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Flaviviruses pose a major public health concern across the globe. Among them, Zika virus (ZIKV) is an emerging and reemerging arthropod-borne flavivirus that has become a major international public health problem following multiple large outbreaks over the past two decades. The majority of infections caused by ZIKV exhibit mild symptoms. However, the virus has been found to be associated with a variety of congenital neural abnormalities, including microcephaly in children and Guillain-Barre syndrome in adults. The exact prediction of the potential of ZIKV transmission is still enigmatic and underlines the significance of routine detection of the virus in suspected areas. ZIKV transmission from mother to fetus (including fetal abnormalities), viral presence in immune-privileged areas, and sexual transmission demonstrate the challenges in understanding the factors governing viral persistence and pathogenesis. This review illustrates the transmission patterns, epidemiology, control strategies (through vaccines, antivirals, and vectors), oncolytic aspects, molecular insights into neuro-immunopathogenesis, and other neuropathies caused by ZIKV. Additionally, we summarize in vivo and in vitro models that could provide an important platform to study ZIKV pathogenesis and the underlying governing cellular and molecular mechanisms., Competing Interests: The authors declare no conflicts of interest.

This systematic review explores the association between herpes zoster (HZ) infection and Ogilvie's syndrome (acute colonic pseudo-obstruction), evaluating how varicella-zoster virus (VZV) reactivation may contribute to autonomic dysfunction leading to intestinal obstruction. A comprehensive search was conducted in PubMed, Scopus, and Cochrane Library databases up to October 2024, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included case reports, clinical images, and letters reporting Ogilvie's syndrome secondary to HZ or VZV infection. After screening 219 publications and additional grey literature, 27 studies describing 28 cases met the inclusion criteria. Data were extracted on patient demographics, clinical manifestations, diagnostic methods, and outcomes. The quality of studies was assessed using the Joanna Briggs Institute critical appraisal checklist. The results from 27 studies encompassing 28 patients with intestinal pseudo-obstruction secondary to VZV or HZ infection indicated a mean age of 60 years, predominantly affecting males (71.5%). Notably, 47.6% had underlying immunosuppressive conditions. The primary clinical manifestations included abdominal distention and severe constipation. Most patients (93%) exhibited a herpetiform rash, primarily in thoracic dermatomes. Symptoms of pseudo-obstruction often preceded the rash (58%), and imaging in the vast majority revealed colonic distension with no intra-abdominal pathology. Treatment focused on conservative management of both pseudo-obstruction and HZ symptoms, with 93% of patients achieving full recovery, while the mortality rate was identified at 7%. The findings suggest that HZ-induced Ogilvie's syndrome may be an underdiagnosed condition, requiring a high index of suspicion, particularly in immunocompromised patients. Early recognition and conservative treatment can prevent unnecessary surgical interventions. Further studies are needed to clarify the pathophysiological mechanisms linking VZV reactivation to colonic pseudo-obstruction., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Loufopoulos et al.)

Nerve conduction studies are usually the first diagnostic step in peripheral nerve disorders and their results are the basis for planning further investigations. However, there are some commonplaces in the interpretation of electrodiagnostic findings in peripheral neuropathies that, although useful in the everyday practice, may be misleading: (1) conduction block and abnormal temporal dispersion are distinctive features of acquired demyelinating disorders; (2) hereditary neuropathies are characterized by uniform slowing of conduction velocity; (3) axonal neuropathies are simply diagnosed by reduced amplitude of motor and sensory nerve action potentials with normal or slightly slow conduction velocity. In this review, we reappraise the occurrence of uniform and non-uniform conduction velocity slowing, conduction block and temporal dispersion in demyelinating, dysmyelinating and axonal neuropathies attempting, with a translational approach, a correlation between electrophysiological and pathological features as derived from sensory nerve biopsy in patients and animal models. Additionally, we provide some hints to navigate in this complex field., (© 2024 Peripheral Nerve Society.)

The Golgi apparatus is an intracellular organelle that modifies cargo, which is transported extracellularly through the nucleus, endoplasmic reticulum, and plasma membrane in order. First, the general function of the Golgi is reviewed and, then, Golgi stress signaling is discussed. In addition to the six main Golgi signaling pathways, two pathways that have been increasingly reported in recent years are described in this review. The focus then shifts to neurological disorders, examining Golgi stress reported in major neurological disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The review also encompasses findings related to other diseases, including hypomyelinating leukodystrophy, frontotemporal spectrum disorder/amyotrophic lateral sclerosis, microcephaly, Wilson's disease, and prion disease. Most of these neurological disorders cause Golgi fragmentation and Golgi stress. As a result, strong signals may act to induce apoptosis.

Background: Disrupted protein homeostasis (proteostasis) has been demonstrated to facilitate the progression of various diseases. The cytosolic T-complex protein-1 ring complex (TRiC/CCT) was discovered to be a critical player in orchestrating proteostasis by folding eukaryotic proteins, guiding intracellular localisation and suppressing protein aggregation. Intensive investigations of TRiC/CCT in different fields have improved the understanding of its role and molecular mechanism in multiple physiological and pathological processes., Main Body: In this review, we embark on a journey through the dynamic protein folding cycle of TRiC/CCT, unraveling the intricate mechanisms of its substrate selection, recognition, and intriguing folding and assembly processes. In addition to discussing the critical role of TRiC/CCT in maintaining proteostasis, we detail its involvement in cell cycle regulation, apoptosis, autophagy, metabolic control, adaptive immunity and signal transduction processes. Furthermore, we meticulously catalogue a compendium of TRiC-associated diseases, such as neuropathies, cardiovascular diseases and various malignancies. Specifically, we report the roles and molecular mechanisms of TRiC/CCT in regulating cancer formation and progression. Finally, we discuss unresolved issues in TRiC/CCT research, highlighting the efforts required for translation to clinical applications, such as diagnosis and treatment., Conclusion: This review aims to provide a comprehensive view of TRiC/CCT for researchers to inspire further investigations and explorations of potential translational possibilities., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The authors aimed to explore carpal tunnel syndrome (CTS) among electronic sports (esports) athletes, to compare hand symptoms and their severity between esports athletes and the control group and within the esports athletes, and to study the relationship between esports athletes' variables., Material and Methods: A cross-sectional survey study via telephone with systematic randomized approach was used for esport athletes sampling. Control group were non-esports athletes who do not use computer for prolonged duration. The survey consisted of sports athletes' characteristics, hand symptoms and functions, and the Boston Carpal Tunnel Questionnaire (BCTQ). The unpaired student's t-test, Mann-Whitney U test, and χ 2 test were utilised for statistical comparison, with p < 0.05. Pearson's and Spearman's correlation coefficient tests were used for relationship analyses., Results: Eligible participants were 198 out of 229. Compared to control group, esport athletes reported more CTS (p = 0.01), and radiated pain and numbness in their hands (p = 0.05). Males complained of hand symptoms (p < 0.01) and its radiation (p < 0.01) more than females among esports athletes. Higher BCTQ Symptom Severity Scale (BCTQ-SSS) scores were reported for esports athletes who had been playing esports for prolonged periods compared to those who had playing recently (p = 0.003), with a moderate positive correlation (+0.59, p = 0.004). A significant moderate positive correlation was reported for BCTQ Functional Severity Symptoms (BCTQ-FSS) scores in terms of hours of playing (+0.44, p = 0.04). Esports athletes who used armrests and a PC with a controller for gaming reported less hand symptoms and had milder BCTQ scores than those who used a PC with a keyboard/mouse. Generally, esports athletes spend 5-10 h/day on gaming., Conclusions: Esports athletes might be at risk of developing upper-extremity nerve compression and CTS. Prolonged playing, hours of playing, type of esports device, and using armrests are possible risk factors. Med Pr Work Health Saf. 2023;74(4):279-87., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Connective tissue disorders (CTD) are a group of disorders affecting the connective tissues. Usually the musculoskeletal and the vascular system is impacted. Along with these systems, the nervous system is also involved in CTD, which leads to various neurological manifestations. The pathophysiology of neurological complications of CTD is caused by various factors and is complicated. Disturbed immune complexes, chronic inflammation, and autoimmunity in which the body attacks its cells are considered to be responsible for the neurological complications of CTD. Additionally, the vascular symptoms that lead to decreased blood flow to the brain are also responsible for the neurological manifestations of CTD in diseases like systemic lupus erythematosus (SLE). In SLE, vessel wall integrity is compromised, which may lead to decreased blood flow leading to neurological complications. CTD can manifest a variety of neurological complications. These neurological complications can be classified into symptoms affecting the peripheral nervous system, central nervous system, and the autonomic nervous system. Some of the common neurological complications of CTD are headaches, seizures, ataxia, neuropathies leading to cranial nerve palsies, myelopathies, tremors, encephalitis, and cerebral infarction. Cranial nerve palsies can disturb sensations, vision, hearing, and mastication. Neuropsychiatric symptoms are also commonly observed in CTD. Cognitive dysfunction can be caused due to neuropsychiatric problems. Some of the cognitive dysfunctions are lack of concentration, memory loss, confusion, and coma. In this review, we will address various neurological manifestations of CTD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Poshattiwar et al.)

Peripheral nervous system diseases are a complex and heterogenous group of diseases affecting the different nerves with various severity and impact on quality of life. The current literature does not provide a structured guide for the rehabilitation of these conditions. We performed a lexical literature evaluation based on graph theory to clarify this topic. We performed a search on PubMed and calculated the frequencies of the words indicating rehabilitation approaches, nerves, and diseases. We found the usefulness of exercises and different physical agents, like laser and ultrasound therapy and neuromuscular stimulation vibration therapy. Orthoses are useful for entrapment, trauma, and hereditary diseases. Correct knowledge and assessment of the neuropathies are fundamental for the therapeutic decision and to guide rehabilitation. Despite the usefulness shown by the different approaches to modulating pain, improving muscle strength and endurance, and ameliorating balance and the sensory system, further studies are needed to define the best-personalized protocols.

Introduction: Bruton's tyrosine kinase (BTK) is a multifaceted player of the immune system which has been involved in the survival of hematological malignancies but also in the pathogenesis of immune-mediated diseases. Oral BTK inhibitors (BTKi) have become a cornerstone for the treatment of patients with B-cell malignancies, and are under investigation for several immune-mediated diseases., Areas Covered: We reviewed the biology of BTK and emerging data on BTKi in patients with neuroinflammatory disorders of both the peripheral and central nervous system., Expert Opinion: We support the use of BTKi in relapsed/refractory patients with multiple sclerosis and anti-MAG antibody neuropathies. However, other immune-mediated neuroinflammatory disorders are likely to benefit from BTKi. Whether BTKi will improve the response rates than conventional therapies in previously untreated patients is unknown and will be assessed within future clinical trials. Furthermore, the availability of more selective BTKi, with less adverse events, will improve patients' tolerability and expand our treatment landscape.

Long COVID is an emerging problem in the current health care scenario. It is a syndrome with common symptoms of shortness of breath, fatigue, cognitive dysfunction, and other conditions that have a high impact on daily life. They are fluctuating or relapsing states that occur in patients with a history of SARS-CoV-2 infection for at least 2 months. They are usually conditions that at 3 months after onset cannot be explained by an alternative diagnosis. Currently very little is known about this syndrome. A thorough review of the literature highlights that the cause is attributable to deposits of tau protein. Massive phosphorylation of tau protein in response to SARS-CoV-2 infection occurred in brain samples from autopsies of people previously affected with COVID-19. The neurological disorders resulting from this clinical condition are termed tauopathies and can give different pathological symptoms depending on the involved anatomical region of the brain. Peripheral small-fiber neuropathies are also evident among patients with Long COVID leading to fatigue, which is the main symptom of this syndrome. Certainly more research studies could confirm the association between tau protein and Long COVID by defining the main role of tau protein as a biomarker for the diagnosis of this syndrome that is widespread in the post-pandemic period., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The indications for nerve biopsy have diminished in recent years. This examination nevertheless remains essential in certain cases of peripheral neuropathies, making it possible to specify the diagnosis or the mechanism of injury for a therapeutic purpose. It is a simple but "invasive" procedure, which can only be performed once on the same nerve. The indications are thus discussed on a case-by-case basis and based on a range of clinical, electrophysiological, biological or even genetic arguments. This involves close collaboration between clinical physicians and pathologists. The main difficulty of this biopsy concerns the fragility of the sample and the techniques necessary for its interpretation, requiring it to be carried out in expert centers. Nerve biopsy is closely related to skin biopsy in the search for small fiber neuropathy. It is a particular technique, but very well codified. The purpose of this review is to recall the indications and contraindications of nerve biopsy, and to explain what the contributions are but also the limits of this examination as well as of skin biopsy., (Copyright © 2022. Published by Elsevier Masson SAS.)

Repair of genomic DNA is a fundamental housekeeping process that quietly maintains the health of our genomes. The consequences of a genetic defect affecting a component of this delicate mechanism are quite harmful, characterized by a cascade of premature aging that injures a variety of organs, including the nervous system. One part of the nervous system that is impaired in certain DNA repair disorders is the peripheral nerve. Chronic motor, sensory, and sensorimotor polyneuropathies have all been observed in affected individuals, with specific physiologies associated with different categories of DNA repair disorders. Cockayne syndrome has classically been linked to demyelinating polyneuropathies, whereas xeroderma pigmentosum has long been associated with axonal polyneuropathies. Three additional recessive DNA repair disorders are associated with neuropathies, including trichothiodystrophy, Werner syndrome, and ataxia-telangiectasia. Although plausible biological explanations exist for why the peripheral nerves are specifically vulnerable to impairments of DNA repair, specific mechanisms such as oxidative stress remain largely unexplored in this context, and bear further study. It is also unclear why different DNA repair disorders manifest with different types of neuropathy, and why neuropathy is not universally present in those diseases. Longitudinal physiological monitoring of these neuropathies with serial electrodiagnostic studies may provide valuable noninvasive outcome data in the context of future natural history studies, and thus the responses of these neuropathies may become sentinel outcome measures for future clinical trials of treatments currently in development such as adeno-associated virus gene replacement therapies., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

The plastic potential of Schwann cells (SCs) is increasingly recognized to play a role after nerve injury and in diseases of the peripheral nervous system. Reports on the interaction between immune cells and SCs indicate their involvement in inflammatory processes. However, the immunocompetence of human SCs has been primarily deduced from neuropathies, but whether after nerve injury SCs directly regulate an adaptive immune response is unknown. Here, we performed comprehensive analysis of immunomodulatory capacities of human repair-related SCs (hrSCs), which recapitulate SC response to nerve injury in vitro. We used our well-established culture model of primary hrSCs from human peripheral nerves and analyzed the transcriptome, secretome, and cell surface proteins for pathways and markers relevant in innate and adaptive immunity, performed phagocytosis assays, and monitored T-cell subset activation in allogeneic co-cultures. Our findings show that hrSCs are phagocytic, which is in line with high MHCII expression. Furthermore, hrSCs express co-regulatory proteins, such as CD40, CD80, B7H3, CD58, CD86, and HVEM, release a plethora of chemoattractants, matrix remodeling proteins and pro- as well as anti-inflammatory cytokines, and upregulate the T-cell inhibiting PD-L1 molecule upon pro-inflammatory stimulation with IFNγ. In contrast to monocytes, hrSC alone are not sufficient to trigger allogenic CD4 + and CD8 + T-cells, but limit number and activation status of exogenously activated T-cells. This study demonstrates that hrSCs possess features and functions typical for professional antigen-presenting cells in vitro, and suggest a new role of these cells as negative regulators of T-cell immunity during nerve regeneration., (© 2022 The Authors. GLIA published by Wiley Periodicals LLC.)

Chronic immune-mediated neuropathies, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), neuropathies associated with monoclonal gammopathy, and multifocal motor neuropathy (MMN), are a group of disorders deemed to be caused by an immune response against peripheral nerve antigens. Several immune therapies have been reported to be variably effective in these neuropathies including steroids, plasma exchange, and high-dose intravenous (IVIg) or subcutaneous (SCIg) immunoglobulins. These therapies are however far from being invariably effective and may be associated with a number of side effects leading to the use of immunosuppressive agents whose efficacy has not been so far confirmed in randomized trials. More recently, new biological agents, such as rituximab, have proved to be effective in patients with neuropathy associated with IgM monoclonal gammopathy and are currently tested in CIDP., (© 2021. Fondazione Società Italiana di Neurologia.)

Mycobacterium leprae infection of peripheral nerves and the subsequent nerve function impairment (NFI), especially in response to reactional episodes, are hallmarks of leprosy. Improved treatments for M. leprae -induced nerve injury are needed, as most if not all of the disability and stigma associated with leprosy arises from the direct or indirect effects of NFI. Nine-banded armadillos ( Dasypus novemcinctus ), like humans, exhibit the full clinical spectrum of leprosy and extensive involvement of the peripheral nerves. In this study, state-of-the-art technology was used to compare nerve function between uninfected and M. leprae -infected armadillos. Motor nerve conduction velocity (MNCV) and compound muscle action potential (cMAP), which measure changes in the rate of impulse conduction velocity and amplitude, revealed a progression of impairment that was directly correlated with the duration of M. leprae infection and enabled development of an objective nerve impairment scoring system. Ultrasonography accompanied by color Doppler imaging detected enlargement of the M. leprae -infected nerves and increased vascularity, possibly due to inflammation. Assessment of epidermal nerve fiber density (ENFD), which shows a length-dependent innervation in armadillos that is similar to humans, identified small fiber degeneration early after M. leprae infection. Staining for neuromuscular junction (NMJ) integrity, which is an indicator of signal transduction efficiency into skeletal muscle, discerned a markedly lower number and structural integrity of NMJ in M. leprae -infected armadillo footpads. These tools for assessing nerve injury were used to monitor the effects of intervention therapy. Two potential neuro-protective drugs, ethoxyquin (EQ) and 4-aminopyridine (4-AP), were tested for their ability to ameliorate peripheral nerve injury in M. leprae -infected armadillos. 4-AP treatment improved MNCV, cMAP, and EFND compared to untreated animals, while EQ had less effect. These results support the armadillo as a model for M. leprae -induced peripheral nerve injury that can provide insights toward the understanding of NFI progression and contribute to the preclinical investigation of the safety and efficacy of neuro-preventive and neuro-therapeutic interventions for leprosy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pena, Lahiri, Ebenezer, Wheat, Figarola, Truman and Adams.)

Recognition of diseases associated with mutations of the chaperone system genes, e.g., chaperonopathies, is on the rise. Hereditary and clinical aspects are established, but the impact of the mutation on the chaperone molecule and the mechanisms underpinning the tissue abnormalities are not. Here, histological features of skeletal muscle from a patient with a severe, early onset, distal motor neuropathy, carrying a mutation on the CCT5 subunit (MUT) were examined in comparison with normal muscle (CTR). The MUT muscle was considerably modified; atrophy of fibers and disruption of the tissue architecture were prominent, with many fibers in apoptosis. CCT5 was diversely present in the sarcolemma, cytoplasm, and nuclei in MUT and in CTR and was also in the extracellular space; it colocalized with CCT1. In MUT, the signal of myosin appeared slightly increased, and actin slightly decreased as compared with CTR. Desmin was considerably delocalized in MUT, appearing with abnormal patterns and in precipitates. Alpha-B-crystallin and Hsp90 occurred at lower signals in MUT than in CTR muscle, appearing also in precipitates with desmin. The abnormal features in MUT may be the consequence of inactivity, malnutrition, denervation, and failure of protein homeostasis. The latter could be at least in part caused by malfunction of the CCT complex with the mutant CCT5 subunit. This is suggested by the results of the in silico analyses of the mutant CCT5 molecule, which revealed various abnormalities when compared with the wild-type counterpart, mostly affecting the apical domain and potentially impairing chaperoning functions. Thus, analysis of mutated CCT5 in vitro and in vivo is anticipated to provide additional insights on subunit involvement in neuromuscular disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Scalia, Barone, Rappa, Marino Gammazza, Lo Celso, Lo Bosco, Barone, Antona, Vadalà, Vitale, Donato Mangano, Amato, Sentiero, Macaluso, Myburgh, Conway de Macario, Macario, Giuffrè and Cappello.)

Introduction: The aim of this study is to investigate a possible association between vitamin D deficiency and diabetic peripheral neuropathy in pediatric patients with type 1 diabetes mellitus., Materials-Methods: Twenty-nine patients with type 1 diabetes mellitus and 19 healthy controls were included to the study. All individuals were evaluated for diabetic peripheral neuropathy with nerve conduction studies. Complete blood cell count, biochemical investigations, serum vitamin D levels, hemoglobin A1c levels were recorded., Results: No statistically significant differences between the diabetes and control groups in terms of gender, age, body weight, height, body mass index, systolic and diastolic blood pressures, laboratory investigations, serum vitamin D levels and nerve conduction studies was found. Patients with diabetes were grouped as patients with normal serum vitamin D levels and patients with vitamin D deficiency. Sensory nerve action potential of sural nerve and motor peroneal nerve velocity were statistically significantly lower in diabetic patients with vitamin D deficiency compared to diabetic patients with normal vitamin D levels (p 0.009 and 0.005 respectively)., Conclusion: Our results suggested that hypovitaminosis D might lead to development of neuropathic changes particularly on the lower limb nerves even in the early stages of the disease. It should be kept in mind that patients with hypovitaminosis D should be elaborately examined and closely followed up for the development of diabetic neuropathic changes, even if glucose control is achieved., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Inflammatory neuropathies are a group of acquired neuropathies which could be due to autoimmune, infectious, paraneoplastic, or paraproteinemic etiology. The etiological diagnosis of inflammatory neuropathy is not simple, and often requires combination of clinical, electrophysiological, and histopathological findings to arrive at a precise diagnosis which is important for management of the disorder. Whereas there are comprehensive and sensitive panel of serological tests available for diagnosis of the infectious, paraneoplastic, paraproteinemic neuropathies, the diagnosis of immune-mediated demyelinating neuropathies remain a considerable challenge as there is both clinical and pathological overlap. Newer non-invasive methodologies such as high-resolution ultrasound, magnetic resonance imaging (MRI), and importantly, serological testing for antibodies are emerging, and it is essential for the practicing pathologist to be up-to-date with emerging modalities. In this review, we focus on the approach to diagnosis of immune-mediated demyelinating neuropathies., Competing Interests: None

Sensory and autonomic neuropathy was diagnosed in a five-month-old Border Collie puppy, who presented with progressive self-mutilation, proprioceptive ataxia and urinary incontinence. In the Border Collie, sensory neuropathy is different from what is observed in acral mutilation syndrome, as the genetic mutation is linked to an inversion disrupting the FAM134B gene. Diagnosis was based on history, clinical signs and genetic testing. The prognosis of sensory neuropathies is poor and no curative treatment is available. In the present case, oclacitinib was started for symptomatic treatment of the self-mutilation. A good control of the self-mutilation was quickly observed with an improvement in quality of life for five months. Unfortunately, progression of neurological signs with severe proprioceptive deficits, ataxia, muscular atrophy and urinary/fecal incontinence was observed. Five months after diagnosis, the owner elected for euthanasia.

Immune checkpoint inhibitors have entailed a change of paradigm in the management of multiple malignant diseases and are acquiring a key role in an increasing number of clinical sceneries. However, since their mechanism of action is not limited to the tumor microenvironment, their systemic activity may lead to a wide spectrum of immune-related side effects. Although neurological adverse events are much less frequent than gastrointestinal, hepatic, or lung toxicity, with an incidence of <5%, their potential severity and consequent interruptions to cancer treatment make them of particular importance. Despite them mainly implying peripheral neuropathies, immunotherapy has also been associated with an increased risk of encephalitis and paraneoplastic disorders affecting the central nervous system, often appearing in a clinical context where the appropriate diagnosis and early management of neuropsychiatric symptoms can be challenging. Although the pathogenesis of these complications is not fully understood yet, the blockade of tumoral inhibitory signals, and therefore the elicitation of cytotoxic T-cell-mediated response, seems to play a decisive role. The aim of this review was to summarize the current knowledge about the pathogenic mechanisms, clinical manifestations, and therapeutic recommendations regarding the main forms of neurotoxicity related to checkpoint inhibitors., Competing Interests: CS travel and educational support: Novartis, Lilly, Pfizer, MSD, BMS. AS travel and educational support: MSD, BMS, and Pierre Fabre and has served as advisor and delivered lectures for Novartis, MSD, BMS, Sanofi Aventis, Pierre Fabre, and Merck Serono. PG travel and educational support: Pfizer, Ipsen, Sanofi-Genzyne, Roche, and Jansen and has served as advisor and delivered lectures for BMS, MSD, Merck Serono, Pfizer, Ipsen, Roche, Adacap, Eisai, Sanofi-Genzyme, Novartis, and Jansen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Albarrán, Chamorro, Rosero, Saavedra, Soria, Carrato and Gajate.)

Aim of the Study: Systematic review and meta-analysis to assess the effectiveness of manual therapy in improving carpal tunnel syndrome (CTS) symptoms, physical function, and nerve conduction studies., Method: MEDLINE, Web of Science, SCOPUS, Cochrane Library, TRIP database, and PEDro databases were searched from the inception to September 2021. PICO search strategy was used to identify randomized controlled trials applying manual therapy on patients with CTS. Eligible studies and data extraction were conducted independently by two reviewers. Methodology quality and risk of bias were assessed by PEDro scale. Outcomes assessed were pain intensity, physical function, and nerve conduction studies., Results: Eighty-one potential studies were identified and six studies involving 401 patients were finally included. Pain intensity immediately after treatment showed a pooled standard mean difference (SMD) of - 2.13 with 95% confidence interval (CI) (- 2.39, - 1.86). Physical function with Boston Carpal Tunnel Syndrome Questionnaire (BCTS-Q) showed a pooled SMD of - 1.67 with 95% CI (- 1.92, - 1.43) on symptoms severity, and a SMD of - 0.89 with 95% CI (- 1.08, - 0.70) on functional status. Nerve conduction studies showed a SMD of - 0.19 with 95% CI (- 0.40, - 0.02) on motor conduction and a SMD of - 1.15 with 95% CI (- 1.36, - 0.93) on sensory conduction., Conclusions: This study highlights the effectiveness of manual therapy techniques based on soft tissue and neurodynamic mobilizations, in isolation, on pain, physical function, and nerve conduction studies in patients with CTS., (© 2021. The Author(s).)

Toxoplasmosis is a prevalent disease affecting a wide range of hosts including approximately one-third of the human population. It is caused by the sporozoan parasite Toxoplasma gondii ( T. gondii ), which instigates a range of symptoms, manifesting as acute and chronic forms and varying from ocular to deleterious congenital or neuro-toxoplasmosis. Toxoplasmosis may cause serious health problems in fetuses, newborns, and immunocompromised patients. Recently, associations between toxoplasmosis and various neuropathies and different types of cancer were documented. In the veterinary sector, toxoplasmosis results in recurring abortions, leading to significant economic losses. Treatment of toxoplasmosis remains intricate and encompasses general antiparasitic and antibacterial drugs. The efficacy of these drugs is hindered by intolerance, side effects, and emergence of parasite resistance. Furthermore, all currently used drugs in the clinic target acute toxoplasmosis, with no or little effect on the chronic form. In this review, we will provide a comprehensive overview on the currently used and emergent drugs and their respective parasitic targets to combat toxoplasmosis. We will also abridge the repurposing of certain drugs, their targets, and highlight future druggable targets to enhance the therapeutic efficacy against toxoplasmosis, hence lessening its burden and potentially alleviating the complications of its associated diseases.

Age-related muscle loss is a phenomenon that has been extensively studied in recent decades. Sarcopenia is a multisystem disease, which predisposes to muscle weakness and frailty. At around 50 years of age, an individual begins to lose muscle strength, although this becomes more evident after 70. Sarcopenia is a condition typically found in older adults but can also affect younger people. Sarcopenia is a preventable and treatable condition. In past years, methods and tools to recognize the condition early have been researched. For the development of therapeutic interventions, agreement on diagnosis is fundamental. In recent years, a possible role of ultrasonography in the diagnosis of sarcopenia has been evaluated, compared with the best-known techniques.

Background: Neuropathy is a common chronic complication in type 2 diabetes mellitus (T2DM). Statin and metformin are commonly used medications in T2DM patients, and some studies showed statin- or metformin-induced neuropathy., Aim: To evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies., Methods: Korean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used. Patients with T2DM and no complications were divided into statin/metformin/statin + metformin users and non-users. Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems, 10 th revision codes and concomitant prescriptions for anticonvulsants or antidepressants. Logistic regression analyses were conducted to examine the associations between statin/metformin/statin + metformin therapies and the incidence of neuropathy. Propensity score (PS) matching was performed on the basis of age, sex and comorbidities., Results: Overall, 34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017, respectively. Statin therapy was associated with increased risks of neuropathy in 2016 and 2017 [PS-matched odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.08-1.38; PS-matched OR = 1.17, 95%CI: 1.03-1.33, respectively]. Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017 (PS-matched OR = 0.30, 95%CI: 0.21-0.42; PS-matched OR = 0.44, 95%CI: 0.32-0.60, respectively). Combined statin + metformin therapy was not significantly associated with neuropathy in 2016 or 2017 (PS-matched OR = 0.85, 95%CI: 0.61-1.19; PS-matched OR = 0.95, 95%CI: 0.66-1.38, respectively)., Conclusion: Statin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM, but metformin therapy showed the opposite association., Competing Interests: Conflict-of-interest statement: The authors have no potential conflicts of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Toxoplasma gondii ( T. gondii ) is a prevalent protozoan parasite of medical and veterinary significance. It is the etiologic agent of toxoplasmosis, a neglected disease in which incidence and symptoms differ between patients and regions. In immunocompetent patients, toxoplasmosis manifests as acute and chronic forms. Acute toxoplasmosis presents as mild or asymptomatic disease that evolves, under the host immune response, into a persistent chronic disease in healthy individuals. Chronic toxoplasmosis establishes as latent tissue cysts in the brain and skeletal muscles. In immunocompromised patients, chronic toxoplasmosis may reactivate, leading to a potentially life-threatening condition. Recently, the association between toxoplasmosis and various diseases has been shown. These span primary neuropathies, behavioral and psychiatric disorders, and different types of cancer. Currently, a direct pre-clinical or clinical molecular connotation between toxoplasmosis and most of its associated diseases remains poorly understood. In this review, we provide a comprehensive overview on Toxoplasma -induced and associated diseases with a focus on available knowledge of the molecular players dictating these associations. We will also abridge the existing therapeutic options of toxoplasmosis and highlight the current gaps to explore the implications of toxoplasmosis on its associated diseases to advance treatment modalities.

Proteasome inhibition with bortezomib has been reported to exert an immunomodulatory action in chronic autoimmune neuropathies. However, bortezomib used for the treatment of multiple myeloma induces a painful toxic polyneuropathy at a higher concentration. Therefore, we addressed this controversial effect and evaluated the neurotoxic and immunomodulatory mode of action of bortezomib in experimental autoimmune neuritis. Bortezomib-induced neuropathy was investigated in Lewis rats using the von Frey hair test, electrophysiological, qPCR and histological analyses of the sciatic nerve as well as dorsal root ganglia outgrowth studies. The immunomodulatory potential of bortezomib was characterized in Lewis rats after experimental autoimmune neuritis induction with P2 53-78 peptide. Clinical, electrophysiological, histological evaluation, von Frey hair test, flow cytometric and mRNA analyses were used to unravel the underlying mechanisms. We defined the toxic concentration of 0.2 mg/kg bortezomib applied intraperitoneally at Days 0, 4, 8 and 12. This dosage induces a painful toxic neuropathy but preserves axonal regeneration in vitro . Bortezomib at a concentration of 0.05 mg/kg significantly ameliorated experimental autoimmune neuritis symptoms, improved experimental autoimmune neuritis-induced hyperalgesia and nerve conduction studies, and reduced immune cell infiltration. Furthermore, proteasome inhibition induced a transcriptional downregulation of Nfkb in the sciatic nerve, while its inhibitor Ikba (also known as Nfkbia ) was upregulated. Histological analyses of bone marrow tissue revealed a compensatory increase of CD138 + plasma cells. Our data suggest that low dose bortezomib (0.05 mg/kg intraperitoneally) has an immunomodulatory effect in the context of experimental autoimmune neuritis through proteasome inhibition and downregulation of nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFKB). Higher bortezomib concentrations (0.2 mg/kg intraperitoneally) induce sensory neuropathy; however, the regeneration potential remains unaffected. Our data empathizes that bortezomib may serve as an attractive treatment option for inflammatory neuropathies in lower concentrations., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The quality of healing of peripheral nerve injuries remains a common challenge causing pain and poor quality of life for millions of people and animals annually., Aims: The objectives of this study were to evaluate the healing quality of facial nerve injury in a dog model following local treatment using an autologous injection of platelet-rich plasma (PRP) or bone marrow-derived mesenchymal stem cells (BM-MSCs) at the injury site in combination with the application of an autologous saphenous vein graft as a conduit., Methods: 20 apparently healthy adult Mongrel dogs were randomly divided into 4 equal groups. Dogs in groups 1, 2, and 3 were subjected to facial nerve neurectomy and saphenous vein conduit graft implantation at the site of facial nerve injury. Dogs in groups 2 and 3 received 1 ml of autologous PRP and BM-MSCs, respectively. Injections were administered directly in the vein conduit immediately after nerve injury. Dogs in group 1 (grafted but not treated; control) received only an autologous vein graft, and those in group 4 (normal control) received no graft and no PRP or BM-MSCs treatment. The dogs were monitored daily for 8 weeks after surgery. Clinical evaluation of the facial nerve, including lower eyelid, ear drooping, upper lip, and tongue functions, was carried out once per week using a numerical scoring system of 0-3. At the end of the study period (week 8), the facial nerve injury site was evaluated grossly for the presence of adhesions using a numerical scoring system of 0-3. The facial nerve injury site was histopathologically assessed for the existence of perivascular mononuclear cell infiltration, fibrous tissue deposition, and axonal injury using H&E-stained tissue sections., Results: Clinically, BM-MSCs treated dogs experienced significant ( p < 0.05) improvement in the lower eyelid, ear, lip, and tongue functions 4 weeks postoperatively compared to other groups. Grossly, the facial nerve graft site in the BM-MSCs treated group showed significantly ( p < 0.05) lesser adhesion scores than the other groups. Histopathologically, there was significantly ( p < 0.05) less perivascular mononuclear cell infiltration, less collagen deposition, and more normal axons at the facial nerve injury site in the BM-MSCs treated group compared to the other groups., Conclusion: This study showed clinically significant enhancement of nerve regeneration by applying autologous BM-MSCs and autologous vein grafting at the site of facial nerve injury. However, further clinical trials are warranted before this application can be recommended to treat traumatic nerve injuries in the field., Competing Interests: The authors declare that they have no competing interests.

Running is an athletic activity that is increasingly gaining popularity. Despite its benefits, there are many suspected risk factors for running-related overuse injuries. The objective of this study is to describe injuries and clinical symptoms observed on the sole of the foot in runners, giving special attention to the weekly running volume. The literature presented in this narrative review is based on a non-systematic search of the Medline, Google Scholar, and ResearchGate databases and focuses on foot injuries (the full spectrum of the foot pathology from bones to tendons and plantar fascia, nerve, and joint disorders) in runners, which represents an important topic for both professional and recreational runners. The weekly running distance appeared to be one of the strongest predictors for future overuse injuries. Marathon training and average weekly running of over 20 km are possible predictive factors in the development of plantar foot injuries. The plantar medial aspect of the foot is the anatomic area of the foot that most frequently experiences pain, with numerous pathologic conditions. As a result, diagnosis is always a challenging task. The ability to obtain an accurate medical history and carefully perform a physical examination, together with good knowledge of the foot anatomy and kinesiology, are also proven to be key players in ensuring proper diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Vasiliadis et al.)

This review describes the roles of the low-density lipoprotein receptor-related protein 1 (LRP-1) in inflammatory pathways, nerve nerve degeneration and -regeneration and in neuropathic pain. Induction of LRP-1 is able to reduce the activation of the proinflammatory NFκB-mediated pathway and the mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase and p38 signaling pathways, in turn decreasing the production of inflammatory mediators. Low-density lipoprotein receptor-related protein 1 activation also decreases reactive astrogliosis and polarizes microglial cells and macrophages from a proinflammatory phenotype (M1) to an anti-inflammatory phenotype (M2), attenuating the neuroinflammatory environment. Low-density lipoprotein receptor-related protein 1 can also modulate the permeability of the blood-brain barrier and the blood-nerve barrier, thus regulating the infiltration of systemic insults and cells into the central and the peripheral nervous system, respectively. Furthermore, LRP-1 is involved in the maturation of oligodendrocytes and in the activation, migration, and repair phenotype of Schwann cells, therefore suggesting a major role in restoring the myelin sheaths upon injury. Low-density lipoprotein receptor-related protein 1 activation can indirectly decrease neurodegeneration and neuropathic pain by attenuation of the inflammatory environment. Moreover, LRP-1 agonists can directly promote neural cell survival and neurite sprouting, decrease cell death, and attenuate pain and neurological disorders by the inhibition of MAPK c-Jun N-terminal kinase and p38-pathway and activation of MAPK extracellular signal-regulated kinase pathway. In addition, activation of LRP-1 resulted in better outcomes for neuropathies such as Alzheimer disease, nerve injury, or diabetic peripheral neuropathy, attenuating neuropathic pain and improving cognitive functions. To summarize, LRP-1 plays an important role in the development of different experimental diseases of the nervous system, and it is emerging as a very interesting therapeutic target., Competing Interests: The authors have no conflicts of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Peripheral neuropathy in patients with rheumatoid arthritis is associated with a maladaptive autoimmune response that may cause chronic pain and disability. Nerve conduction studies are the routine method performed when rheumatologists presume its presence. However, this approach is invasive, may not reveal subtle malfunctions in the early stages of the disease, and does not expose abnormalities in structures surrounding the nerves and muscles, limiting the possibility of a timely diagnosis. This work aims to present a narrative review of new technologies for the clinical assessment of peripheral neuropathy in Rheumatoid Arthritis. Through a bibliographic search carried out in five repositories, from 1990 to 2020, we identified three technologies that could detect peripheral nerve lesions and perform quantitative evaluations: (1) magnetic resonance neurography, (2) functional magnetic resonance imaging, and (3) high-resolution ultrasonography of peripheral nerves. We found these tools can overcome the main constraints imposed by the previous electrophysiologic methods, enabling early diagnosis.

COVID-19 can affect the central nervous system (CNS) indirectly by inflammatory mechanisms and even directly enter the CNS. Thereby, COVID-19 can evoke a range of neurosensory conditions belonging to infectious, inflammatory, demyelinating, and degenerative classes. A broad range of non-specific options, including anti-viral agents and anti-inflammatory protocols, is available with varying therapeutic. Due to the high mortality and morbidity in COVID-19-related brain damage, some changes to these general protocols, however, are necessary for ensuring the delivery of therapeutic(s) to the specific components of the CNS to meet their specific requirements. The biomaterials approach permits crossing the blood-brain barrier (BBB) and drug delivery in a more accurate and sustained manner. Beyond the BBB, drugs can protect neural cells, stimulate endogenous stem cells, and induce plasticity more effectively. Biomaterials for cell delivery exist, providing an efficient tool to improve cell retention, survival, differentiation, and integration. This paper will review the potentials of the biomaterials approach for the damaged CNS in COVID-19. It mainly includes biomaterials for promoting synaptic plasticity and modulation of inflammation in the post-stroke brain, extracellular vesicles, exosomes, and conductive biomaterials to facilitate neural regeneration, and artificial nerve conduits for treatment of neuropathies. Also, biosensing surfaces applicable to the first sensory interface between the host and the virus that encourage the generation of accelerated anti-viral immunity theoretically offer hope in solving COVID-19., (© Qatar University and Springer Nature Switzerland AG 2021.)

The symptomatology of Charcot-Marie-Tooth (CMT) disease mainly involves the feet and the hands. To date, there is no consensus on how to evaluate hand function in CMT. The aim of this study is to correlate the data of the engineered glove Hand Test System (HTS) with specific tests and the CMT examination score (CMTES). We analyzed 45 patients with the diagnosis of CMT using HTS, which measures the hand dexterity by specific sequences performed at maximum velocity. We completed the evaluation with the CMTES, tripod pinch and hand grip strength tested by a dynamometer, thumb opposition test (TOT), and Sollerman Hand function test (SHFT), and we conducted a test-retest with 20 normal subjects. Finger tapping (FT) and index-medium-ring-little (IMRL) sequence showed a significant correlation with CMTES (FT: dominant hand (DH): P = .036; non-dominant hand (NDH): P = .033; IMRL: DH: P = .009; NDH: P = .046). TOT correlated with CMTES significantly in both hands (P < .0001). tripod pinch showed a statistically significant correlation with CMTES (DH: P = .002; NDH: P = .005). Correlation between the hand grip and CMTES was significant only in DH (DH: P = .002). SHFT had a significant correlation with the CMTES (DH: P = .002). Test-retest showed a good reliability. HTS parameters correlate with CMTES confirming that this tool is sensitive to the hand deficits. In conclusion, we can state that HTS is a good, simple to use, and objective instrument to evaluate the hand function of CMT patients, but more studies on responsiveness and sensitivity are needed., (© 2020 Peripheral Nerve Society.)

Introduction: Numerous cases have been reported of patients with symptoms of Guillain-Barré syndrome associated with COVID-19, but much information is still lacking on this association and its implications. The objective of this review is to analyse the available evidence on this topic in the adult population., Material and Methods: A systematic review was conducted of studies published on scientific databases: PubMed, Cochrane, Science Direct, Medline, and WHO COVID-19 database., Results: We identified 47 studies, which were analysed and completed using the Covidence platform; the final analysis included 24 articles, with a total of 30 patients., Conclusions: We found a strong association between both conditions; furthermore, the studies analysed highlight differences in the presentation of the disease, with greater severity of symptoms in Guillain-Barre syndrome associated with COVID-19., (Copyright © 2020 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Numerous cases have been reported of patients with symptoms of Guillain-Barré syndrome associated with COVID-19, but much information is still lacking on this association and its implications. The objective of this review is to analyse the available evidence on this topic in the adult population., Material and Methods: A systematic review was conducted of studies published on scientific databases: PubMed, Cochrane, Science Direct, Medline, and WHO COVID-19 database., Results: We identified 47 studies, which were analysed and completed using the Covidence platform; the final analysis included 24 articles, with a total of 30 patients., Conclusions: We found a strong association between both conditions; furthermore, the studies analysed highlight differences in the presentation of the disease, with greater severity of symptoms in Guillain-Barre syndrome associated with COVID-19., (© 2020 Sociedad Española de Neurología. Published by Elsevier España, S.L.U.)

Introduction: Since February 2020, the outbreak of COVID-19 in Italy has forced the health care system to undergo profound rearrangements in its services and facilities, especially in the worst-hit areas in Northern Italy. In this setting, inpatient and outpatient services had to rethink and reorganize their activities to meet the needs of patients during the "lockdown". The Italian Association of Myology developed a survey to estimate the impact of these changes on patients affected by neuromuscular disorders and on specialized neuromuscular centers during the acute phase of COVID-19 pandemic., Methods: We developed an electronic survey that was sent to neuromuscular centers affiliated with the Italian Association of Myology, assessing changes in pharmacological therapies provision, outpatient clinical and instrumental services, support services (physiotherapy, nursing care, psychological support) and clinical trials., Results: 40% of surveyed neuromuscular centers reported a reduction in outpatient visit and examinations (44.5% of centers in Northern regions; 25% of centers in Central regions; 50% of centers in Southern regions). Twenty-two% of centers postponed in-hospital administration of therapies for neuromuscular diseases (23.4% in Northern regions; 13.0% in Central regions; 20% in Southern regions). Diagnostic and support services (physiotherapy, nursing care, psychological support) were suspended in 57% of centers (66/43/44% in Northern, Central and Southern centers respectively) Overall, the most affected services were rehabilitative services and on-site outpatient visits, which were suspended in 93% of centers. Strategies adopted by neuromuscular centers to overcome these changes included maintaining urgent on-site visits, addressing patients to available services and promoting remote contact and telemedicine., Conclusions: Overall, COVID-19 pandemic resulted in a significant disruption of clinical and support services for patients with neuromuscular diseases. Despite the efforts to provide telemedicine consults to patients, this option could be promoted and improved further. A close collaboration between the different neuromuscular centers and service providers as well as further implementation of telehealth platforms are necessary to ensure quality care to NMD patients in the near future and in case of recurrent pandemic waves., (©2020 Gaetano Conte Academy - Mediterranean Society of Myology, Naples, Italy.)

Peripheral neuropathies associated with painful small fiber neuropathy (SFN) are complex conditions, resistant to treatment with conventional medications. Previous clinical studies strongly support the use of dietary agmatine as a safe and effective treatment for neuropathic pain. Based on this evidence, we conducted an open-label consecutive case series study to evaluate the effectiveness of agmatine in neuropathies associated with painful SFN (Study Registry: ClinicalTrials.gov, System Identifier: NCT01524666). Participants diagnosed with painful SFN and autonomic dysfunctions were treated with 2.67 g/day agmatine sulfate (AgmaSet ® capsules containing G-Agmatine ® brand of agmatine sulfate) for a period of 2 months. Before the beginning (baseline) and at the end of the treatment period, participants answered the established 12-item neuropathic pain questionnaire specifically developed to distinguish symptoms associated with neuropathy and to quantify their severity. Secondary outcomes included other treatment options and a safety assessment. Twelve patients were recruited, and 11 patients-8 diagnosed with diabetic neuropathy, two with idiopathic neuropathy and one with inflammatory neuropathy-completed the study. All patients showed improvement in neuropathic pain to a varied extent. The average decrease in pain intensity was 26.0 rating points, corresponding to a 46.4% reduction in overall pain ( p < 0.00001). The results suggest that dietary agmatine sulfate has a significant effect in reducing neuropathic pain intensity associated with painful SFN resistant to treatment with conventional neuropathic pain medications. Larger randomized placebo-controlled studies are expected to establish agmatine sulfate as a preferred treatment.

Immune-mediated neuropathies (IMNs) following hematopoietic stem cell transplantation have been described recently, which, excluding Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, may present with atypical patterns. This retrospective, nested, case-control study reviewed data from 3858 patients who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) during the past 10 years at a single center, and 40 patients (1.04%) with IMN following haplo-HSCT were identified. Chronic graft-versus-host disease (cGVHD) (P = .043) and cytomegalovirus (CMV) viremia (P = .035) were recognized as independent risk factors for the development of IMN after haplo-HSCT. There were no significant differences in overall survival (P = .619), disease-free survival (P = .609), nonrelapse mortality (P = .87), or the incidence of relapse (P = .583) between patients with and without IMN after haplo-HSCT. However, patients with post-transplant IMN were at higher risk of developing cGVHD (P = .012) than patients who did not develop IMN. Twenty-four of the 40 patients with IMN (60%) attained neurologic improvement after treatments including vitamins B 1 and B 12 and/or immunomodulatory agents. However, 19 (47.5%) patients still had persistent motor/sensory deficits despite receiving timely treatment. More studies are needed to help develop standardized diagnostic and therapeutic strategies for patients with post-transplant IMN., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: The present study aims to determine the incidence and prevalence of trigeminal neuralgia (TN) in study population and difference in prevalence of TN in urban and rural population., Materials and Methods: This retrospective study includes 1215 study participants with typical idiopathic TN. Data regarding the age of onset, gender, site of involvement, and clinical presentations were retrieved from clinical records of patients reported from January 2011 to January 2018., Results: The study population consists of 1215 study participants aged between 21 and 87 years, with a mean age of 50.62 ± 15.872 years. The mandibular nerve is involved in most of the cases (56.9%), followed by maxillary nerve (42%). The right side of the face (57.1%) is more involved than the left side (38.8%). TN was more prevalent (52.4%) in rural population than urban population (47.6%)., Conclusion: TN is more common in females than males, the right side of the face is more involved than the left side, and it is more commonly found in rural population than urban population., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 National Journal of Maxillofacial Surgery.)

Background: In recent years the treatment of many tumor entities has been revolutionized by the use of modern immunotherapies with checkpoint inhibitors; however, good response rates are contrasted by many immune-mediated side effects. Neurological immune-mediated side effects are rare but often severe complications of checkpoint inhibitor treatment., Method: A systematic search in the PubMed and Web of Sciences databases was carried out for case reports and studies on neurological side effects during checkpoint inhibitor treatment., Results: A total of 42 articles on neurological side effects of checkpoint inhibitors with a total of 85 reported cases could be identified. The most frequently reported neurological side effects were myopathies, neuropathies, diseases of the neuromuscular endplates and encephalitides. Among those, encephalitides and myopathies with accompanying myocarditis were associated with the highest morbidity and mortality., Conclusion: Against the background of a rapidly increasing use of checkpoint inhibitors, this article provides an overview of currently available reports on the clinical courses of neurological side effects. Controlled studies on the treatment of neurological side effects are lacking. From case studies it can be assumed that early steroid treatment increases the probability of a complete remission of neurological symptoms. Typical symptom constellations must therefore be rapidly recognized and an immunosuppressive treatment must be initiated.

Neuropathies are very common in the population over 65 years old and their prevalence increases with age. The prevalence of polyneuropathies is about 7% in the elderly. However, other possible neuropathies should not be overlooked. Diabetes mellitus is the first cause of neuropathy in the world. Beyond 80 years-old, the risk of finding no etiology is about 40% but it implies a minimum initial explorations. A vitamin deficiency, a dysimmune or even hereditary cause should be eliminated in the elderly subject, keeping in mind the characteristics of age. We propose a review of the different forms of neuropathies by emphasizing the clinical or electrophysiological particularities of the elderly.

Mycoplasma pneumoniae is mainly recognized as a respiratory pathogen, although it is associated with the development of several extra-respiratory conditions in up to 25% of the cases. Diseases affecting the nervous system, both the peripheral (PNS) and the central nervous system (CNS), are the most severe. In some cases, particularly those that involve the CNS, M. pneumoniae -related neuropathies can lead to death or to persistent neurologic problems with a significant impact on health and a non-marginal reduction in the quality of life of the patients. However, the pathogenesis of most of the M. pneumoniae -related neuropathies remains undefined. The main aim of this paper is to discuss what is presently known regarding the pathogenesis and treatment of the most common neurologic disorders associated with M. pneumoniae infection. Unfortunately, the lack of knowledge of the true pathogenesis of most of the cases of M. pneumoniae -mediated neurological diseases explains why treatment is not precisely defined. However, antibiotic treatment with drugs that are active against M. pneumoniae and able to pass the blood-brain barrier is recommended, even though the best drug, dosage, and duration of therapy have not been established. Sporadic clinical reports seem to indicate that because immunity plays a relevant role in the severity of the condition and outcome, attempts to reduce the immune response can be useful. However, further studies are needed before the problem of the best therapy for M. pneumoniae -mediated neurological diseases can be efficiently solved.

Objective: The Erasmus Guillain Barre Outcome Score (EGOS) is a prognostic model that predicts the chance of being able to walk independently at 6 months after Guillain Barré syndrome (GBS). This study was conducted aiming to determine the validity of EGOS in a Brazilian population., Material and Methods: Data collected from GBS patients in Rio Grande do Norte, Brazil, were used to determine the validity of EGOS. GBS disability score was assessed in the second week of disease and at 6 months., Results: A total of 206 subjects were studied. The Brazilian patients were younger, with a more severe clinical presentation, with higher percentage of cranial nerve involvement and upper respiratory infection. There was no difference relative to sex or presence of anti-gangliosides antibodies. The demyelinating variant was more common (73.9%). However, only 24% of the Brazilians with EGOS 5.5-7 were not able to walk after 6 months, compared to 52% to European Group. Nine patients (3.8%) presented nodopathies, of these four had an EGOS >5, but only one of the latter group was unable to walk after 6 months of GBS., Conclusions: Erasmus Guillain Barre Outcome Score was not a good predictor for the ability to walk after 6 months of GBS in Rio Grande do Norte, Brazil. Differences could be that the Brazilian GBS were younger, or alternatively, it could be due to a different infection profile or in the incidence of nodopathies., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Advanced glycation end products (AGE) contribute to the development of diabetes complications. Their accumulation in skin can be non-invasively assessed by measurement of skin autofluorescence (SAF). Our study investigated whether SAF correlates with measures of diabetic peripheral neuropathy (DPN)., Methods: In a multi-center study (8 centers), 497 consecutive individuals with diabetes mellitus were investigated. Forearm SAF was measured using the AGE Reader (Groningen, The Netherlands). DPN was assessed using the Toronto Clinical Neuropathy Score (TCNS), the Neuropathy Symptoms Score (NSS) and the Neuropathy Disability Score (NDS). RESULTS (MEAN ± SD): According to the TCNS, SAF (arbitrary units - AU) was increased in individuals with DPN (TCNS > 5): 2.59 ± 0.56 AU compared with those without DPN (TCNS ≤ 5): 2.45 ± 0.53 AU, (p = 0.04) and significantly increased with the severity of DPN (p = 0.028). Higher SAF was detected in individuals with neuropathic deficits (NDS > 2): 2.58 ± 0.56 AU vs. those without deficits (NDS ≤ 2): 2.45 ± 0.53 AU, (p = 0.009) as well as in individuals with symptoms (NSS > 2): 2.54 ± 0.56 AU vs. those without symptoms (NSS ≤ 2): 2.40 ± 0.47 AU, (p = 0.022)., Conclusions: Accumulation of AGE in skin is increased in individuals with DPN and progresses with the severity of DPN. Therefore, SAF measurement, an easy-to-use, quick and non-invasive method, might help in identifying subjects at high risk for having DPN., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Herpes zoster (HZ) infection occurs in approximately 10% to 30% of individuals. Visceral neuropathies secondary to HZ can cause cystitis and urinary retention. But colonic pseudo-obstruction can also occur. Peripheral neuropathy may reveal segmental motor paresis of either upper or lower limbs, the abdominal muscles or the diaphragm. We report the case of a 62-year-old male patient who presented with abdominal distention and cutaneous vesicular eruption on the left side of the abdominal wall. Plain X-rays and computed tomography scan showed distended small bowel. A diagnosis of intestinal pseudo-obstruction was made secondary to segmental paresis of the small intestine and visceral neuropathy. Conservative management was successful and the patient was discharged uneventfully. Intestinal pseudo-obstruction ought to be considered when dealing with non-obstructive (adynamic) conditions of the digestive tract associated with HZ infection; since early recognition may help to avoid unnecessary surgery., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest.

Connexins (Cx) are largely represented in the central nervous system (CNS) with 11 Cx isoforms forming intercellular channels. Moreover, in the CNS, Cx43 can form hemichannels (HCs) at non-junctional membrane as does the related channel-forming Pannexin1 (Panx1) and Panx2. Opening of Panx1 channels and Cx43 HCs appears to be involved in inflammation and has been documented in various CNS pathologies. Over recent years, evidence has accumulated supporting a link between inflammation and cerebral neuropathies (migraine, Alzheimer's disease (AD), Parkinson's disease (PD), major depressive disorder, autism spectrum disorder (ASD), epilepsy, schizophrenia, bipolar disorder). Involvement of Panx channels and Cx43 HCs has been also proposed in pathophysiology of neurological diseases and psychiatric disorders. Other studies showed that following inflammatory injury of the CNS, Panx1 activators are released and prolonged opening of Panx1 channels triggers neuronal death. In neuropsychiatric diseases, comorbidities are frequently present and can aggravate the symptoms and make therapeutic management more complex. The high comorbidity between some neuropathies can be partially understood by the fact that these diseases share a common etiology involving inflammatory pathways and Panx1 channels or Cx43 HCs. Thus, anti-inflammatory therapy opens perspectives of targets for new treatments and could have real potential in controlling a cerebral neuropathy and some of its comorbidities. The purpose of this mini review is to provide information of our knowledge on the link between Cx43- and Panx-based channels, inflammation and cerebral neuropathies.

Background: Nerve conduction studies (NCSs) are essential for diagnosing various kinds of focal and diffuse neuropathies. Due to the paucity of local NCS data, electrodiagnostic laboratories in Punjab rely on values from Western and other Indian studies., Aim: This study was conducted to provide normative data for median nerve conduction parameters (motor and sensory) in Punjabi populace., Materials and Methods: A cross-sectional study was done on 290 participants (150 males and 140 females), aged 17-21 years, as per standardized protocol. The data were analyzed separately for both genders using SPSS version 20. It consisted of distal latencies and conduction velocities of motor and sensory divisions of median nerve. Student's unpaired t -test was used for statistical analysis., Results: There was no effect of gender on any of the median nerve conduction parameters. Height and weight had nonsignificant negative and positive correlation, respectively ( P > 0.05), with conduction velocity in both motor and sensory median nerves. For median motor nerve, the values of distal latency and conduction velocity in males were 2.9 ± 0.16 ms and 60.25 ± 2.99 m/s, respectively, whereas, in females, they were 2.6 ± 0.43 ms and 59.83 ± 2.82 m/s. Similarly, for median sensory nerve, the latency and velocity values in males were 2.8 ± 0.56 ms and 54.81 ± 3.70 m/s, whereas, in females, they were 2.4 ± 0.33 ms and 54.56 ± 3.65 m/s, respectively., Conclusion: The data in this study compared favorably with already existing data. It would help the local electrodiagnostic laboratories in assessing the median nerve abnormalities with greater accuracy in this population subset., Competing Interests: There are no conflicts of interest.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of several commonly used chemotherapy drugs including taxanes, vinca alkaloids, and platinum compounds. Development of CIPN is highly variable, both in self-reported symptoms and functional consequences, and can be severe enough to alter dose intensity., Purpose: To describe the natural histories of both patient-reported symptoms of CIPN and functional impairments in breast cancer patients undergoing taxane-based chemotherapy., Methods: Thirty-three breast cancer patients (32 female/1 male; 47.8 ± 11.2 years; n = 17 stage II/n = 16 stage III) were enrolled. Patients completed self-reports of symptoms and function (e.g., EORTC QLQ-CIPN20) and objective measures of physical function (i.e., balance and gait testing) in an outpatient oncology clinic at five timepoints: (1) baseline-prior to starting chemotherapy, (2-4) before starting subsequent chemotherapy cycles, and (5) 1-3 months after receiving their last taxane infusion., Results: Significant negative changes in both patient-reported outcomes and objective functional measures were observed. Decreased balance was observed after the first chemotherapy cycle (28% increase in medial-lateral excursion of the center of pressure, p = 0.016) and progressed with cumulative exposure (43% increase, p < 0.001). Patients also demonstrated slower walking speeds (5% decrease, p = 0.003) as they progressed through treatment. These functional deficits were mirrored with increased patient-reported symptom severity for all EORTC QLQ-CIPN20 subscales (all p < 0.05)., Conclusion: This study longitudinally assessed patient-reported outcomes concurrently with balance and gait testing in patients undergoing taxane therapy. Taxane treatment was associated with the development of clinically relevant problems in both CIPN symptoms and patient function.