Diabetic neuropathy (DN) is one of the major microvascular complications of diabetes mellitus affecting 50% of the diabetic population marred by various unmet clinical needs. There is a need to explore newer pathological mechanisms for designing futuristic regimens for the management of DN. There is a need for post-transcriptional regulation of gene expression by non-coding RNAs (ncRNAs) to finetune different cellular mechanisms with significant biological relevance. MicroRNAs (miRNAs) are a class of small ncRNAs (~ 20 to 24 nucleotide length) that are known to regulate the activity of ~ 50% protein-coding genes through repression of their target mRNAs. Differential expression of these miRNAs is associated with the pathophysiology of diabetic neuropathy via regulating various pathways such as neuronal hyperexcitability, inflammation, axonal growth, regeneration, and oxidative stress. Of note, the circulating and extracellular vesicular miRNAs serve as potential biomarkers underscoring their diagnostic potential. Recent pieces of evidence highlight the potential of miRNAs in modulating the initiation and progression of DN and the possibility of developing miRNAs as treatment options for DN. In this review, we have elaborated on the role of different miRNAs as potential biomarkers and emphasized their druggable aspects for promising future therapies for the clinical management of DN.

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.

Peripheral neuropathies of the foot and ankle can be challenging to diagnose clinically due to concomitant traumatic and nontraumatic or degenerative orthopedic conditions. Although clinical history, physical examination, and electrodiagnostic testing comprised of nerve conduction velocities and electromyography are used primarily for the identification and classification of peripheral nerve disorders, MR neurography (MRN) can be used to visualize the peripheral nerves as well as the skeletal muscles of the foot and ankle for primary neurogenic pathology and skeletal muscle denervation effect. Proper knowledge of the anatomy and pathophysiology of peripheral nerves is important for an MRN interpretation.

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.

Catfish are a highly diverse group of fish comprising more than 3500 species found in both freshwater and marine ecosystems. Upon handling, they can inflict a sting, with certain species capable of inducing significant pain and injury to the affected extremity. The prevalence of aquatic activities, such as fishing by line or manual capture (\"noodling\"), increases the likelihood of catfish stings, making prompt identification and treatment an important aspect of managing such encounters. A case of a presumed catfish spine injury during noodling in Tallahassee, Florida, is presented. The pectoral fin penetrated the volar aspect of the patient\'s right hand resulting in immediate pain and numbness. Over the course of 2 weeks, the patient developed distal ulnar neuropathy with conduction block at the wrist level. Surgical exploration revealed the ulnar nerve to be grossly intact, but the area surrounding the terminal division point of the ulnar nerve in the hand displayed infiltration by fibrous tissue that entrapped the nerve and its branches. Following surgical release of the ulnar nerve and its terminal branches from the fibrous tissue, complete resolution of distal ulnar neuropathy was achieved. In this patient\'s case, the absence of foreign bodies and the lack of visible nerve damage suggest that the injury to the patient\'s hand was largely attributable to toxin-mediated proinflammatory response and fibrosis.

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.

Withania somnifera (W. somnifera) has a long history of safety in the amelioration of neuro-active ailments. The current study aims to explore Withania somnifera phyto-active principle anti-microbial, ant-neuropathic, and anti-inflammatory activities, and to modify these activities utilizing nano-cubosomes exploiting their mechanisms of action. Bio-guided fractionation technique was utilized, to identify the most phyto-active compound, using LC-MS-NMR online technique and biological models of diabetes, neuropathy, and inflammation. In-vitro antibacterial activity was also monitored. The HbA1c, in-vivo antioxidant (serum-catalase, TBARS, and GSH), serum insulin, and pro-inflammatory serum cytokines (TNF alpha, IL-six, and IL-ten) levels have been assessed to establish the anti-neuropathic and anti-inflammatory mechanisms. The nano-cubosomal formulations (CUB 1-3) were utilized to improve the W. somnifera most active compound efficacy. W. somnifera has shown ten major peaks; coagulin Q (10.2 %), dihydrowithanolide A (2.4 %), dihydrowithaferin D (1.8 %), physagulin D (7.6 %), withanoside V (2.3 %), withanolide A (WDA, 10.3 %), withafrin A (4.9 %), withaferin D (7.7 %), withanone 9 (9.9 %), withanolide D (4.8 %). The bio-guided fractionation technique utilizing LC-MS-NMR technique has proved that withanolide A (WDA) is the most phyto-active compound in W. somnifera. The latter has shown better results than WDA, which might be due to other effective compounds in Ws. However, CUB 3 (WDA nano-cubosomes dispersion) has shown more prominent anti-diabetic, anti-neuropathic, anti-inflammatory, and anti-bacterial potentials than Ws and WDA. Thus, CUB 3 modified WDA activity, and improved its efficacy. The normalization of HbA1c levels, increased insulin secretagogue potential, and the amelioration of the oxidative-stress may be the underlying Ws, WDA, and CUB 3 antidiabetic neuropathy mechanism. Moreover, the Ws, WDA, and CUB 1-3 anti-inflammatory mechanism might be due to the amelioration of the pro-inflammatory serum cytokines (decreasing TNF alpha and IL-six levels and increasing IL-ten). Thus, CUB 3 might be a powerful tool in augmenting Withania somnifera activity as an oral drug-delivery system and improving its efficacy against neuropathy and inflammation.