The importance of individual beliefs in assessing treatment efficacy.

In recent years, there has been debate about the effectiveness of treatments from different fields, such as neurostimulation, neurofeedback, brain training, and pharmacotherapy. This debate has been fuelled by contradictory and nuanced experimental findings. Notably, the effectiveness of a given treatment is commonly evaluated by comparing the effect of the active treatment versus the placebo on human health and/or behaviour. However, this approach neglects the individual's subjective experience of the type of treatment she or he received in establishing treatment efficacy. Here, we show that individual differences in subjective treatment - the thought of receiving the active or placebo condition during an experiment - can explain variability in outcomes better than the actual treatment. We analysed four independent datasets (N = 387 participants), including clinical patients and healthy adults from different age groups who were exposed to different neurostimulation treatments (transcranial magnetic stimulation: Studies 1 and 2; transcranial direct current stimulation: Studies 3 and 4). Our findings show that the inclusion of subjective treatment can provide a better model fit either alone or in interaction with objective treatment (defined as the condition to which participants are assigned in the experiment). These results demonstrate the significant contribution of subjective experience in explaining the variability of clinical, cognitive, and behavioural outcomes. We advocate for existing and future studies in clinical and non-clinical research to start accounting for participants' subjective beliefs and their interplay with objective treatment when assessing the efficacy of treatments. This approach will be crucial in providing a more accurate estimation of the treatment effect and its source, allowing the development of effective and reproducible interventions.

Neuromodulation is a type of intervention that relies on various non-invasive techniques to temporarily stimulate the brain and nervous system. It can be used for the treatment of depression or other medical conditions, as well as the improvement of cognitive abilities such as attention. However, there is conflicting evidence regarding whether this approach has beneficial effects. Most studies aiming to assess the efficiency of a treatment rely on examining the outcomes of people who received the intervention in comparison to participants who undergo a similar procedure with no therapeutic effect (or placebo). However, the influence of other, 'subjective' factors on these results ­ such as the type of intervention participants think they have received ­ remains poorly investigated. To bridge this gap, Fassi and Hochman et al. used statistical modeling to assess how patients' beliefs about their treatment affected the results of four neuromodulation studies on mind wandering, depression and attention deficit hyperactivity disorder symptoms. In two studies, participants' perceptions of their treatment status were more strongly linked to changes in depression scores and mind-wandering than the actual treatment. Results were more nuanced in the other two studies. In one of them, participants who received the real neuromodulation but believed they received the placebo showed the most improvement in depressive symptoms; in the other study, subjective beliefs and objective treatment both explained changes in inattention symptoms. Taken together, the results by Fassi and Hochman et al. suggest that factoring in patients' subjective beliefs about their treatment may be necessary in studies of neuromodulation and other interventions like virtual reality or neurofeedback, where participants are immersed in cutting-edge research settings and might therefore be more susceptible to develop beliefs about treatment efficacy.

VGLUT2 and APP family: unraveling the neurobiochemical mechanisms of neurostimulation therapy to STZ-induced diabetes and neuropathy.

Diabetic Peripheral Neuropathy (DPN) poses an escalating threat to public health, profoundly impacting well-being and quality of life. Despite its rising prevalence, the pathogenesis of DPN remains enigmatic, and existing clinical interventions fall short of achieving meaningful reversals of the condition. Notably, neurostimulation techniques have shown promising efficacy in alleviating DPN symptoms, underscoring the imperative to elucidate the neurobiochemical mechanisms underlying DPN. This study employs an integrated multi-omics approach to explore DPN and its response to neurostimulation therapy. Our investigation unveiled a distinctive pattern of vesicular glutamate transporter 2 (VGLUT2) expression in DPN, rigorously confirmed through qPCR and Western blot analyses in DPN C57 mouse model induced by intraperitoneal Streptozotocin (STZ) injection. Additionally, combining microarray and qPCR methodologies, we revealed and substantiated variations in the expression of the Amyloid Precursor Protein (APP) family in STZ-induced DPN mice. Analyzing the transcriptomic dataset generated from neurostimulation therapy for DPN, we intricately explored the differential expression patterns of VGLUT2 and APPs. Through correlation analysis, protein-protein interaction predictions, and functional enrichment analyses, we predicted the key biological processes involving VGLUT2 and the APP family in the pathogenesis of DPN and during neurostimulation therapy. This comprehensive study not only advances our understanding of the pathogenesis of DPN but also provides a theoretical foundation for innovative strategies in neurostimulation therapy for DPN. The integration of multi-omics data facilitates a holistic view of the molecular intricacies of DPN, paving the way for more targeted and effective therapeutic interventions.

The promise and challenges of transcranial magnetic stimulation and deep brain stimulation as therapeutic options for obsessive-compulsive disorder.

INTRODUCTION: Obsessive compulsive disorder (OCD) represents a complex and often difficult to treat disorder. Pharmacological and psychotherapeutic interventions are often associated with sub-optimal outcomes, and 40-60% of patients are resistant to first line therapies and thus left with few treatment options. OCD is underpinned by aberrant neurocircuitry within cortical, striatal, and thalamic brain networks. Considering the neurocircuitry impairments that underlie OCD symptomology, neurostimulation therapies provide an opportunity to modulate psychopathology in a personalized manner. Also, by probing pathological neural networks, enhanced understanding of disease states can be obtained. AREAS COVERED: This perspective discusses the clinical efficacy of TMS and DBS therapies, treatment access options, and considerations and challenges in managing patients. Recent scientific progress is discussed, with a focus on neurocircuitry and biopsychosocial aspects. Translational recommendations and suggestions for future research are provided. EXPERT OPINION: There is robust evidence to support TMS and DBS as an efficacious therapy for treatment resistant OCD patients supported by an excellent safety profile and favorable health economic data. Despite a great need for alternative therapies for chronic and severe OCD patients, resistance toward neurostimulation therapies from regulatory bodies and the psychiatric community remains. The authors contend for greater access to TMS and DBS for treatment resistant OCD patients at specialized sites with appropriate clinical resources, particularly considering adjunct and follow-up care. Also, connectome targeting has shown robust predictive ability of symptom improvements and holds potential in advancing personalized neurostimulation therapies.

Stimulation of the pulvinar nucleus of the thalamus in epilepsy: A systematic review and individual patient data (IPD) analysis.

Emerging neuromodulatory treatments, such as deep brain stimulation (DBS) and responsive neurostimulation (RNS), have shown promise in reducing drug-resistant seizures. While centromedian thalamic nucleus and anterior thalamic nucleus stimulation have been effective in certain types of seizures, limited research has explored pulvinar nucleus stimulation for epilepsy. To address this gap, we conducted a systematic review and individual patient data analysis. Of 78 resultant articles, 5 studies with transient stimulation and chronic stimulation of the pulvinar nucleus were included. Of the 20 patients reviewed, 65% of patients had temporal lobe seizures, while 20% had temporooccipital/occipital lobe seizures. Transient stimulation studies via stereoelectroencephalography (SEEG) showed pulvinar evoked potential response rates of 80% in the mesial temporal region, 76% in the temporal neocortex, and 67% in the TP junction. Another study reported clinically less severe seizures in 62.5% of patients with pulvinar stimulation. In chronic stimulation studies, 80% of patients responded to RNS or DBS, and 2 of 4 patients experienced > 90% seizure reduction. The pulvinar nucleus of the thalamus emerges as a potential target for chronic stimulation in drug-resistant epilepsy. However, knowledge regarding pulvinar connectivity and chronic stimulation remains limited. Further research should investigate specific subregions of the pulvinar for epilepsy treatment. Understanding the role of pulvinar stimulation and its cortical connectivity will advance therapeutic interventions for epilepsy patients.

Study on the effect of 40 Hz non-invasive light therapy system. A protocol for a randomized, double-blinded, placebo-controlled clinical trial.

Introduction: With no cure or effective treatment, the prevalence of patients with Alzheimer's disease (AD) is expected to intensify, thereby increasing the social and financial burden on society. Light-based 40 Hz brain stimulation is considered a novel treatment strategy for patients with AD that may alleviate some of this burden. The clinical trial ALZLIGHT will utilize a novel Light Therapy System (LTS). The LTS uses Invisible Spectral Flicker for non-invasive induction of 40 Hz neural activity. This protocol describes a trial evaluating the efficacy and safety of a light-based 40 Hz brain stimulation in patients with mild-to-moderate AD. Methods: 62 patients with mild-to-moderate AD will participate in a randomized, double-blinded, placebo-controlled, parallel-group, and single-center trial. The participants will partake in an enrollment period of 1 month, an intervention period of 6 months, and a 1.5-month post-interventional follow-up period. Prior to the baseline measurement (week 0), the patients will be randomized to either active or placebo intervention from baseline (week 0) to post-intervention follow-up (week 26). Discussion: This protocol describes a randomized, double-blinded, placebo-controlled clinical trial that may increase the understanding of the effect of gamma oscillations in the human brain and how it could be utilized as a novel and important tool for the treatment of AD. The effect is measured through a large, multidisciplinary assessment battery.Clinical trial registration:www.ClinicalTrials.gov, (NCT05260177). Registered on March 2, 2022.

Advancing the frontiers of thalamic neuromodulation: A review of emerging targets and paradigms.

The thalamus is a key structure that plays a crucial role in initiating and propagating seizures. Recent advancements in neuroimaging and neurophysiology have identified the thalamus as a promising target for neuromodulation in drug-resistant epilepsies. This review article presents the latest innovations in thalamic targets and neuromodulation paradigms being explored in pilot or pivotal clinical trials. Multifocal temporal plus or posterior quadrant epilepsies are evaluated with pulvinar thalamus neuromodulation, while centromedian thalamus is explored in generalized epilepsies and Lennox Gastaut syndrome. Multinodal thalamocortical neuromodulation with novel stimulation paradigms such as long bursting or low-frequency stimulation is being investigated to quench the epileptic network excitability. Beyond seizure control, thalamic neuromodulation to restore consciousness is being studied. This review highlights the promising potential of thalamic neuromodulation in epilepsy treatment, offering hope to patients who have not responded to conventional medical therapies. However, it also emphasizes the need for larger randomized controlled trials and personalized stimulation paradigms to improve patient outcomes further.

Neuromodulation for the Sphenopalatine Ganglion-a Narrative Review.

PURPOSE OF REVIEW: To provide an integrated overview of the current state of knowledge of neuromodulation for the sphenopalatine ganglion (SPG) by reviewing relevant and significant literature. RECENT FINDINGS: There are several case reports and clinical trials evaluating neuromodulation for the SPG. We identified two blinded, randomized clinical trials for patients with chronic cluster headache. The randomized trials and additional studies demonstrated the long-term safety, efficacy, and cost-effectiveness of neuromodulation for the SPG. Recent studies in Europe and the USA suggest that SPG neuromodulation is a novel modality with clinical importance for treating acute cluster headaches and reducing the frequency of attacks.

Characteristics of ictal thalamic EEG in pediatric-onset neocortical focal epilepsy.

OBJECTIVE: To characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings. METHODS: Forty habitual seizures were analyzed in nine patients with pediatric-onset neocortical drug-resistant epilepsy who underwent SEEG (age 2-25 y) with thalamic coverage. Both visual and quantitative analysis was used to evaluate ictal EEG signal in the cortex and thalamus. The amplitude and cortico-thalamic latencies of broadband frequencies at ictal onset were measured. RESULTS: Visual analysis demonstrated consistent detection of ictal EEG changes in both the CM nucleus and AN nucleus with latency to thalamic ictal EEG changes of less than 400 ms in 95% of seizures, with low-voltage fast activity being the most common ictal pattern. Quantitative broadband amplitude analysis showed consistent power changes across the frequency bands, corresponding to ictal EEG onset, while while ictal EEG latency was variable from -18.0 seconds to 13.2 seconds. There was no significant difference between detection of CM and AN ictal activity on visual or amplitude analysis. Four patients with subsequent thalamic responsive neurostimulation (RNS) demonstrated ictal EEG changes consistent with SEEG findings. CONCLUSIONS: Ictal EEG changes were consistently seen at the CM and AN of the thalamus during neocortical seizures. SIGNIFICANCE: It may be feasible to use a closed-loop system in the thalamus to detect and modulate seizure activity for neocortical epilepsy.

Novel Insights into the Physiology of Nutrient Sensing and Gut-Brain Communication in Surgical and Experimental Obesity Therapy.

Despite standardized surgical technique and peri-operative care, metabolic outcomes of bariatric surgery are not uniform. Adaptive changes in brain function may play a crucial role in achieving optimal postbariatric weight loss. This review follows the anatomic-physiologic structure of the postbariatric nutrient-gut-brain communication chain through its key stations and provides a concise summary of recent findings in bariatric physiology, with a special focus on the composition of the intestinal milieu, intestinal nutrient sensing, vagal nerve-mediated gastrointestinal satiation signals, circulating hormones and nutrients, as well as descending neural signals from the forebrain. The results of interventional studies using brain or vagal nerve stimulation to induce weight loss are also summarized. Ultimately, suggestions are made for future diagnostic and therapeutic research for the treatment of obesity.

Thalamic responsive neurostimulation for the treatment of refractory epilepsy: an individual patient data meta-analysis.

OBJECTIVE: In recent years, the treatment of drug-resistant epilepsy (DRE) has made greater use of surgery and expanded options for neurostimulation or neuromodulation. Up to this point, responsive neurostimulation (RNS) has been very promising but has mainly used only the cortex as a target. In this individual patient data meta-analysis (IPDMA), the authors sought to establish if a novel RNS target, the thalamus, can be used to treat DRE. METHODS: The literature regarding the management of DRE by targeting the thalamus with RNS was reviewed per IPDMA guidelines. Five databases were searched with keywords [((Responsive neurostimulation) OR (RNS)) AND ((thalamus) OR (thalamic) OR (Deep-seated) OR (Diencephalon) OR (limbic))] in March 2022. RESULTS: The median (interquartile range) age at implantation was 17 (13.5-27.5) years (n = 42) with an epilepsy duration of 12.1 (5.8-15.3) years. In total, 52.4% of patients had previously undergone epilepsy surgery, 28.6% had prior vagus nerve stimulation, and 2.4% had prior RNS. The median preimplant seizure frequency was 12 per week. The median seizure reduction at last follow-up was 73%. No study in this IPDMA reported complications, although 7 cases (16.3%) did require reoperation. Behavioral improvements and reduced antiepileptic drug dose or quantity were reported for 80% and 28.6% of patients, respectively. CONCLUSIONS: This review indicates that thalamic RNS may be safe and effective for treating DRE. Long-term and controlled studies on thalamic RNS for DRE would further elucidate this technique's potential benefits and complications and help guide clinical judgment in the management of DRE.

Multiparametric non-linear TENS modulation to integrate intuitive sensory feedback.

Objective. Transcutaneous electrical nerve stimulation (TENS) has been recently introduced in neurorehabilitation and neuroprosthetics as a promising, non-invasive sensory feedback restoration alternative to implantable neurostimulation. Yet, the adopted stimulation paradigms are typically based on single-parameter modulations (e.g. pulse amplitude (PA), pulse-width (PW) or pulse frequency (PF)). They elicit artificial sensations characterized by a low intensity resolution (e.g. few perceived levels), low naturalness and intuitiveness, hindering the acceptance of this technology. To address these issues, we designed novel multiparametric stimulation paradigms, featuring the simultaneous modulation of multiple parameters, and implemented them in real-time tests of performance when exploited as artificial sensory inputs.Approach. We initially investigated the contribution of PW and PF variations to the perceived sensation magnitude through discrimination tests. Then, we designed three multiparametric stimulation paradigms comparing them with a standard PW linear modulation in terms of evoked sensation naturalness and intensity. The most performant paradigms were then implemented in real-time in a Virtual Reality-TENS platform to assess their ability to provide intuitive somatosensory feedback in a functional task.Main results. Our study highlighted a strong negative correlation between perceived naturalness and intensity: less intense sensations are usually deemed as more similar to natural touch. In addition, we observed that PF and PW changes have a different weight on the perceived sensation intensity. As a result, we adapted the activation charge rate (ACR) equation, proposed for implantable neurostimulation to predict the perceived intensity while co-modulating the PF and charge per pulse, to TENS (ACRT). ACRTallowed to design different multiparametric TENS paradigms with the same absolute perceived intensity. Although not reported as more natural, the multiparametric paradigm, based on sinusoidal PF modulation, resulted being more intuitive and subconsciously integrated than the standard linear one. This allowed subjects to achieve a faster and more accurate functional performance.Significance. Our findings suggest that TENS-based, multiparametric neurostimulation, despite not consciously perceived naturally, can provide integrated and more intuitive somatosensory information, as functionally proved. This could be exploited to design novel encoding strategies able to improve the performance of non-invasive sensory feedback technologies.

Ambulatory Local Field Potential Recordings from the Thalamus in Epilepsy: A Feasibility Study.

INTRODUCTION: Stimulation of the thalamus is gaining favor in the treatment of medically refractory multifocal and generalized epilepsy. Implanted brain stimulators capable of recording ambulatory local field potentials (LFPs) have recently been introduced, but there is little information to guide their use in thalamic stimulation for epilepsy. This study sought to assess the feasibility of chronically recording ambulatory interictal LFP from the thalamus in patients with epilepsy. METHODS: In this pilot study, ambulatory LFP was recorded from patients who underwent sensing-enabled deep brain stimulation (DBS, 2 participants) or responsive neurostimulation (RNS, 3 participants) targeting the anterior nucleus of the thalamus (ANT, 2 electrodes), centromedian nucleus (CM, 7 electrodes), or medial pulvinar (PuM, 1 electrode) for multifocal or generalized epilepsy. Time-domain and frequency-domain LFP was investigated for epileptiform discharges, spectral peaks, circadian variation, and peri-ictal patterns. RESULTS: Thalamic interictal discharges were visible on ambulatory recordings from both DBS and RNS. At-home interictal frequency-domain data could be extracted from both devices. Spectral peaks were noted at 10-15 Hz in CM, 6-11 Hz in ANT, and 19-24 Hz in PuM but varied in prominence and were not visible in all electrodes. In CM, 10-15 Hz power exhibited circadian variation and was attenuated by eye opening. CONCLUSION: Chronic ambulatory recording of thalamic LFP is feasible. Common spectral peaks can be observed but vary between electrodes and across neural states. DBS and RNS devices provide a wealth of complementary data that have the potential to better inform thalamic stimulation for epilepsy.

Peripheral nerve stimulation enables somatosensory feedback while suppressing phantom limb pain in transradial amputees.

To simultaneously treat phantom limb pain (PLP) and restore somatic sensations using peripheral nerve stimulation (PNS), two bilateral transradial amputees were implanted with stimulating electrodes in the proximity of the medial, ulnar and radial nerves. Application of PNS evoked tactile and proprioceptive sensations in the phantom hand. Both patients learned to determine the shape of invisible objects by scanning a computer tablet with a stylus while receiving feedback based on PNS or transcutaneous electrical nerve stimulation (TENS). Оne patient learned to use PNS as feedback from the prosthetic hand that grasped objects of different sizes. PNS abolished PLP completely in one patient and reduced it by 40-70% in the other. We suggest incorporating PNS and/or TENS in active tasks to reduce PLP and restore sensations in amputees.

External trigeminal neurostimulation in patients with chronic migraine.

Aim: To assess the safety and efficacy of external trigeminal neurostimulation (e-TNS) as an add-on treatment in chronic migraine (CM) prophylaxis. Materials & methods: A prospective observational open-label study was conducted on CM patients observed at baseline and 3 months after starting daily sessions of 20 min with e-TNS (Cefaly®). Results: A total of 24 volunteers affected by CM according to the ICHD-3 were included. At the 3 month follow-up, a >30% reduction of headache days was observed in four (16.5%) of 24 patients; a marginal headache improvement was observed in ten (42%) patients, with no or minor adverse effects (four of 24 patients). Conclusion: e-TNS may constitute a safe preventive treatment in CM, its limited efficacy is not statistically significant.

Migraine is one of the most prevalent and disabling diseases in the world. In chronic migraine cases, patients have headache ≥15 days/month, of which at least eight are migraines, for >3 months and often develop a medication overuse headache because of the excessive intake of drugs. Preventive therapies include, among others, peripheral nerve stimulation. In our study, 24 patients affected by chronic migraine were asked to use a peripheral nerve stimulation device (Cefaly^®) for 20 min daily for 3 months. During this period, we evaluated the efficacy and safety of the treatment using specific headache diaries in which patients collect information about their symptoms and disability. Our results show a limited and not statistically significant reduction in headache days in a group of patients ('responders') without serious adverse reactions.

Comparative Effectiveness of Combined and Single Neurostimulation and Traditional Dysphagia Therapies for Post-Stroke Dysphagia: A Network Meta-Analysis.

BACKGROUND: Comparative therapeutic benefits of combined and single neurostimulation therapies including neuromuscular electrical stimulation (NMES), pharyngeal electrical stimulation (PES), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and traditional dysphagia therapy (TDT) remain unknown in post-stroke dysphagia (PSD) rehabilitation. Therefore, we performed the first network meta-analysis (NMA) to determine comparative effectiveness of combined and single neurostimulation and traditional dysphagia therapies for PSD. METHODS: A frequentist NMA model was performed with therapy effect sizes presented as standardized mean differences (SMD) and corresponding 95% confidence interval (95% CI) for therapy comparisons while netrank function ranked the therapies in R-Software. Meta-regression models for study characteristics were analyzed using Bayesian NMA Model. RESULTS: Overall, 50 randomized controlled studies with 2250 participants were included. NMES + TDT 3.82 (95% CI, 1.62-6.01), tDCS + TDT 3.34 (95% CI, 1.09-5.59), rTMS + TDT 3.32 (95% CI, 1.18-5.47), NMES 2.69 (95% CI, 0.44-4.93), and TDT 2.27 (95% CI, 0.12-4.41) demonstrated very large effect in improving swallowing function. NMES + TDT -0.50 (95% CI, -0.68 to -0.32, rTMS + TDT -0.44 (95% CI, -0.67 to -0.21), TDT -0.28 (95% CI, -0.46 to -0.10), and NMES -0.19 (95% CI, -0.34 to -0.04) demonstrated medium to small effect in reducing pharyngeal transit time (PTT). rTMS -0.51 (95% CI, -0.93 to -0.08) demonstrated medium effect in reducing oral transit time (OTT). No significant therapy comparison differences were found for reducing aspiration/penetration. The highest ranked therapy was NMES + TDT for better swallowing function and reduction of PTT, rTMS for reduction of OTT, and tDCS + TDT for reduction of aspiration/penetration. Therapeutic effects of the therapies were moderated by frequency, sessions, and duration. CONCLUSION: Combined therapies including NMES + TDT, tDCS + TDT, and rTMS + TDT demonstrate better therapeutic effect for improved swallowing function and reduction of PTT, OTT, and aspiration/penetration for PSD.

A Pilot Study: The Reduction in Fecal Acetate in Obese Patients after Probiotic Administration and Percutaneous Electrical Neurostimulation.

Previous data suggested that anti-obesity interventions, such as percutaneous electric neurostimulation and probiotics, could reduce body weight and cardiovascular (CV) risk factors by attenuation of microbiota alterations. However, potential mechanisms of action have not been unveiled, and the production of short-chain fatty acids (SCFAs) might be involved in these responses. This pilot study included two groups of class-I obese patients (N = 10, each) who underwent anti-obesity therapy by percutaneous electric neurostimulations (PENS) and a hypocaloric diet (Diet), with/without the administration of the multi-strain probiotic (Lactobacillus plantarum LP115, Lactobacillus acidophilus LA14, and Bifidobacterium breve B3), for ten weeks. Fecal samples were used for SCFA quantification (by HPLC-MS) in relation to microbiota and anthropometric and clinical variables. In these patients, we previously described a further reduction in obesity and CV risk factors (hyperglycemia, dyslipemia) after PENS-Diet+Prob compared to PENS-Diet alone. Herein, we observed that the administration of probiotics decreased fecal acetate concentrations, and this effect may be linked to the enrichment of Prevotella, Bifidobacterium spp., and Akkermansia muciniphila. Additionally, fecal acetate, propionate, and butyrate are associated with each other, suggesting an additional benefit in colonic absorption. In conclusion, probiotics could help anti-obesity interventions by promoting weight loss and reducing CV risk factors. Likely, modification of microbiota and related SCFA, such as acetate, could improve environmental conditions and permeability in the gut.

Wireless Peripheral Nerve Stimulation for The Upper Limb: A Case Report.

Peripheral neuro-stimulation (PNS) has been proved to be effective for the treatment of neuropathic pain as well as other painful conditions. We discuss two approaches to PNS placement in the upper extremity. The first case describes a neuropathic syndrome after the traumatic amputation of the distal phalanx of the fifth digit secondary to a work accident with lack of responsiveness to a triple conservative therapy. An upper arm region approach for the PNS was chosen. The procedure had a favorable outcome; in fact, after one month the pain symptoms were absent (VAS 0) and the pharmacological therapy was suspended. The second case presented a patient affected by progressive CRPS type II in the sensory regions of the ulnar and median nerve in the hand, unresponsive to drug therapy. For this procedure, the PNS device was implanted in the forearm. Unfortunately, in this second case the migration of the catheter affected the effectiveness of the treatment. After examining the two cases in this paper, we changed our practice and suggest the implantation of PNS for radial, median and/or ulnar nerve stimulation in the upper arm region, which has significant advantages over the forearm region.

[Uroflowmetry: A follow-up tool for neurogenic bladder patients treated by transcutaneous tibial posterior stimulation?] / Débitmétrie : outil de suivi chez les patients avec vessie neurologique traités par neurostimulation tibiale postérieure ?

OBJECTIVE: Neurogenic bladders can suffer from overactivity, underactivity or dyssynergia depending on the level of the initial lesion. These symptoms can lead to severe alterations of the upper urinary tract. One of the first-line treatments is the transcutaneous tibial posterior stimulation (TTNS), which was demonstrated to be efficient on urodynamics. But it is an invasive, expensive and sometimes not patient-accepted examination, contrary to the uroflowmetry. The aim of this study is to assess the feasibility of a follow-up with a uroflowmetry when treated by TTNS and show that the maximum flow rate increased after treatment, displaying a better detrusor contraction. METHODS: In total, 38 patients with neurogenic bladder undergoing a 12-weeks TTNS treatment and with 2 uroflowmetries interpretable before and after treatment were included. The maximum flow rate (Qmax), the urinated volume and the post-void residual (PVR) were retrieved from the uroflowmetry, and the USP-score and the urinary discomfort were asked at each appointment. RESULTS: Qmax is increased from 17,53ml/s to 18,26ml/s, as well as the PVR (from 76,97ml to 79,16ml). Urinated volume is decreased from 241,4ml to 193,66ml. Patients feel enhanced after TTNS according to the decrease in the USP-score and the urinary discomfort scale. CONCLUSION: The increase of the cystomanometric capacity and the delay of the detrusor overactivity due to TTNS explains the reduction of the urinated volume and the increase of PVR. Increased Qmax might show a better voluntary bladder contraction, with a restraint due to the lack of abdominal pressure measurement during voiding.

Effect of Neuro-Adaptive Electrostimulation Therapy versus Sham for Refractory Urge Urinary Incontinence Due to Overactive Bladder: A Randomized Single-Blinded Trial.

This randomized clinical trial evaluates the success rate of neuro-adaptive therapy (NAT), applied with a specific neuro-adaptive regulator device, the Self-Controlled Electro Neuro-Adaptive Regulation (SCENAR), versus a sham for urge incontinence due to an overactive bladder (OAB). From February 2019 to May 2021, 66 patients were recruited. All subjects were randomized 1:1 at the first intervention visit to the NAT or sham procedure. Inclusion criteria were females between 18 and 80 years old with leakages due to an overactive bladder with unresponsiveness to medical therapy. Subjects were scheduled to receive up to eight weekly 20 min intervention sessions to obtain a complete (CR) or partial response (PR). Patients with no response after three sessions were considered as a failure. The primary end point of this trial was to assess the efficacy of NAT compared to an inactive sham intervention, evaluated 1 month after the last session. Analysis showed 23 (70%) patients responded (20 complete and 3 partial response) in the NAT group compared to 16 (48%) patients (all complete response) in the placebo arm (p = 0.014). Significant differences were maintained after the intervention, with persistent response at 3 months in 19 (58%) patients after active treatment and 14 (42%) after the placebo (p < 0.001), and at 6 months in 18 (55%) vs. 11 (33%) (p = 0.022), respectively. The number of sessions to achieve CR was similar in both arms, with 4.3 ± 1.9 in NAT and 3.9 ± 1.8 in the sham group (NS). Significant differences were observed between both groups for patients' satisfaction (p = 0.01). The binary model selected age as a predictor of response at the last follow-up. The odds ratio indicates that each year of increase in age, the probability of a positive response to treatment at 6 months decreases 0.95 (95% CI 0.9-0.99) times (p = 0.03). In conclusion, this pilot randomized trial gives evidence that neuro-adaptive electrostimulation is effective to treat refractory urge urinary incontinence due to OAB. The security and long-term efficacy of this treatment merits further evaluation. Moreover, its favorable profile and the economic advantages of the device make the evaluation of this promising technique mandatory in a primary therapeutic scenario.

Clinical and Quality of Life Benefits for End-Stage Workers' Compensation Chronic Pain Claimants following H-Wave® Device Stimulation: A Retrospective Observational Study with Mean 2-Year Follow-Up.

Previously promising short-term H-Wave® device stimulation (HWDS) outcomes prompted this retrospective cohort study of the longer-term effects on legacy workers' compensation chronic pain claimants. A detailed chart-review of 157 consecutive claimants undergoing a 30-day HWDS trial (single pain management practice) from February 2018 to November 2019 compiled data on pain, restoration of function, quality of life (QoL), and polypharmacy reduction into a summary spreadsheet for an independent statistical analysis. Non-beneficial trials in 64 (40.8%) ended HWDS use, while 19 (12.1%) trial success charts lacked adequate data for assessing critical outcomes. Of the 74 final treatment study group charts, missing data points were removed for a statistical analysis. Pain chronicity was 7.8 years with 21.6 ± 12.2 months mean follow-up. Mean pain reduction was 35%, with 89% reporting functional improvement. Opioid consumption decreased in 48.8% of users and 41.5% completely stopped; polypharmacy decreased in 36.8% and 24.4% stopped. Zero adverse events were reported and those who still worked usually continued working. An overall positive experience occurred in 66.2% (p < 0.0001), while longer chronicity portended the risk of trial or treatment failure. Positive outcomes in reducing pain, opioid/polypharmacy, and anxiety/depression, while improving function/QoL, occurred in these challenging chronic pain injury claimants. Level of evidence: III.