Structural impairment patterns in peripapillary retinal fiber layer and retinal ganglion cell layer in mitochondrial optic neuropathies

AIM：To evaluate the structural injure patterns in peripapillary retinal fiber layer （pRNFL）, retinal ganglion cell layer （RGCL） and their correlations to visual function in various mitochondrial optic neuropathies （MON） to offer help to their differential diagnosis.METHODS：Totally 32 MON patients （60 eyes） were recruited within 6mo after clinical onsets, including 20 Leber hereditary optic neuropathy （LHON） patients （37eyes）, 12 ethambutol-induced optic neuropathy （EON）patients （23 eyes）, and 41 age-gender matched healthy controls （HC, 82 eyes）. All subjects had pRNFL and RGCL examinations with optic coherence tomography （OCT） and visual function tests.RESULTS：In the early stages of MON, the temporal pRNFL thickness decreased （66.09±22.57μm）, but increased in other quadrants, compared to HC （76.95±14.81μm）. The other quadrants remaining stable for LHON and EON patients besides the second hour sector of pRNFL thickness reduced and the temporal pRNFL decreased （56.78±15.87μm） for EON. Total macular thickness in MON reduced remarkably（279.25±18.90μm; P=0.015）, which mainly occurring in the inner circle （3 mm diameter of circle） and the nasal temporal sectors in the outer circle （5.5 mm diameter of circle）, in contrast to those in HC. RGCL thickness reduced in each sector of the macula （61.90±8.73μm; P≤0.001）. It strongly showed the correlationship of best corrected visual acuity （R=0.50, P=0.0003） and visual field injury （R=0.54,P=0.0002） in MON patients.CONCLUSION：OCT is a potential tool for detecting structural alterations in the optic nerves of various MON. Different types of MON may have different damage patterns.

ROCK inhibition as a novel potential strategy for axonal regeneration in optic neuropathies

Optic neuropathies or optic nerve diseases are a frequent cause of permanent vision loss that can occur after inflammation,ischemia,infection,tumors,trauma and/or an elevated pressure inside the eye（also called intraocular pressure or IOP）.

Retinal nerve fiber and ganglion cell layer thinning in hereditary and acquired mitochondrial optic neuropathies

Dear Editor,With interest we read the article by Teng et al[1]about a study of the retinal nerve and ganglion cell layers by means of optic coherence tomography(OCT)in 32 patients with a mitochondrial optic neuropathy(MON).Included were 20 patients with hereditary MON[Leber’s hereditary optic neuropathy(LHON)],12 patients with acquired MON[ethambutol-induced optic neuropathy(EION)],and 41 healthy controls.Retinal nerve fiber layer(RNFL)thickness was reduced in the nasal,superior,temporal,and inferior quadrants in LHON patients but only in the temporal quadrant in the EION patients.Thickness of the retinal ganglion cell layer(RGCL)was similarly reduced in LHON and EION patients.We have the following comments and concerns.

Cellular reprogramming and inherited peripheral neuropathies: perspectives and challenges

Inherited peripheral neuropathies （or Charcot-Marie-Tooth disease, CMT） are a phenotypically and genetically heterogeneous group of disorders, which are currently untreatable. They are the most common inherited neuromuscular disorder, affecting around 1 in every 2,500 people （over 120,000 people in the US）. Based on clinical neurophysiological and histopathological features, inherited neuropathies can be divided into two major forms： demyelinating （type 1） and axonal （type 2） CMT （Saporta, 2014）.

Demonstration of reversible retinal ganglion cell dysfunction in inflammatory optic neuropathies utilizing pattern electroretinography

Dear Editor,I am Dr.Austin Bach from Larkin Community Hospital in South Miami,Florida,USA.I am writing to you to present three cases of inflammatory optic neuritis that was followed to resolution using pattern electroretinography（PERG）.

Neurorestoration from medicinal plants:an opportunity to treat painful neuropathies

Neuropathic pain originates from damages to the somatosensory nervous system（IASP-International Association for the Study of Pain-taxonomy）.Lesions（traumas,compression,iatrogenic and pharmacological causes）or diseases（infections,diabetes,ischemia,cancer）lead to the establishment of hypersensitivity.

Clinical analysis of symmetry peripheral entrapment neuropathies of upper extremity

Objective To discuss the etiology,course of diseases and prognosis of symmetry peripheral entrapment enuropathies of upper extremity. Methods The etiology, clinical scale and resluts of 14 cases were analyzed betwen 1999 and April 2002. Results In the bilateral tunnel syndrome, the excellent and good rate was 60% at the original side and 80% at the contralateral side occurred later. In the bilateral carpal tunnel syndrome, the excellent and good rate was 67% at the original side and 89% at the contralateral side occurred later. Conclusion The main etiological factor of the bilateral cubital tunnel syndrome was the elbow eversion deformity. The lesions of synovium contributed mainly to the symmetry carpal tunnel syndrome. The symmetry peripheral entrapment neuropathies of upper extremity should be operated on as soon as possible when diagnosis had been made for enhancement of treatment outcome. 5 refs,2 tabs.

Entrapment neuropathies in diabetes mellitus

Neuropathy is a common complication of diabetes mellitus(DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies(EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmarkof peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM,particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism,the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage,making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features.

Peripheral Neuropathies Revealing Gougerot-Sjögren’s Syndrome: Description of 3 Cases

Introduction: Sjögren’s syndrome is an autoimmune epithelitis with various extraglandular signs, among which are neurological, with a variable frequency according to studies. We report three cases of peripheral neuropathy revealing Gougerot-Sjögren’s syndrome, collected in the Neurology Department of the Fann University Hospital in Dakar (Senegal). Observations: The first patient, aged 48 years, presented with a length-dependent sensitivomotor polyneuropathy associated with retrobulbar optic neuritis, with dry eyes and dry mouth noticed by the patient for several years. The second patient, aged 28 years, was admitted to the hospital with chronic generalized paresthesia in the context of xerostomia and xerophthalmia. The results of the clinical examination and the electroeneuromyogram were in favour of pure sensory neuronopathy. The third patient was 32 years old female, with a history of thyroidectomy and acute inflammatory demyelinating polyneuropathy (AIDP), who was seen for acute ascending flaccid tetraplegia with facial diplegia, preceded by diffuse paresthesia. The diagnosis of recurrence of acute demyelinating polyradiculonueropathy was retained in view of the rapidly increasing character of the deficit, the hyperproteinorachy at the lumbar puncture, and the signs of demyelination at the ENMG. The diagnosis of Gougerot-Sjögren’s syndrome in our three patients was established on the basis of the 2016 ACR/EULAR criteria. Indeed, the anti-SSA antibodies (Ro) were positive in our 3 patients with a biopsy of the salivary glands which showed stage 3 in the first patient and stage 4 in the two others. Corticosteroid therapy and immunosuppressive treatment resulted in a favourable clinical evolution on the neurological and general levels. Conclusion: Gougerot-Sjögren’s syndrome is an autoimmune exocrinopathy that may present with peripheral neuropathy, which may precede the diagnosis of Sjögren’s syndrome, be concomitant or occur during the course of the disease.

Cranial neuropathies in sarcoidosis

Sarcoidosis is a multisystem, chronic inflammatory disease that is characterized by the development of non-caseating granulomas in multiple body tissues and organ systems. Neurological complications of systemic sarcoidosis include peripheral and cranial neuropathies, myopathies, seizures, gait dysfunction, and cognitive decline. Because sarcoidosis has a predilection to involve the basilar meninges, cranial neuropathy is the most prevalent neurological deficit seen when the nervous system is involved. Sarcoidosis cranial neuropathy may occur at different stages of the disease and even as the initial clinical manifestation of central nervous system involvement. Attributing a cranial neuropathy to sarcoidosis can be challenging, particularly in the setting of normal imaging studies. In this review, cranial neuropathies in sarcoidosis are discussed in detail.

Ischemic optic neuropathies-update

This submission will briefly review the anatomy and physiology of the optic nerve,and highlight various ischemic optic neuropathies including anterior ischemic optic neuropathies(non-arteritis and arteritic),diabetic papillopathy,posterior ischemic optic neuropathies,and ischemic optic neuropathies in the setting of hemodynamic compromise.

Application of optical coherence tomography in hereditary,toxic and metabolic optic neuropathies

Hereditary,metabolic and toxic optic neuropathies cause bilateral,central vision loss and therefore can result in severe impairment in visual function.Accurate,early diagnosis is critical,as nutritional and toxic optic neuropathies may be reversible if identified early,and diagnosis of hereditary optic neuropathies can prevent unnecessary invasive workup,provide prognostic information,and allow for effective genetic counseling.Optical coherence tomography(OCT)is a valuable tool that aids in the diagnosis and prognostication of optic neuropathies as it allows for quantification of changes in the retinal ganglion cells(RGCs)and retinal nerve fiber layer(RNFL)over time.We review the characteristic clinical presentations of hereditary,metabolic and toxic optic neuropathies,with an emphasis on OCT findings.

Frequency, Risk Factors and Clinical Forms of Neuropathies in Diabetics in Hospitals in Burkina Faso

Introduction: Diabetic neuropathy is one of the most common chronic complications of diabetes. Most of the studies on the subject in the sub region, particularly in Burkina Faso, dealt it with the study of the complications of diabetes, or one of its components. Our study was designed to study in particular in all its aspects, by searching for its peculiarities in our context, for improvement of its support. Methodology: This is a cross-sectional descriptive study carried out in 150 diabetic patients aged at least 15 years followed in the Department of Internal Medicine at Yalgado Ouedraogo University Teaching Hospital. All patients included had agreed to participate in our survey after informed consent. We collected the data during the period from 2015 November to 2016 June. Each patient was evaluated by the DN4 questionnaire and clinically by a neurological examination. We determinated the frequency, the sociodemographic, clinical and therapeutic characteristics of diabetes neuropathy and its related factors. Results: The frequency of diabetic neuropathy was 80.7%. Peripheral neuropathies were seen in 81.8% of cases and autonomic neuropathies in 72.7% of cases. Autonomic neuropathy was dominated by the DAN (59.1%), and erectile dysfunction (44%). There was a high comorbidity with physical inactivity (66.9%), obesity (49.4%) and hypertension (38.8%). There were poorly controlled patients in 38.8%. A link was found between T2DM and neuropathy (p = 0.014). Painful diabetes was related to the quality of glycemic control (p = 0.007), and hypertension (p = 0.021). A link was also found between tobacco consumption (p < 0.001), male (p < 0.001), and urogenital autonomic neuropathy. Conclusion: Diabetic neuropathies are very common in our context and could be a haunting to the practitioner with the progression of diabetes and its corollary of degenerative complications. There was a significant association between Type 2 Diabetes mellitus and the presence of peripheral diabetic neuropathy.

Diabetic peripheral neuropathy and neuromodulation techniques:a systematic review of progress and prospects

Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and feet.The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this domain.The investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord stimulation.This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy.Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments.Through these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

Controversies in fecal incontinence

Fecal incontinence is a common condition that can significantly impact patients’quality of life.Obstetric anal sphincter injury and anorectal surgeries are common etiologies.Endoanal ultrasound and anorectal manometry are important diagnostic tools for evaluating patients.There are various treatment options,including diet,lifestyle modifications,drugs,biofeedback therapy,tibial and sacral nerve neuromodulation therapy,and surgery.In this editorial,we will discuss current controversies and novel approaches to fecal incontinence.Screening for asymptomatic anal sphincter defects after obstetric anal sphincter injury and in patients with inflammatory bowel disease is not generally recommended,but may be helpful in selected patients.The Garg incontinence score is a new score that includes the assessment of solid,liquid,flatus,mucous,stress and urge fecal incontinence.Novel tests such as translumbosacral anorectal magnetic stimulation and novel therapies such as translumbosacral neuromodulation therapy are promising diagnostic and treatment options,for both fecal incontinence and neuropathy.Home biofeedback therapy can overcome some limitations of the office-based therapy.Skeletal muscle-derived cell implantation of the external anal sphincter has been further studied as a possible treatment option.Sacral neuromodulation may be useful in scleroderma,congenital fecal incontinence and inflammatory bowel disease but merits further study.

Small cell lung cancer with peripheral neuropathy as the first symptom:Two case reports

BACKGROUND Small cell lung cancer(SCLC)is the most malignant type of lung cancer.Even in the latent period and early stage of the tumor,SCLC is prone to produce distant metastases with complex and diverse clinical manifestations.SCLC is most closely related to paraneoplastic syndrome,and some cases present as paraneoplastic peripheral neuropathy(PPN).PPN in SCLC appears early,lacks specificity,and often occurs before diagnosis of the primary tumor.It is easy to be misdiagnosed as a primary disease of the nervous system,leading to missed diagnosis and delayed diagnosis and treatment.CASE SUMMARY This paper reports two cases of SCLC with limb weakness as the first symptom.The first symptoms of one patient were rash,limb weakness,and abnormal electromyography.The patient was repeatedly referred to the hospital for limb weakness and rash for>1 year,during which time,treatment with hormones and immunosuppressants did not lead to significant improvement,and the condition gradually aggravated.The patient was later diagnosed with SCLC,and the dyskinesia did not worsen as the dermatomyositis improved after antineoplastic and hormone therapy.The second case presented with limb numbness and weakness as the first symptom,but the patient did not pay attention to it.Later,the patient was diagnosed with SCLC after facial edema caused by tumor thrombus invading the vein.However,he was diagnosed with extensive SCLC and died 1 year after diagnosis.CONCLUSION The two cases had PPN and abnormal electromyography,highlighting its correlation with early clinical indicators of SCLC.

Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

Autophagy-targeting modulation to promote peripheral nerve regeneration

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

Occupational Exposure to Municipal Solid Wastes and Development of Toxic Neuropathies:Possible Role of Nutrient Supplementation,Complementary and Alternative Medicines in Chemoprevention

Achieving effective municipal solid waste （MSW） management remains a major challenge and waste generation and accumulation continue to constitute important environmental and public health concern, particularly in most developing countries. Although the general population is at risk of adverse health consequences and hazards associated with exposure to MSW, the waste management workers （WMWs） are the most vulnerable because of their direct involvement in the disposal of waste, with increasing evidence of work-related health and safety risks among these individuals. Among the numerous work-related health hazards prevalent in WMWs, development of toxic neuropathies following chronic occupational exposure remains poorly recognized. However, the risk or predisposition to toxic neuropathies is becoming evident considering the increasing recognition of large amount of neurotoxic heavy metals and hazardous industrial materials present in MSW in mostparts of the world. The present review seeks to draw attention to the continuous vulnerability of the WMWs to developing toxic neuropathies. This is aimed at facilitating conscious efforts by relevant governmental and non- governmental agencies towards promoting risk reduction and ensuring adequate protection against possible toxic polyneuropathies associated with occupational exposure to solid wastes. While continuous education of the WMWs on the need for adequate compliance to safety regulations and practice remains sacrosanct towards achieving significant reduction in toxic neuropathies and related adverse health consequences of waste handling, it is also our intention in this review to underscore the possible relevance of nutrient supplementation and alternative medicines in chemoprevention.