were included in the analysis. The pooled trial phase failure rate was 16.2%. Pooled explant rates were 4.0%, 7.0%, and 11.9% at one, two, and three years respectively. Pooled rates of <50% pain reduction were 24.2%, 27.0%, and 32.8% at one, two, and three years respectively. CONCLUSIONS:We aggregate and analyze the durability of SCS outcomes according to a defined rubric. Outcomes were not stratified by factors that could influence response, such as waveform. 16.2% of patients assessed for SCS eligibility did not proceed past the trial phase. On average, at three years post implantation, 44.7% of patients with permanent implants had undergone explantation or reported <50% pain relief.
BACKGROUND:Peripheral magnetic stimulation therapy (PMST) has emerged as a promising, noninvasive alternative to the traditional treatment approaches for urinary incontinence (UI). This systematic umbrella review aimed to synthesize the available secondary literature to provide a definitive, high-level overview of PMST's efficacy, safety parameters, and clinical utility. MATERIALS AND METHODS:A systematic overview was conducted following the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. An a priori protocol was registered via the International Prospective Register of Systematic Reviews (PROSPERO), and systematic literature screening was performed using Rayyan. The Joanna Briggs Institute critical appraisal checklist was utilized to evaluate the methodological quality of the included systematic reviews and meta-analyses. Primary study overlap across the portfolio was structurally mapped and mathematically quantified using the Corrected Covered Area (CCA) formula. The certainty of the synthesized evidence across key clinical end points was evaluated using the narrative GRADE framework. Data extraction was restricted strictly to the systematic review components. RESULTS:Fifteen systematic reviews and meta-analyses were included. Citation matrix analysis revealed a Corrected Covered Area (CCA) of 3.64%, demonstrating a slight overlap and confirming that the synthesized secondary evidence base is non-redundant. Synthesized data revealed a consistent frequency-specific pattern across the included reviews, whereby higher-frequency protocols (35-50 Hz) were most commonly applied to pelvic floor muscle recruitment in stress urinary incontinence, whereas lower-frequency protocols (10-15 Hz) were more frequently used for urgency urinary incontinence and overactive bladder. However, these observations represent prevailing treatment approaches rather than a validated therapeutic paradigm. Relative to sham/placebo configurations, PMST yielded statistically and clinically significant improvements in objective leakage metrics (pad tests) and subjective symptom indices (ICIQ-SF, Health-Related Quality of Life). Safety data demonstrated a remarkable tolerability profile, with adverse events limited to mild, transient, and self-limiting symptoms (eg, local tingling, mild soreness, or increased stool frequency), with no severe complications reported. Methodological quality across the evidence base was highly polarized, with 25% of reviews scoring high and the remainder classified as moderate or low due to deficits in comprehensive database search strings or formal primary study risk-of-bias monitoring. CONCLUSION:PMST appears to be a safe and potentially effective therapeutic option for the management of urinary incontinence and may be considered either as a standalone treatment or as an adjunct to conventional physical therapy. However, the interpretation and clinical application of these findings are limited by considerable heterogeneity in stimulation protocols, patient populations, and outcome measures; variable methodological quality among the included reviews; and the scarcity of long-term follow-up data exceeding six months.
OBJECTIVES:Auricular percutaneous electrical nerve field stimulation (PENFS) is a Food and Drug Administration-approved treatment for functional abdominal pain associated with irritable bowel syndrome and functional dyspepsia. Because PENFS is relatively new, insurance coverage has been inconsistent, with patients experiencing denials or delays in authorization. Thus, we aimed to evaluate insurance authorizations and their influence on outcomes in children with disorders of gut-brain interaction (DGBI) who undergo PENFS. MATERIALS AND METHODS:We reviewed charts of patients with DGBI aged seven to 21 years receiving PENFS at the DGBI Clinic at Cincinnati Children's Hospital from 2017 to 2024. We computed the duration of insurance authorization steps to treatment, divided the cohort into early and delayed authorization groups, and assessed outcomes on the basis of collected validated questionnaire scores. RESULTS:Among 309 patients (median age 15 years; 78% female; 90% Caucasian), 75% had private and 25% public insurance. Prior authorization (PA) was not required in 55% of cases, whereas 18% were initially approved and 27% denied. Overall, 70% of patients were approved and 30% were denied after completion of the insurance process. Private insurers were more likely to deny PA than public ones (29% vs 21%, p = 0.003). Kaplan-Meier analysis showed significantly longer time to approval for those denied coverage (p < 0.001). Outcomes based on validated questionnaire scores did not differ between early and delayed insurance groups at the final PENFS placement visit (p > 0.05 for all). CONCLUSION:Private insurance denials are significantly more common than public, creating disparity in availability of PENFS treatment for this group of patients with complex conditions. The timing of insurance denials can lead to delayed treatment, providing less than optimal patient care.
Objectives Weight loss is a common manifestation of Parkinson's disease (PD) associated with frailty, morbidity, and mortality. Deep brain stimulation (DBS) often leads to significant postoperative weight gain, which confers a survival benefit. This weight gain has traditionally been attributed to reduced energy expenditure from improved hyperkinetic motor symptoms. We aimed to critically examine the evidence for this hyperkinetic hypothesis and explore alternative mechanisms. Materials and Methods We performed a structured narrative review of the MEDLINE/PubMed and Embase databases (from inception through December 2025), identifying English-language abstracts and clinical studies examining the relationship between motor symptom improvement and postoperative weight changes following DBS in PD. Results Correlations between weight gain and improvements in tremor, rigidity, or dyskinesia are inconsistent and often absent, particularly when confounders are controlled. Converging evidence supports alternative mechanisms involving altered resting and total energy expenditure, neuroendocrine dysregulation, and neuromodulation of hypothalamic and limbic circuits influencing appetite and metabolism. Conclusions The hyperkinetic hypothesis alone does not explain post-DBS weight gain. A broader, systems-level framework integrating motor, metabolic, and neuroendocrine pathways is needed to guide future research and inform therapeutic strategies for addressing weight loss in PD.
