UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
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.

Guillain-Barré syndrome (GBS) is a neurological disorder characterized by peripheral, autoimmune-mediated demyelinating polyneuropathy, which can cause muscle weakness and paralysis. While most cases are triggered by respiratory or gastrointestinal infections, vaccinations have also been linked to GBS pathogenesis. The association of the influenza vaccine and GBS, notably prevalent during the 1976 United States swine flu pandemic, has significantly decreased with contemporary seasonal influenza vaccines. At the same time, cases of GBS have been reported with newer vaccines, like the recently approved respiratory syncytial virus (RSV) vaccines. However, their exact relationship with autoimmune demyelinating polyneuropathy remains unknown. In this report, we present a case of a 60-year-old man who developed GBS two weeks after receiving the new Pfizer\'s RSV vaccine in conjunction with the influenza vaccine for the first time.

The abducens nerve, which is vulnerable because of its complex anatomy at the skull base, is seldom affected by acute or severe sphenoid sinusitis. Notably, abducens nerve palsy following asymptomatic chronic rhinosinusitis (CRS) in a healthy young individual after a mild upper respiratory infection (URI) remains undocumented in the literature. Herein, we report a case of acute unilateral abducens neuropathy in a healthy 35-year-old woman with CRS in the ipsilateral sphenoid sinus, following a mild URI 2 weeks earlier. She presented with sudden-onset diplopia, was afebrile, and had normal serum inflammatory biomarkers. Comprehensive ophthalmological and neurological exams revealed no abnormalities except limited lateral gaze in the left eye. Imaging revealed mucosal swelling on the hyperpneumatized left sphenoid sinus, which thinned the clivus and positioned the inflamed mucosa close to the Dorello\'s canal, likely facilitating the spread of inflammation to the ipsilateral abducens nerve. Urgent endoscopic sinus surgery combined with systemic corticosteroids and antibiotics led to complete resolution by postoperative day 10. The present case demonstrates acute abducens nerve neuropathy from URI-induced exacerbation of sphenoid sinus CRS with specific anatomical predispositions.

UNASSIGNED: Contraceptive implant migration is a rare complication associated with contraceptive implants: migration to the ulnar nerve, emphasizing the importance of accurate diagnosis, imaging, and a multidisciplinary approach to mitigate neurovascular risks during insertion and removal procedures. The case report demonstrates the necessity for careful removal techniques and thorough patient follow-up to ensure positive outcomes and prevent long-term nerve damage.
There are some potential risks and complications associated with contraceptive implants, including neurovascular injury. The aim of this case report is to report a rare complication associated with contraceptive implants. A 32-year-old female, right-hand dominant, presented to the orthopedic clinic for the extraction of a contraceptive implant (Implanon) from her left arm. She reported intermittent numbness in the ring and little fingers. Upon examination, the Implanon was not palpable. Both Phalen\'s test and Tinel signs were negative. An x-ray of the arm revealed the implant\'s position. Under local anesthesia through a longitudinal incision, the Implanon was found within the perineurium of the ulnar nerve. Two weeks after the operation, the patient returned to the clinic. Upon examination, there were no indications of ulnar nerve neuropathy. If a patient undergoes subdermal implant-associated pain or is at risk of neurovascular damage during removal, it is advisable to refer the patient to a family planning specialist experienced in handling challenging implant removals, and subsequently to a peripheral nerve surgeon, to optimize outcomes. The migration of a contraceptive implant to the ulnar nerve is an exceedingly rare but possible complication.

Introduction: Pathogenic variants in the XK gene are associated with dysfunction or loss of XK protein leading to McLeod syndrome (MLS), a rare X-linked neuroacanthocytosis syndrome with multisystemic manifestation. Here we present clinical, genetic and immunological data on a patient originally admitted to our clinic for presumed post-COVID-19 syndrome, where thorough clinical work-up revealed a novel frameshift deletion in XK causal for the underlying phenotype. We additionally review the clinicogenetic spectrum of reported McLeod cases in the literature. Methods: We performed in-depth clinical characterization and flow cytometry of cerebrospinal fluid (CSF) in a patient where multi-gene panel sequencing identified a novel hemizygous frameshift deletion in XK. Additionally, Kell (K) and Cellano (k) antigen expression was analysed by Fluorescence-activated Cell Sorting (FACS). KEL gene expression was examined by RNA sequencing. Results: A novel hemizygous frameshift deletion in the XK gene resulting in premature termination of the amino acid chain was identified in a 46-year old male presenting with decrease in physical performance and persisting fatigue after COVID-19 infection. Examinations showed raised creatine kinase (CK) levels, neuropathy and clinical features of myopathy. FACS revealed the K-k+ blood type and reduced Cellano density. CSF flow cytometry showed elevation of activated T Cells. Conclusion: In-depth clinical, genetic, immunological and ribonucleic acid (RNA) expression data revealed axonal neuropathy, myopathy and raised levels of activated CSF-T-lymphocytes in a patient with a previously unpublished frameshift deletion in the XK gene.

Mind-body therapies have been found to be effective in a variety of pathologies. The purpose of this study was to evaluate the efficacy of meditation-based therapies in relieving the symptoms severity, quality of life, stress and other associated mood conditions, in individuals with chronic neuropathy of various etiologies. A systematic review of randomized controlled trials, involving adult patients with persistent peripheral neuropathy, was performed. Seven article databases were searched. A meta-analysis was conducted to assess the benefits of meditation-based therapy on symptomatology, quality of life, anxiety, depression, perceived stress, sleep quality and mindfulness score. Ten of the 1133 reviewed papers were selected for quantitative review. The meditation group had a lower standardized mean difference (SMD) score (-0.47 (95% CI: -0.97 to 0.02), p=0.062) for neuropathic pain severity score; lower anxiety scores (-2.5 (95% CI: -3.68 to -1.32), p=<0.001); lower depression scores (-1.53 (95% CI: -2.12 to -0.93), p=<0.001); lower perceived stress (-1.06 (95% CI: -3.15 to 1.04), p=0.323); higher quality of life scores (2.19 (95% CI: -0.65 to 5.03), p=0.13); lower sleep quality scores (-1.27 (95% CI: -4.22 to 1.67), p=0.397); higher mindfulness scores (6.71 (95% CI: 4.09 to 9.33), p=<0.001); and lower pain severity at 1 to 1.5 follow up (-1.75 (95% CI: -2.98 to -0.51), p=0.006). Some of the results were characterized by a substantial, statistically significant heterogeneity. Nevertheless, a major part of the results pointed in the same direction, improving symptomatology with meditation-based therapy. The studies had a risk of bias mostly regarding the measurement of the outcome, randomization process and selection of the reported result. The current study discovered that the meditation group had significantly lower pain (at 1 to 1.5 months follow-up) anxiety, and depression scores and higher mindfulness scores at the end of the interventions.

BACKGROUND: In order to investigate microvascular complications in metabolic diseases, we aimed to investigate cerebral and peripheral microcirculation in relation to peripheral neuropathy and laboratory biomarkers in type 2 diabetes mellitus (T2DM) and obesity.
METHODS: Based on the degree of neuropathy (NP), study participants (40 T2DM and 30 obese individuals) were classified into no-NP, mild-NP and severe-NP subgroups. After the injection of Technetium-99 m hexamethylpropylene amine oxime, both T2DM and obese participants underwent single-photon emission computed tomography/computed tomography ([99mTc]Tc-HMPAO SPECT/CT) and SPECT-only examinations to assess lower limb and brain perfusion; respectively. Peripheral nerve function was evaluated with a neurometer and glycaemic markers were measured from plasma in both groups.
RESULTS: Compared to the obese individuals, lower extremity perfusion was significantly reduced in the diabetic subjects (p < 0.005), while it showed a positive correlation with C-peptide levels and negative association with HbA1c values. A U-shape pattern of peripheral microcirculation was observed between the NP groups, indicating a surprisingly better perfusion in the severe-NP group than in the mild one, with the highest levels in obese patients. Since changes in the C-peptide levels exhibited a similar U-shaped trend across the NP subgroups, we suggest a positive correlation between C-peptide levels and the extent of peripheral perfusion. Although, C-peptide values and cerebral microcirculation correlated positively (rho = 0.27), brain perfusion did not show any differences neither between the diabetic and the obese patients, nor between the NP subgroups (at p < 0.05).
CONCLUSIONS: Establishing the link between neuropathy and peripheral microcirculation, C-peptide seems to be a promising biomarker for the prediction of microvascular alterations in metabolic diseases. Of note, the dominance of metabolic factors over microvascular damage in the development of obesity-related neuropathy should be emphasized as well.

The development of combination antiretroviral therapy (cART) has transformed human immunodeficiency virus (HIV) infection from a lethal diagnosis into a chronic disease, and people living with HIV on cART can experience an almost normal life expectancy. However, these individuals often develop various complications that lead to a decreased quality of life, some of the most significant of which are neuropathic pain and the development of painful peripheral sensory neuropathy (PSN). Critically, although cART is thought to induce pain pathogenesis, the relative contribution of different classes of antiretrovirals has not been systematically investigated. In this study, we measured the development of pathological pain and peripheral neuropathy in mice orally treated with distinct antiretrovirals at their translational dosages. Our results show that only nucleoside reverse transcriptase inhibitors (NRTIs), not other types of antiretrovirals such as proteinase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase strand transfer inhibitors, and CCR5 antagonists, induce pathological pain and PSN. Thus, these findings suggest that NRTIs are the major class of antiretrovirals in cART that promote the development of neuropathic pain. As NRTIs form the essential backbone of multiple different current cART regimens, it is of paramount clinical importance to better understand the underlying mechanism to facilitate the design of less toxic forms of these drugs and/or potential mitigation strategies.

Chronic pain is a common consequence of breast cancer (BC) and its treatments. Pain neuroscience education (PNE) is a non-pharmacological intervention that adopts a biopsychosocial approach and has already been proven to be effective for different chronic pain syndromes. The present review aims to critically assess clinical trials comparing the efficacy of PNE to traditional biomedical education (BME) in reducing BC-related pain and improving quality of life. We conducted a literature search in scientific databases, including all studies regarding PNE use specifically for BC-related pain. Ongoing randomized controlled and observational studies were identified from ClinicalTrials.gov and congress proceedings. A total of eight clinical trials met the review criteria. The participants were all administered physical therapy and assigned to receive either BME or PNE interventions. Among the completed clinical studies, one reported no statistically relevant differences between the two groups, whereas the other showed lower levels of pain-related indexes in the PNE population compared to the BME one. While the current literature is inconclusive regarding the effectiveness of PNE for managing BC pain, we strongly support the need for further trials, as PNE could empower BC patients in both prevention of and coping with pain, offering the advantage of having no side effects.

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, even though treatable, remains a significant public health problem. It mainly impacts the skin, peripheral nerves, mucosa of the upper respiratory tract, and the eyes. In this case report, we present the case of a 64-year-old female with numerous hypopigmented patches with loss of sensations, madarosis, resorption of toes and digits, skin tightening, and diminution of vision. The skin over the hands exhibited thickening, leading to functional impairments that influenced both manual dexterity and mobility. The diagnosis of this unique case, showing a complex triad of lepromatous leprosy, scleroderma, and sclerotic cataract, was confirmed by clinical evaluation, skin biopsies, serological tests, and ophthalmic examination. Following this, the patient underwent dexamethasone-cyclophosphamide pulse therapy and multidrug treatment to halt the disease progression, prevent further disability, and reduce transmission. The case management addressed the issue of overlapping symptoms and conditions to provide appropriate care and cure to the patient. Public health initiatives under the National Leprosy Eradication Programme play an important role in promoting early diagnosis, effective treatment, and community empowerment, working toward a future where leprosy is no longer a threat to public health by preventing disability, reducing transmission, and combating the social stigma associated with it.