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Background: Diabetic peripheral neuropathy (DPN) occurs in >50% of diabetic patients and is a high risk‐factor of balance problems and risk of falls. Impaired balance can lead to reduced function, which has a detrimental effect on patients' quality of life. Structured strength and balance training can result in sustained improvements in muscle strength, coordination, balance, functional status and quality of life. Objective: To determine the combined effects of strength and balance training versus aerobic training on balance, severity of symptoms of DPN, and quality of life in patients with DPN. Methods: This double blinded, two arm parallel design Randomized Clinical Trial. The study was conducted from March to December 2020 in the AIMS diabetic center Peshawar, Pakistan. Participants were selected through convenience sampling technique and randomly allocated into strength plus balance and aerobic training groups. Type 2 diabetic patients of both sexes, aged 40 to 80 years, with a Toronto neuropathy score ≥6 recruited, while patients with ulceration/infection of feet, medical/Surgical conditions, and non‐ambulatory patients were excluded from this study. Intervention was applied 3 days a week for 8 weeks. The Toronto clinical neuropathy system was used to assess neuropathy severity, SF‐36 to assess quality of life and the Berg balance scale was used for assessment of balance. Assessment was done at the baseline and after 8 weeks of intervention using SPSS. Version 22 was used for analysis. Results: The mean age of the participants was 60.80 ± 9.73. Between group analysis, which showed were statistically insignificant for neuropathy severity, balance and all domains of quality of life (p‐value >0.05) except SF‐36 General Health Perception Score, with Mean ± SD of 62.50 ± 7.54 in group A versus Mean ± SD of in group B 60.00 ± 15.98 (p‐value = 0.05). Within group analysis showed statistically significant results for neuropathy severity, balance and all domains of quality of life (p‐value<0.05). Conclusion: This study concluded that there is a statistically significant effect of structured balance and strength training and aerobic training on severity of DPN, balance and quality of life. But there was no statistically significant difference in improvement between the two intervention groups. [ABSTRACT FROM AUTHOR]

As one of the most common otologic diseases in the elderly, age‐related hearing loss (ARHL) usually characterized by hearing loss and cognitive disorders, which have a significant impact on the elderly's physical and mental health and quality of life. However, as a typical disease of aging, it is unclear why aging causes widespread hearing impairment in the elderly. As molecular biological experiments have been conducted for research recently, ARHL is gradually established at various levels with the application and development of integrated multi‐omics analysis in the studies of ARHL. Here, the recent progress in the application of multi‐omics analysis in the molecular mechanisms of ARHL development and therapeutic regimens, including the combined analysis of different omics, such as transcriptome, proteome, and metabolome, to screen for risk sites, risk genes, and differences in lipid metabolism, etc., is outlined and the integrated histological data further promote the profound understanding of the disease process as well as physiological mechanisms of ARHL. The advantages and disadvantages of multi‐omics analysis in disease research are also discussed and the authors speculate on the future prospects and applications of this part‐to‐whole approach, which may provide more comprehensive guidance for ARHL and aging disease prevention and treatment. [ABSTRACT FROM AUTHOR]

Longitudinal changes in neurofilament light chain (NfL) levels were evaluated alongside prespecified clinical assessments 24 months into the patisiran Global open-label extension (OLE) study in patients with ATTRv amyloidosis with polyneuropathy. All patients enrolled in the Global OLE, from phase III APOLLO and phase II OLE parent studies, received patisiran. Assessments included measures of polyneuropathy (modified Neuropathy Impairment Score+7 (mNIS+7)), quality of life (QOL; Norfolk QOL-Diabetic Neuropathy questionnaire (Norfolk QOL-DN)), and plasma NfL. Patients receiving patisiran in the parent study (APOLLO-patisiran, n = 137; phase II OLE-patisiran, n = 25) demonstrated sustained improvements in mNIS+7 (mean change from parent study baseline (95% confidence interval): APOLLO-patisiran −4.8 (−8.9, −0.6); phase II OLE-patisiran −5.8 (−10.5, −1.2)) and Norfolk QOL-DN (APOLLO-patisiran −2.4 (−7.2, 2.3)), and maintained reduced NfL levels at Global OLE 24 months. After initiating patisiran in the Global OLE, APOLLO-placebo patients (n = 49) demonstrated stabilized mNIS+7, improved Norfolk QOL-DN, and significantly reduced NfL levels. Patisiran continued to demonstrate an acceptable safety profile. Earlier patisiran initiation was associated with a lower exposure-adjusted mortality rate. Long-term patisiran treatment led to sustained improvements in neuropathy and QOL, with NfL demonstrating potential as a biomarker for disease progression and treatment response in ATTRv amyloidosis with polyneuropathy. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The pathoetiology and treatment of levator ani syndrome (LAS) remain unclear. METHODS: We evaluated pathophysiology using translumbosacral motor-evoked potentials and anorectal manometry in patients with LAS and compared with healthy controls. A cohort underwent translumbosacral neuromodulation therapy (TNT). RESULTS: Lumbar and sacral motor-evoked potential latencies were prolonged in 32 patients with LAS compared with 31 controls (P < 0.013), with higher prevalence of anal neuropathy (P 5 0.026). TNT improved anorectal pain (P 5 0.003) and neuropathy (P < 0.02) in 13 patients with LAS. DISCUSSION: Patients with LAS demonstrate significant lumbosacral neuropathy that may cause anorectal pain. TNT improved anorectal pain and neuropathy, providing a novel therapeutic option. [ABSTRACT FROM AUTHOR]

Introduction: Nepal is a developing country where diabetes is becoming a major health challenge due to its high prevalence of 8.5% affecting around 2 million people. Due to limited resources, there are many barriers to providing affordable and convenient diabetes care or regular screening for complications. There is no reliable data on incidence, prevalence, and complications of diabetic foot problems in Nepal. Methods: We conducted an online survey amongst senior physicians, who were members of 'Diabetes & Endocrine Association of Nepal' to assess their perception of diabetic foot problems in Nepal. Results: Thirty-Eight physicians responded to the survey who saw a total of 17597 patients in the preceding month. They recalled seeing 647 with 'Diabetic Foot Ulcers', giving a crude Diabetic Foot Ulcer prevalence rate of 3.7%. They recalled seeing 2522 patients with painful neuropathy that required medical treatment, giving a crude painful neuropathy prevalence rate of 14.3%. A history of foot ulcer was present in an additional 578 patients. Previous minor amputation had been performed in 215 patients (1.2%) and major amputation in 135 patients (0.8%). Discussion: Despite having expertise in various fields there is no dedicated multidisciplinary diabetic foot clinic in Nepal. This survey shows that diabetic foot problems are abundant in Nepal and there is a need for structured multidisciplinary approach for screening and treatment. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy (LHON) is a disease that affects the optical nerve, causing visual loss. The diagnosis of LHON is mostly defined by the identification of three pathogenic variants in the mitochondrial DNA. Idebenone is widely used to treat LHON patients, but only some of them are responders to treatment. In our study, we assessed the maximal respiration rate (MRR) and other respiratory parameters in eight fibroblast lines from subjects carrying LHON pathogenic variants. We measured also the effects of idebenone treatment on cell growth and mtDNA amounts. Results showed that LHON fibroblasts had significantly reduced respiratory parameters in untreated conditions, but no significant gain in MRR after idebenone supplementation. No major toxicity toward mitochondrial function and no relevant compensatory effect in terms of mtDNA quantity were found for the treatment at the tested conditions. Our findings confirmed that fibroblasts from subjects harboring LHON pathogenic variants displayed impaired respiration, regardless of the disease penetrance and severity. Testing responsiveness to idebenone treatment in cultured cells did not fully recapitulate in vivo data. The in-depth evaluation of cellular respiration in fibroblasts is a good approach to evaluating novel mtDNA variants associated with LHON but needs further evaluation as a potential biomarker for disease prognosis and treatment responsiveness. [ABSTRACT FROM AUTHOR]

Chronic Ataxic Neuropathy with anti-Disialosyl IgM Antibodies (CANDA) is a rare form of immune-mediated sensory ataxic neuropathy. We describe the case of a 45-year-old man, who was diagnosed with CANDA in October 2018. Since then, he has been treated with monthly courses of intravenous immunoglobulin administration (IV Ig) and, in October 2022, he underwent plasmapheresis, reporting a sudden worsening of clinical and motor picture. After a new IV Ig cycle admission, the patient was hospitalized to perform intensive rehabilitation, involving two individual sessions per day (90 minutes each) for 5 days a week. During hospitalization it was registered a relevant improvement in the muscle strength of the lower limbs (LLs). Furthermore, progressive improvements were recorded both in patient's motor performance and in his level of autonomy in activities of daily living. These results had a positive impact on his quality of life and made it possible to reduce the frequency of IV Ig treatments. This is the first case in literature reporting the combined effect of rehabilitation treatment and medical therapy in CANDA neuropathy. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is a common chronic inflammatory disorder occurring in genetically predisposed individuals secondary to gluten ingestion. CD usually presents with gastrointestinal symptoms such as pain, bloating, flatulence, and constipation or diarrhea. However, individuals can present in a nonclassical manner with only extraintestinal symptoms. The neurological manifestations of CD include ataxia, cognitive impairment, epilepsy, headache, and neuropathy. A lifelong gluten-free diet is the current recommended treatment for CD. This review discusses the relevant neurological manifestations associated with CD and the novel therapeutics. Further research is required to get a better understanding of the underlying pathophysiology of the neurological manifestations associated with CD. Clinicians should keep CD in the differential diagnosis in individuals presenting with neurological dysfunction of unknown cause. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma (PC) is an extremely rare disease. Although it may occasionally occur in genetic syndromes, it is more often sporadic. It is usually associated with a consistent secretion of PTH, causing severe hypercalcemia and potentially all clinical conditions due to primary hyperparathyroidism. Management of PC can be challenging: some clinical, biochemical, and radiological features may be useful, but the final diagnosis of malignancy strictly relies on histological criteria. To date, radical surgery is the firstchoice treatment and is the only effective therapy to control hypercalcemia and other clinical manifestations. On the other hand, chemo- or radiotherapy, local treatments, or novel drugs should be reserved for selected cases. We report an exceptionally unusual case of life-threatening PC, associated with several systemic manifestations: moderate pancreatitis, portal thrombosis, kidney stones, brown tumors, osteoporosis, hungry bone syndrome (HBS), chondrocalcinosis, neuropathy, and depression. The clinical case also represents an opportunity to provide a review of the recent literature, associated with a complete evaluation of the main diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Pain in the dentoalveolar region is a common symptom. This usually involves acute pain, meaning the correct treatment can be rapidly applied. However, for certain types of persistent pain in this region, the aetiology is difficult to determine. Previously, there has been confusion regarding the diagnosis and classification of this type of persistent pain, which was often designated under different terms, such as atypical odontalgia, phantom pain or deafferentation pain. Recently, a classification system was developed for these types of conditions and the following term was agreed: persistent dentoalveolar pain. This new term was the first step in arriving at an improvement in the taxonomy: three criteria were established to lead to advancements in the fields of clinical research and treatment. [ABSTRACT FROM AUTHOR]

Carpal tunnel syndrome (CTS) is a condition when median nerve, located in the carpal tunnel, is being suppressed by the surrounding structure. In 1854, the first clinical narration of median nerve compression in a carpal tunnel was found. CTS causes pain, tingling, and weakness in the half ring finger, middle finger, index finger, and thumb. These complaints lead the patients to seek medical help by a visiting doctor. CTS has become the major cause of upper extremity chronic neuropathic pain. CTS affects women 3.6 times more than men. This would cause high costs in medical treatment, rehabilitation, work hours lost compensation, initial pension costs, and new worker training. This makes CTS as a major problem in the field of employment. Carpal tunnel syndrome occurs as a result of chronic repetitive forceful work and other risk factors such as sex, age, heredity, hormonal, and weight. Knowledge of the diagnosis and comprehensive management of CTS are important to the doctor. Recent management based on the newest guidelines are important for clinician knowledge update. Correct diagnosis will lead to appropriate management based on recent CTS guidelines, which in turn will improve the quality of life for patients with CTS. This article will comprehensively discuss the diagnosis and recent management. [ABSTRACT FROM AUTHOR]

Peripheral nerve disorders are caused by a range of different aetiologies. The range of causes include metabolic conditions such as diabetes, obesity and chronic kidney disease. Diabetic neuropathy may be associated with severe weakness and the loss of sensation, leading to gangrene and amputation in advanced cases. Recent studies have indicated a high prevalence of neuropathy in patients with chronic kidney disease, also known as uraemic neuropathy. Immune-mediated neuropathies including Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy may cause significant physical disability. As survival rates continue to improve in cancer, the prevalence of treatment complications, such as chemotherapy-induced peripheral neuropathy, has also increased in treated patients and survivors. Notably, peripheral neuropathy associated with these conditions may be chronic and long-lasting, drastically affecting the quality of life of affected individuals, and leading to a large socioeconomic burden. This review article explores some of the major emerging clinical and experimental therapeutic agents that have been investigated for the treatment of peripheral neuropathy due to metabolic, toxic and immune aetiologies. [ABSTRACT FROM AUTHOR]

Treatment for Hodgkin lymphoma (HL) in adults comprises substantial risk of chemotherapy‐induced peripheral neurotoxicity. Here, we describe the case of patient with Charcot–Marie–Tooth disease or HSMN1 and advanced Hodgkin lymphoma undergoing treatment with modified BEACOPP achieving complete remission without major aggravation of neurological symptoms. [ABSTRACT FROM AUTHOR]

Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion, hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, [Formula: see text]-aminolaevulinic acid and porphyrins using a single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe, potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations in women, stress, alcohol and low-calorie diets, which should be avoided in patients where possible. For the management of attacks, intravenous hemin is approved, whereas new therapeutic approaches are currently being investigated as a baseline therapy for prevention of attacks and improvement of QoL. Among these, a novel siRNA-based agent, givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of variegate porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges, and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the efficacy and tolerability of diflunisal for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. Methods: We performed a retrospective longitudinal study of prospectively collected data for all domino liver transplant recipients with acquired amyloid neuropathy who received diflunisal at our hospital. Neurological deterioration was defined as an score increase of =2 points from baseline on the Neurological Impairment Scale/Neurological Impairment Scale-Lower Limbs. Results: Twelve patients who had received compassionate use treatment with diflunisal were identified, of whom seven had follow-up data for =12 months. Five patients (71.4%) presented with neurological deterioration on the Neurological Impairment Scale after 12 months (p = 0.0382). The main adverse effects were cardiovascular and renal, leading to diflunisal being stopped in five patients and the dose being reduced in two patients. Conclusion: Our study suggests that most domino liver transplant recipients with acquired amyloid neuropathy will develop neurological deterioration by 12 months of treatment with diflunisal. This therapy was also associated with a high incidence of adverse effects and low treatment retention. The low efficacy and low tolerability of diflunisal treatment encourage the search for new therapeutic options. [ABSTRACT FROM AUTHOR]

Dysthyroid optic neuropathy (DON) is a potentially sight-threatening eye disease associated with Graves' orbitopathy (GO). DON is not common in GO patients, reportedly occurring in only about 5% of patients. The pathogenesis of severe DON is considered to involve both muscular nerve strangulation and impaired blood flow. There is some objective grading of physical examination findings and the severity of GO, including a clinical activity score (CAS) and EUropean Group On Graves' Orbitopathy (EUGOGO), but no specialized protocol completely characterizes DON. Most clinicians have decided that the combination of clinical activity findings, including visual acuity, color vision, and central critical fusion frequency, and radiological findings, including magnetic resonance imaging (MRI), can be used to diagnose DON. MRI has the most useful findings, with T2-weighted and fat-suppressed images using short-tau inversion recovery (STIR) sequences enabling detection of extraocular changes including muscle and/orbital fat tissue swelling and inflammation and, therefore, disease activity. The first-choice treatment for DON is intravenous administration of steroids, with or without radiotherapy. Unfortunately, refractoriness to this medical treatment may indicate the need for immediate orbital decompression within 2 weeks. Especially in the acute phase of DON, thyroid function is often unstable, and the surgeon must always assume the risk of general anesthesia and intra- and post-operative management. In addition, there are currently many possible therapeutic options, including molecular-targeted drugs. The early introduction and combination of these immunomodulators, including Janus kinase inhibitors and insulin-like growth factor-1 receptor antibody (teprotumumab), may be effective for GO with DON. However, this is still under investigation, and the number of case reports is small. It is possible that these options could reduce systemic adverse events due to unfocused glucocorticoid administration. The pathophysiology of DON is not yet fully understood, and further studies of its treatment and long-term visual function prognosis are needed. [ABSTRACT FROM AUTHOR]

Methanol-induced optic neuropathy (Me-ION) is a serious condition that may result in long-term or irreversible visual impairment or even blindness secondary to damage and loss of function of the optic nerve and retina. Me-ION shows a tendency to occur as mass poisonings around the world with a clear predilection for poor societies in developing countries. The main mechanism underlying the molecular basis of Me-ION is the inhibition of the mitochondrial oxidative phosphorylation process through the binding of the toxic metabolite of methanol—formic acid—with the key enzyme of this process—cytochrome c oxidase. However, other mechanisms, including damage to the eye tissues by oxidative stress causing the intensification of the oxidative peroxidation process with the formation of cytotoxic compounds, as well as an increase in the synthesis of pro-inflammatory cytokines and influence on the expression of key proteins responsible for maintaining cell homeostasis, also play an important role in the pathogenesis of Me-ION. Histopathological changes in the eye tissues are mainly manifested as the degeneration of axons and glial cells of the optic nerve, often with accompanying damage of the retina that may involve all its layers. Despite the development of therapeutic approaches, persistent visual sequelae are seen in 30–40% of survivors. Thus, Me-ION continues to be an important problem for healthcare systems worldwide. [ABSTRACT FROM AUTHOR]

We present the case of an 8-year-old girl with chronic recurrent multifocal osteomyelitis (CRMO) involving the orbit and facial bone and causing left optic neuropathy. She presented with intermittent left periorbital swelling and a history of CRMO diagnosed 5 years earlier. Her disease responded well to adalimumab; however, delayed presentation resulted in permanent unilateral optic nerve atrophy and reduced vision. Orbital inflammatory disease is a rare manifestation of CRMO, and early recognition of the disease and treatment may prevent irreversible vision loss.▪ [ABSTRACT FROM AUTHOR]

Significance: Diabetes is a major source of neuropathy and neuropathic pain that is set to continue growing in prevalence. Diabetic peripheral neuropathy (DPN) and pain associated with diabetes are not adequately managed by current treatment regimens. Perhaps the greatest difficulty in treating DPN is the complex pathophysiology, which involves aspects of metabolic disruption and neurotrophic deficits, along with neuroimmune interactions. There is, therefore, an urgent need to pursue novel therapeutic options targeting the key cellular and molecular players. Recent Advances: To that end, cellular targeting becomes an increasingly compelling drug delivery option as our knowledge of neuroimmune interactions continues to mount. These nanomedicine-based approaches afford a potentially unparalleled specificity and longevity of drug targeting, using novel or established compounds, all while minimizing off-target effects. Critical Issues: The DPN therapeutics directly targeted at the nervous system make up the bulk of currently available treatment options. However, there are significant opportunities based on the targeting of non-neuronal cells and neuroimmune interactions in DPN. Future Directions: Nanomedicine-based agents represent an exciting opportunity for the treatment of DPN with the goals of improving the efficacy and safety profile of analgesia, as well as restoring peripheral neuroregenerative capacity. Antioxid. Redox Signal. 36, 122–143. [ABSTRACT FROM AUTHOR]

Keloids are scars that extend beyond the margins of an insulting cutaneous injury. Keloids are often thought to be primarily a cosmetic issue, as they are typically quite raised and pigmented. However, these scars also present with functional symptoms of pruritus and pain that significantly impact quality of life. The symptom of pruritus is frequently overlooked by dermatologists, and treatments are often primarily focused on the gross appearance of the scar. This review describes the prevalence and importance of pruritus in keloids. In addition, the putative mechanisms underlying the development of keloid pruritus, which include neuronal and immunological mechanisms, are discussed. Furthermore, this review describes keloid treatments that have been shown to reduce pruritus, treatments that specifically target the itch, and emerging therapies. [ABSTRACT FROM AUTHOR]

Keloids are scars that extend beyond the margins of an insulting cutaneous injury. Keloids are often thought to be primarily a cosmetic issue, as they are typically quite raised and pigmented. However, these scars also present with functional symptoms of pruritus and pain that significantly impact quality of life. The symptom of pruritus is frequently overlooked by dermatologists, and treatments are often primarily focused on the gross appearance of the scar. This review describes the prevalence and importance of pruritus in keloids. In addition, the putative mechanisms underlying the development of keloid pruritus, which include neuronal and immunological mechanisms, are discussed. Furthermore, this review describes keloid treatments that have been shown to reduce pruritus, treatments that specifically target the itch, and emerging therapies.

Acute and chronic immune-mediated neuropathies have been widely reported with medical intervention. Although causal relationship may be uncertain in many cases, a variety of drugs, several vaccination types, surgical procedures and bone marrow transplants have been reported as possible cause or trigger of a putative immune-mediated response resulting in acute and chronic neuropathies. We conducted a systematic review of the literature from 1966 to 2020 on reported cases of possible iatrogenic immune-mediated neuropathies. We determined in each case the likelihood of causality based on frequency of the association, focusing primarily on clinical presentation and disease course as well as available ancillary investigations (electrophysiology, blood and cerebrospinal fluid and neuropathology). The response to immunotherapy and issue of re-exposure were also evaluated. We also considered hypothesised mechanisms of onset of immune-mediated neuropathy in the specific iatrogenic context. We believe that a likely causal relationship exists for only few drugs, mainly antitumour necrosis factor alpha agents and immune checkpoint inhibitors, but remains largely unsubstantiated for most other suggested iatrogenic causes. Unfortunately, given the lack of an accurate diagnostic biomarker for most immune-mediated neuropathies, clinical assessment will often override ancillary investigations, resulting in lower levels of certainty that may continue to cast serious doubts on reliability of their diagnosis. Consequently, future reports of suspected cases should collect and exhaustively assess all relevant data. At the current time, besides lack of evidence for causality, the practical implications on management of suspected cases is extremely limited and therapeutic decisions appear likely no different to those made in non-iatrogenic cases. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common primary brain tumour in adults. It's often rapid evolution requires a multidisciplinary management. Surgery, radiotherapy and Temozolomide are the first-line treatments. At the time of disease recurrence, few treatment options are available. Bevacizumab has been considered the breakthrough treatment for this disease by leading to improved progression-free survival. Optic neuropathy is an uncommon but well-documented complication of radiation therapy for brain tumours. Contrary to bevacizumab, its relationship with the occurrence of this side effect remains controversial at this stage and requires further studies. We report the case of a patient followed for recurrent glioblastoma who developed optic neuropathy after 18 months of treatment with bevacizumab. [ABSTRACT FROM AUTHOR]

Background: Mepolizumab is an option for add‐on therapy in cases of refractory or relapsing eosinophilic granulomatous polyangiitis (EGPA). However, it has not been fully investigated if add‐on mepolizumab is effective for active refractory or active relapsing EGPA patients with life‐ and/or organ‐threatening manifestations, especially with severe neuropathy. Case presentation: We herein report on a 63‐year‐old man with severe progressive neuropathy secondary to active relapsing EGPA. In this case, the optimal dose of glucocorticoids and cyclophosphamide could not be used because of glaucoma and signet ring cell carcinoma. Add‐on therapy of mepolizumab showed prompt immunological remission and marked improvement in neurological manifestations. Conclusions: Mepolizumab can be considered as an important induction therapy option for active relapsing or refractory EGPA. It has the potential to effectively improve neurological disturbances associated with severe neuropathy in EGPA. [ABSTRACT FROM AUTHOR]

Beta-thalassemia is a genetico-haematological disorder that affects the integrity, structure, and survival of red blood cells due to deleterious mutation in the ß-globulin chain of hemoglobin. Other than blood disorder, this condition gives rise to numerous neurological and haematophysiological conditions which have not been fully discussed yet. These conditions include extramedullary hematopoiesis, evoked potential (Sensory, Auditory and Visual), neuropathy and myopathy and predisposition to the hypercoagulable state leading to stroke. Moreover, most opted therapy to alleviate this condition intrigue neurotoxicity that requires clinician's round the clock attention. Beta thalassemia remains an incurable disease, and various therapies have been introduced to fulfill the body's blood requirement. But this condition implicitly gives rise to a damaging range of symptoms that cannot be overlooked. Therefore, our review encompasses all those anomalies associated with beta-thalassemia and its probable curative therapy. [ABSTRACT FROM AUTHOR]

There are diverse forms of rehabilitative techniques available to improve postural control in diabetic peripheral neuropathy but little is known about the efficacy of these techniques. The primary focus of this review is to find out the effectiveness of diverse rehabilitative interventions in improving postural control in type 2 induced diabetic peripheral neuropathy. Methods: Two reviewers independently scrutinized the included studies. The selected studies underwent quality assessment by PEDro scale. Randomized Controlled Trial (RCT) having a score of 4 or more were included in the review. A search was conducted in PUBMED, MEDLINE, CINAHL, EMBASE, PROQUEST, Science Direct, Cochrane Library, Physiotherapy Evidence Database (PEDro) and Google Scholar. The Medical Subject Headings (MeSH) related to the interventions were also taken into account. Results: A total of 563 studies were identified and finally 8 studies were included in the review process. The included studies were 3 in task-specific balance training, 1 in treadmill, 1 in strengthening, 2 in whole body vibration, and 1 study in pilates analyzing posture using static posturography. No RCTs were reportedly found under tai chi and yoga. Conclusions: Interventions related to task-specific approach in balance training, treadmill, strengthening, WBV showed improvement in static postural control. Intervention with pilates did not show any beneficial effects. However, there still remains a need for quality trials as the results of these studies were ambivalent in interpretation and quality of the studies were limited by small sample size and higher attrition rates. [ABSTRACT FROM AUTHOR]

There is a growing realization that many patients are incorrectly diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), with at least half of patients that carry a diagnosis of CIDP in the USA possibly having a different explanation for their neuropathy or having no neuropathy at all. Many misdiagnosed patients go on to receive costly and potentially harmful treatments for a disease that they do not have, while at the same time missing an opportunity to treat their true ailment. The cost of misdiagnosis on patients and society is not trivial. Many factors contribute to misdiagnosis. Particular points of vulnerability include the evaluation of "atypical" CIDP, interpretation of equivocal nerve conduction studies, over-reliance on elevations in cerebrospinal fluid protein concentration in indeterminate ranges, and placing excessive diagnostic weight on subjective changes following the initiation of immunotherapy. In addition to heighted awareness of the challenges, adherence to CIDP diagnostic guidelines, utilization of objective metrics to document clinical change, and referrals to CIDP centers of excellence are strategies that may improve diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Diabetes and diabetic complications are considered as leading causes of both morbidity and mortality in the world. Unfortunately, routine medical treatments used for affected patients possess undesirable side effects, including kidney and liver damages as well as gastrointestinal adverse reactions. Therefore, exploring the novel therapeutic strategies for diabetic patients is a crucial issue. It has been recently shown that melatonin, as main product of the pineal gland, despite its various pharmacological features including anticancer, anti-aging, antioxidant and anti-inflammatory effects, exerts anti-diabetic properties through regulating various cellular mechanisms. The aim of the present review is to describe potential roles of melatonin in the treatment of diabetes and its complications. [ABSTRACT FROM AUTHOR]

Background: Current options for Chagas' disease treatment are restricted to benznidazole and nifurtimox. To the best of our knowledge, no study has ever compared their tolerance in adults in a non-endemic country.Objectives: To compare the completion rates and drug tolerance in a cohort of patients treated according to current guidelines.Patients and Methods: We analysed the medical records of all Chagas' disease patients aged 18 years or over who started antiparasitic treatment at the Geneva University Hospitals, Switzerland, from 2008 to 2016. We recorded treatment duration and all adverse events.Results: We included 176 patients, 92 and 84 of whom received benznidazole or nifurtimox, respectively. The overall treatment completion rate was 62.5%, without a significant difference between the groups (P=0.436). Most patients (89.8%) suffered at least one adverse event. Those receiving nifurtimox had more events (6.2 versus 3.5, P<0.001). Mucocutaneous symptoms predominated in the benznidazole group, whereas digestive symptoms were most frequent with nifurtimox. Neuropsychiatric events frequently occurred in both groups, most notably in patients receiving nifurtimox. Arthralgia, dyspnoea, sensitive neuropathy and pruritus were independent predictors of treatment interruption.Conclusions: Currently recommended drug regimens for Chagas' disease are not well tolerated and entail frequent treatment discontinuation irrespective of the drug used. This highlights the need to improve treatment tolerance in adults with Chagas' disease with new therapeutic options. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy (LHON) and other genetic causes of visual loss are important clinical entities that can cause profound visual loss. To date, therapeutic options have been quite limited, but insights into the genetic basis of these diseases and advances in the ability to deliver effective and safe gene therapy have opened the door for new therapeutics that may revolutionize the approach to treating these conditions. This article reviews emerging gene therapies of LHON and other inherited ophthalmological diseases, addressing the technical, clinical, and ethical challenges that researchers and clinicians will encounter as new treatments become available for these conditions. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a devastating pain condition of cancer therapy that may force chemotherapy dose reduction or discontinuation. Since treatment options for CIPN are quite limited, we investigated the effect of 10% amitriptyline cream on neuropathic pain.Patients and Methods: This pilot study enrolled patients with hematological or solid tumors presenting hands and feet CIPN (for less than 1 month without previous treatment for CIPN [Group 1]; for more than 1 month with previous treatment [Group 2]). Patients applied 10% amitriptyline cream twice a day. Pain intensity was evaluated at 1, 2, and 4 weeks then monthly up to 1 year. The primary endpoint was change from baseline to 4-week treatment in median pain score assessed by visual analogue scale (VAS).Results: Overall, 44 patients were enrolled. Median (range) age was 67 (46-80) years, 34% were female. The majority (88.6%) had hematological malignancies, and the most commonly used chemotherapeutic agents were bortezomib and oxaliplatin. The median (range) VAS pain score decreased from 7 (4-9) at baseline to 2 (0-4) after 4-week topical treatment. No difference was seen between Group 1 and Group 2. Reduced initial chemotherapy doses in 11 patients as well as chemotherapy discontinued in 5 patients at baseline were resumed after treatment with 10% amitriptyline cream.Conclusion: Considering the limited efficacy of conventional systemic treatments in CIPN and their safety profile, 10% topical amitriptyline appears to be a good candidate for first-line CIPN therapy, allowing continuation of chemotherapy at effective doses. The results are worth to be confirmed in a placebo-controlled clinical trial. [ABSTRACT FROM AUTHOR]