ABSTRACT
Background@#Vitamin B12 is one of the common drugs used by physicians to treat peripheral neuropathy (PN), although many patients have a good response, however, overdose and toxicity aggravate the condition and worsen the patient’s symptoms. The purpose of this paper is to highlight association between Vitamin B12 toxicity and deterioration of PN symptoms.@*Case Summary@#An elder Sudanese man with acute onset of sensory PN, the patient’s symptoms started by tingling sensations and paresthesia affecting both hands and feet. After patient received cobalamin (vitamin B 12) prescribed by his doctor, the patient symptoms were markedly aggravated and his condition worsened to extend that impaired the normal patient ordinary work. No symptoms related to motor system. Other possible etiologies were studied and excluded. Investigations of his condition revealed blood level of B12 was 1900 pg/mL, the patient condition improved dramatically with discontinuation of the drug.@*Conclusion@#Cobalamin toxicity aggravate sensory PN symptoms. Clinicians are advised to adjust the dose and check Cobalamin level before and during treatment to avoid its toxicity.
Subject(s)
Peripheral Nervous System Diseases , Vitamin B 12ABSTRACT
Propósito: La neuropatía periférica tiene un espectro clínico inespecífico y multifactorial, con frecuente subdiagnóstico y terapéutica de eficacia variable. Existe una heterogénea prescripción de vitaminas B, las cuales pueden desempeñar un rol importante en el manejo de diferentes neuropatías; sin embargo, en Colombia no existen guías clínicas al respecto. El propósito de este trabajo es orientar en el reconocimiento temprano de las neuropatías periféricas y generar recomendaciones sobre el uso adecuado de vitaminas B neurotrópicas. Descripción de la metodología: Acuerdo de expertos sobre la neuropatía periférica y el rol terapéutico de las vitaminas B con énfasis en la epidemiología en Colombia, diagnóstico y tratamiento. Contenidos: En Colombia, la prevalencia de neuropatía periférica se estima cercana al 10 %, sin embargo, no hay datos recientes. Dentro de las etiologías más frecuentes se encuentran la neuropatía diabética, infecciosa, inflamatoria, carenciales, toxica y farmacológica. Se recomiendan las siguientes herramientas de tamizaje en población de riesgo: DN4, MNSI, test de monofilamento, test de vibración y valoración de reflejos. Las vitaminas B1, B6 y B12 son seguras, accesibles y pueden ser eficaces en neuropatía periférica, incluso cuando el déficit no ha sido demostrado, pero con requerimientos particulares en su administración conjunta. Conclusiones: Las neuropatías periféricas son un reto diagnóstico y terapéutico que requiere la identificación oportuna para el tratamiento de la etiología subyacente y el control de síntomas. El uso de vitaminas B neurotrópicas es efectivo y seguro en neuropatía periférica carencial, y también parece ser eficaz en el manejo de neuropatías periféricas de diferentes etiologías.
Purpose: Peripheral neuropathy has a nonspecific and multifactorial clinical spectrum, with frequent underdiagnosis and therapeutics of variable efficacy. There is a high but heterogeneous prescription of B vitamins, which can play an important role in the management of different neuropathies; however, in Colombia there are no clinical guidelines in this regard. The purpose of this article is to guide the early recognition of peripheral neuropathy and generate recommendations on the proper use of neurotropic B vitamins. Description of the methodology: Expert agreement on peripheral neuropathy and the therapeutic role of B vitamins with emphasis on epidemiology in Colombia, diagnosis and treatment. Contents: In Colombia, there are no recent data to estimate the prevalence of peripheral neuropathy; the main etiologies are: diabetes mellitus, nutritional deficiencies, herpes zoster and neuropathies due to chemotherapy. Given risk factors in the anamnesis, the use of DN4, MNSI, monofilament test, vibration test and assessment of reflexes is recommended. Vitamins B1, B6, and B12 are safe and can be effective in peripheral neuropathy, even when the deficit has not been demonstrated, but with special requirements in their joint administration. Conclusions: peripheral neuropathies are a diagnostic and therapeutic challenge, and require timely identification, for the treatment of the underlying etiology and symptom control. The use of neurotropic B vitamins is effective and safe in deficient peripheral neuropathy, and also appears to be effective in the management of peripheral neuropathies of different etiologies.
Subject(s)
Vitamin B 12 , Peripheral Nervous System Diseases , Diabetic Neuropathies , Diagnosis , Pyridoxine , Pain ManagementABSTRACT
This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.
Subject(s)
Humans , Blood Glucose , Diabetic Neuropathies/drug therapy , Drugs, Chinese Herbal/therapeutic use , Glycated Hemoglobin , Hypesthesia/drug therapy , Multicenter Studies as Topic , Pain/etiology , Treatment Outcome , Peripheral Nervous System Diseases/etiologyABSTRACT
OBJECTIVES@#To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN.@*METHODS@#The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups.@*RESULTS@#A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05).@*CONCLUSIONS@#There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.
Subject(s)
Child , Humans , Infant , Child, Preschool , Adolescent , Antineoplastic Agents, Phytogenic/adverse effects , Cohort Studies , Peripheral Nervous System Diseases/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Vincristine/adverse effectsABSTRACT
Abstract Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration- and time-dependent in both assays, since the lowest concentration tested (0.1mM) also caused significant cytotoxicity at 96h. N-acetyl-cysteine (1mM), a precursor of glutathione synthesis, prevented ADR-induced toxicity elicited by 0.5mM and 0.25mM ADR following a 96-h exposure, while the antioxidant Tiron (100µM) was non-protective. In conclusion, ADR led to mitochondrial distress and ultimately cell death in non-differentiated SH-SY5Y cells, possibly because of ADR oxidation products. The involvement of such processes in the catecholamine-induced peripheral neuropathy requires further analysis.
Subject(s)
Epinephrine/agonists , Peripheral Nervous System Diseases/classification , Toxicity , Neurons/classification , Peripheral Nerves/abnormalities , Bromides/antagonists & inhibitors , Oxidative Stress/drug effects , Antioxidants/pharmacologySubject(s)
Humans , Vaccines , Peripheral Nervous System Diseases , Guillain-Barre Syndrome , Immunization , VaccinationABSTRACT
Introducción: El SARS-CoV-2 afecta principalmente al sistema respiratorio, pero el daño producido por este virus también se extiende a otros sistemas, incluido el sistema nervioso, y los mecanismos de infección neurológica pueden ser directos o indirectos. Objetivo: Determinar la relación entre las manifestaciones neurológicas y la severidad de la enfermedad en pacientes sintomáticos positivos a la COVID-19. Hospital San Vicente de Paúl. 2021. Material y Métodos: Estudio observacional de corte transversal, empleando el registro de historias clínicas de los pacientes hospitalizados con la COVID-19 y manifestaciones neurológicas, las cuales se clasificaron en manifestaciones del sistema nervioso central y manifestaciones del sistema nervioso periférico. Resultados: 74,1 por ciento pacientes presentaron manifestaciones neurológicas, el mayor porcentaje se concentró en pacientes que desarrollaron enfermedad grave (15 [60 por ciento], SNC; 91 [77,1 por ciento], SNP; 125 [65,4 por ciento], SNC y SNP). La presencia conjunta de manifestaciones neurológicas centrales y periféricas se asoció significativamente con la COVID-19 crítica (P valor= 0,011; OR: 2,005). El índice de mortalidad alcanzó 2,69 por ciento. Conclusiones: Las manifestaciones neurológicas en pacientes hospitalizados con la COVID-19 son muy frecuentes, y la COVID-19 crítica tiene mayor probabilidad de presentar manifestaciones neurológicas(AU)
Introduction: SARS-CoV-2 mainly affects the respiratory system, but the damage caused by this virus also extends to other systems, including the nervous system, and the mechanisms of neurological infection can be direct or indirect. Objective: To determine the relationship between neurological manifestations and disease severity in symptomatic COVID-19 positive patients at San Vicente de Paul Hospital in 2021. Material and Methods: A cross-sectional observational study was conducted using medical records of patients hospitalized with COVID-19 and neurological manifestations, which were classified into manifestations of the central nervous system and manifestations of the peripheral nervous system. Results: The results show that 74,1 percent of patients presented neurological manifestations; the highest percentage was concentrated in patients who developed severe disease (15 [60 percent], CNS; 91 [77,1 percent], PNS; 125 [65,4 percent], CNS and PNS). The joint presence of central and peripheral neurological manifestations was significantly associated with critical COVID-19 (P value= 0,011; OR: 2,005). The mortality rate reached 2,69 percent. Conclusions: Neurological manifestations in hospitalized COVID-19 patients are very common, and critical COVID-19 is more likely to have neurological manifestations(AU)
Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Severity of Illness Index , Central Nervous System Diseases/complications , Peripheral Nervous System Diseases/complications , COVID-19/complications , Odds Ratio , Cross-Sectional Studies , COVID-19/mortality , Centenarians , Octogenarians , Oxygen Saturation , NonagenariansABSTRACT
SUMMARY: This study aims to investigate the effect of Tangzhouling on the morphological changes of Nissl bodies in the dorsal root ganglion of DM Rats. In this study, 69 rats were randomly divided into a control group (n = 10) and a model group (n = 59). The rats in the model group were randomly divided into a diabetic group (n = 11), a vitamin C group (n = 12), a low dose Tangzhouling group (n = 12), a medium dose Tangzhouling group (n = 12) and a high dose Tangzhouling group (n = 12). The dose of Tangzhouling in the low dose group was 5 times that of the adult dose, being 0.44g/kg/d. The dose of Tangzhouling in the medium dose group was 10 times that of the adult dose, being 0.88g/kg/d. The dose of Tangzhouling in the high dose group was 20 times that of the adult dose, being 1.75g/kg/d. All doses above are crude drug dosages. Rats in the vitamin C group were given 10 times the dose of an adult, being, 0.05 g/ kg/d. The diabetic group and the control group were given the same amount of distilled water. Drug delivery time is 16 weeks. The dorsal root ganglion was placed in a freezing tube at the end of the experiment. The morphological changes of Nissl bodies in the dorsal root ganglion were detected by HE and Nissl staining. The study results showed that vitamin C had no significant effect on the quantity, size and nucleolus. Tangzhouling can improvee the morphology, quantity and nucleolus of Nissl bodies to a certain extent, and the high dose is better than the lower dose. Tangzhouling capsules can improve the nerve function of DM rats through Nissl bodies.
RESUMEN: Este estudio tuvo como objetivo investigar el efecto de Tangzhouling en los cambios morfológicos de los cuerpos de Nissl en el ganglio de la raíz dorsal de las ratas DM. En este estudio, 69 ratas se dividieron aleatoriamente en un grupo control (n = 10) y un grupo modelo (n = 59). Las ratas del grupo modelo se dividieron aleatoriamente en un grupo diabéticos (n = 11), un grupo vitamina C (n = 12), un grupo de dosis baja de Tangzhouling (n = 12), un grupo de dosis media de Tangzhouling (n = 12) y un grupo de dosis alta de Tangzhouling (n = 12). La dosis de Tangzhouling en el grupo de dosis baja fue 5 veces mayor que la dosis del adulto, siendo 0,44 g/kg/d. La dosis de Tangzhouling en el grupo de dosis media fue 10 veces mayor que la dosis del adulto, siendo 0,88 g/kg/d. La dosis de Tangzhouling en el grupo de dosis alta fue 20 veces mayor que la dosis del adulto, siendo 1,75 g/kg/d. Todas las dosis anteriores son dosis de fármaco crudo. Se les administró 10 veces la dosis de un adulto a las ratas del grupo vitamina C, siendo 0,05 g/kg/d. El grupo de diabéticos y el grupo de control recibieron la misma cantidad de agua destilada. El tiempo de entrega del fármaco fue de 16 semanas. El ganglio de la raíz dorsal se colocó en un tubo de congelación al final del experimento. Los cambios morfológicos de los cuerpos de Nissl en el ganglio de la raíz dorsal se detectaron mediante tinción de HE y Nissl. Los resultados del estudio mostraron que la vitamina C no tuvo un efecto significativo sobre la cantidad, el tamaño y el nucléolo. Tangzhouling puede mejorar la morfología, la cantidad y el nucléolo de los cuerpos de Nissl hasta cierto punto, y es mejor la dosis alta que la dosis baja. Las cápsulas de Tangzhouling pueden mejorar la función nerviosa de las ratas DM a través de los cuerpos de Nissl.
Subject(s)
Animals , Rats , Peripheral Nervous System Diseases , Diabetic Neuropathies , Ganglia, Spinal/drug effects , Nissl Bodies/drug effects , Staining and Labeling , Disease Models, AnimalABSTRACT
OBJECTIVE@#To evaluate the efficacy of Wen-Luo-Tong Granules (WLT) local administration in the treatment of patients with peripheral neuropathy (PN) induced by chemotherapy or target therapy.@*METHODS@#This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT (39 cases) and control groups (39 cases) using a block randomization method. The WLT group received WLT (hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (QLQ-CIPN20), and Quality of Life Questionnaire-Core30 (QLQ-C30).@*RESULTS@#After treatment, the PN grade in the WLT group was significantly lower than that in the control group (1.00 ± 0.29 vs. 1.75 ± 0.68, P<0.01). The total effective rate in the WLT group was significantly higher than that in the control group (82.05% vs. 51.28%, P<0.01). Compared with the control group, the touch-detection thresholds at fingertips, neuropathy symptom score, QLQ-CIPN 20 (sensory scale, motor scale, autonomic scale, and sum score), and QLQ-C30 (physical functioning, role functioning, emotional functioning, and global health) in the WLT group significantly improved after treatment (P<0.01 or P<0.05).@*CONCLUSION@#WLT local administration was significantly effective in the treatment of patients with PN induced by chemotherapy or target therapy. (Trial registration No. ChiCTR1900023862).
Subject(s)
Humans , Antineoplastic Agents/adverse effects , China , Japan , Peripheral Nervous System Diseases/drug therapy , Quality of Life/psychology , Surveys and QuestionnairesABSTRACT
OBJECTIVE@#To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats.@*METHODS@#Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot.@*RESULTS@#EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01).@*CONCLUSION@#EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.
Subject(s)
Animals , Male , Rats , Electroacupuncture/methods , Hyperalgesia/therapy , Microcirculation , NF-E2-Related Factor 2 , Oxaliplatin/adverse effects , Peripheral Nervous System Diseases/chemically induced , Rats, Sprague-DawleyABSTRACT
OBJECTIVE@#To construct and validate a nomogram for predicting the risk of secondary peripheral neuropathy in patients with advanced lung cancer.@*METHODS@#The sociodemographic and clinical data of 335 patients with advanced lung cancer admitted to Department of Respiratory, the First Affiliated Hospital of Zhejiang University School of Medicine from May 2020 to May 2021 were retrospectively collected. Pearson correlation analysis, univariate and multivariate logistic regression analyses were used to identify the risk factors of secondary peripheral neuropathy in patients with advanced lung cancer. A nomogram was constructed according to the contribution of each risk factor to secondary peripheral neuropathy, and the receiver operating characteristic (ROC) curve, Calibration curve and clinical decision curve were used to evaluate differentiation, calibration, and the clinical utility of the model. The nomogram was further validated with data from 64 patients with advanced lung cancer admitted between June 2021 and August 2021.@*RESULTS@#The incidences of secondary peripheral neuropathy in two series of patients were 34.93% (117/335) and 40.63% (26/64), respectively. The results showed that drinking history ( OR=3.650, 95% CI: 1.523-8.746), comorbid diabetes ( OR=3.753, 95% CI: 1.396-10.086), chemotherapy ( OR=2.887, 95% CI: 1.046-7.970), targeted therapy ( OR=8.671, 95% CI: 4.107-18.306), immunotherapy ( OR=2.603, 95% CI: 1.337-5.065) and abnormal liver and kidney function ( OR=12.409, 95% CI: 4.739-32.489) were independent risk factors for secondary peripheral neuropathy (all P<0.05). A nomogram was constructed based on the above risk factors. The area under the ROC curve (AUC) of the nomogram for predicting the secondary peripheral neuropathy was 0.913 (95% CI: 0.882-0.944); and sensitivity, specificity, positive and negative predictive values were 85.47%, 81.65%, 71.43% and 91.28%, respectively. The Calibration curve and clinical decision curve showed good calibration and clinical utility. External validation results showed that the AUC was 0.764 (95% CI: 0.638-0.869); and sensitivity, specificity, positive and negative predictive values were 79.28%, 85.79%, 73.25% and 85.82%, respectively.@*CONCLUSIONS@#Advanced lung cancer patients have a high risk of secondary peripheral neuropathy after anticancer therapy. Drinking history, comorbid diabetes, chemotherapy, targeted therapy, immunotherapy, abnormal liver and kidney function are independent risk factors. The nomogram prediction model constructed in the study is effective and may be used for the risk assessment of secondary peripheral neuropathy in patients with advanced lung cancer.
Subject(s)
Humans , Nomograms , Retrospective Studies , Peripheral Nervous System Diseases/etiology , Risk Factors , Lung Neoplasms/complicationsABSTRACT
Abstract Acrylamide is a neurotoxic compound. Moreover, anakinra is an interleukin-1 (IL-1) receptor antagonist used in rheumatoid arthritis treatment. This study investigated the effect of anakinra on acrylamide-related neuropathy and neuropathic pain. Acrylamide exposure caused a significant decrease in the pain threshold; an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) levels; and a decrease in total glutathione (tGSH) values in the sciatic nerve. This indicates hyperalgesia presence, oxidative stress, and peripheral nerve tissue inflammation. Anakinra treatment significantly reduced the MDA, IL-1ß, and TNF-α levels, and increased the pain threshold and mean tGSH values. The analgesic effect of anakinra was 67.9% at the first hour, increasing to 74.9% and 76.7% at the second and third hours, respectively. The group receiving acrylamide exhibited histopathological changes (e.g., swollen and degenerated axons, hypertrophic and hyperplasic Schwann cells, and congested vessels). The use of anakinra significantly improved these morphological changes. Anakinra is concluded to reduce neuropathic pain and prevent neurotoxic effect of acrylamide on peripheral nerves due to its analgesic, antioxidant, and anti-inflammatory properties
Subject(s)
Animals , Male , Rats , Peripheral Nervous System Diseases/pathology , Acrylamide/adverse effects , Interleukin 1 Receptor Antagonist Protein/antagonists & inhibitors , Inflammation/classification , Peripheral Nerves/abnormalities , Arthritis, Rheumatoid/pathology , Tumor Necrosis Factor-alpha/pharmacology , Pain Threshold/classification , Oxidative Stress/drug effectsABSTRACT
SUMMARY: Peripheral nerve damage (PNI) can cause demyelination, axonal degeneration and loss of motor and sensory function. Melatonin with its antioxidative effect, has been reported to reduce scar formation in nerve injury, take a role in repair process by suppressing fibroblast proliferation in the damaged area. It was aimed to investigate the effect of melatonin in the repair of peripheral nerve damage and the relationship between S100 proteins and angiogenic regulation. Wistar albino rats were divided into 3 groups. In the Defect group, 6 mm tibial bone defect using a motorized drill was created and kept immobile for 28 days. In Defect + graft group, tibial bone defect with allograft treatment was applied and kept immobile for 28 days. In Defect + graft + Melatonin group, melatonin was administered to defect + allograft group. All rats were sacrified by decapitation, skin and tibia bone were removed then fixed with 10 % neutral buffered formalin and embedded in paraffin, sections were examined under light microscopy. In the Defect+Graft group, enlargement and occlusion of the vessels with degeneration of the epineural sheath, thickening of the endoneural sheath and mild hyperplasia of schwannocytus (Schwann cells) were remarkable. In the Defect+Graft+Melatonin group, the epineural sheath was tight and regular, the axonal structures were prominent in the endoneural area. Mild S100 expression was observed in Defect+Graft group in fibers of the endoneural region with a prominent expression in schwannocytus. In Defect+Graft+Melatonin group (10mg/kg), S100 expression was moderate in areas where schwannocytus proliferated and nerve-connective tissue sheaths were reconstructed. VEGF expression was moderate in endoneural, perineural and epineural connective tissue sheaths in the Defect+Graft+Melatonin group, with negative expression in blood vessel endothelial cells, but with a positive expression in schwannocytus. We conclude that with the application of melatonin; oxidative stress decreases, schwannocytus proliferation increases, having positive influence on nerve repair with the regulation of S100 signaling and angiogenetic structuring.
RESUMEN: El daño a los nervios periféricos puede causar desmielinización, degeneración axonal y pérdida de la función motora y sensorial. Se ha informado que la melatonina, con su efecto antioxidante, reduce la formación de cicatrices en lesiones nerviosas y desempeña un papel en el proceso de reparación al suprimir la proliferación de fibroblastos en el área dañada. El objetivo de este trabajo fue investigar el efecto de la melatonina en la reparación del daño de los nervios periféricos y la relación entre las proteínas S100 y la regulación angiogénica. Ratas albinas Wistar se dividieron en 3 grupos. En el grupo Defecto, se creó un defecto óseo tibial de 6 mm con un taladro motorizado y se mantuvo inmóvil durante 28 días. En el grupo Defecto + injerto, se aplicó tratamiento de defecto óseo tibial con aloinjerto y se mantuvo inmóvil durante 28 días. En el grupo Defecto + injerto + Melatonina, se administró melatonina al grupo defecto + aloinjerto. Todas las ratas fueron sacrificadas por decapitación, se extrajo la piel y el hueso de la tibia y luego se fijaron con formalina tamponada neutra al 10 % y se incluyeron en parafina, las secciones se examinaron bajo microscopía óptica. En el grupo Defecto+Injerto, fueron notables el agrandamiento y la oclusión de los vasos con degeneración de la vaina epineural, engrosamiento de la vaina endoneural e hiperplasia leve de los schwannocitos (neurolemnocitos). En el grupo Defecto+Injerto+Melatonina, la vaina epineural era estrecha y regular, las estructuras axonales eran prominentes en el área endoneural. Se observó expresión leve de S100 en el grupo Defecto+Injerto en fibras de la región endoneural con una expresión prominente en los schwannocitos. En el grupo Defecto+Injerto+Melatonina, la expresión de S100 fue moderada en áreas donde proliferaron los schwannocitos y se reconstruyeron las vainas de tejido conectivo nervioso. La expresión de VEGF fue moderada en vainas de tejido conectivo endoneural, perineural y epineural en el grupo Defecto+Injerto+Melatonina, con expresión negativa en células endoteliales de vasos sanguíneos, pero con expresión positiva en schwannocitos. Concluimos que con la aplicación de melatonina; disminuye el estrés oxidativo, aumenta la proliferación de schwannocitos, influyendo positivamente en la reparación nerviosa con la regulación de la señalización S100 y la estructuración angiogenética.
Subject(s)
Animals , Rats , Tibia/pathology , Peripheral Nervous System Diseases/drug therapy , Melatonin/administration & dosage , Antioxidants/administration & dosage , Peripheral Nerves/drug effects , Tibia/innervation , S100 Proteins , Rats, Wistar , Vascular Endothelial Growth Factor A , Disease Models, Animal , FibroblastsABSTRACT
ABSTRACT Background: This mini-review aims to summarize and discuss previous and recent advances in the clinical presentation, pathophysiology, diagnosis, treatment, and outcome of SARS-CoV-2-associated peripheral neuropathies. Methods: Literature review. Results: Altogether, 105 articles about SARS-CoV-2-associated neuropathy describing 261 patients were retrieved. Peripheral neuropathy in patients with COVID-19 is frequent and predominantly due to immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, due to the compression of peripheral nerves resulting from prolonged bedding in the Intensive Care Unit (ICU) and pre-existing risk factors such as diabetes. SARS-CoV-2 does not cause viral neuropathy. Neurotoxic drugs such as daptomycin, linezolid, lopinavir, ritonavir, hydro-chloroquine, cisatracurium, clindamycin, and glucocorticoids should be administered with caution and patients should be appropriately bedded in the ICU to prevent SARS-CoV-2-associated neuropathy. Patients with Guillain-Barré syndrome (GBS) benefit from immunoglobulins, plasma exchange, and steroids. Conclusions: Neuropathies of peripheral nerves in patients with COVID-19 are frequent and mostly result from immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, from the compression of peripheral nerves due to prolonged bedding on the ICU. SARS-CoV-2 does not cause infectious neuropathy.
RESUMO Introdução: A presente minirrevisão tem como objetivo resumir e discutir os avanços dos aspectos clínicos, fisiopatológicos, de diagnóstico, tratamento e evolução das neuropatias dos nervos periféricos associadas à COVID-19. Métodos: Revisão da literatura. Resultados: Foram avaliados 105 artigos sobre neuropatia associada à COVID-19. Nesses estudos, 261 pacientes apresentaram boa evolução. As neuropatias dos nervos periféricos em pacientes com COVID-19 são frequentes e se devem, principalmente, aos mecanismos immunológicos ou efeitos colaterais neurotóxicos dos medicamentos utilizados para o tratamento da COVID-19, a fatores de risco pré-existentes, como diabetes e, em menor parte, à compressão dos nervos periféricos nos leitos da UTI. A COVID-19 não causa neuropatia viral. Os medicamentos neurotóxicos, como daptomicina, linezolida, lopinavir, ritonavir, hidro-cloroquina, cisatracúrio, clindamicina e glicocorticoides devem ser administrados com cautela, e os pacientes deve ser adequadamente admitidos nos leitos da UTI para prevenir o desenvolvimento de neuropatia associada à COVID-19. Pacientes com síndrome de Guillain-Barré (GBS) se beneficiam de imunoglobulinas, plasmaférese e esteroides. Conclusões: As neuropatias dos nervos periféricos em pacientes com COVID-19 são raras e predominantemente devidas aos efeitos colaterais neurotóxicos das mecanismos immunológicos ou drogas utilizadas para o tratamento de COVID-19 e, em menor parte, devido à compressão dos nervos periféricos nos leitos da UTI. A COVID-19 não causa neuropatia infeciosa.
Subject(s)
Humans , Pharmaceutical Preparations , Peripheral Nervous System Diseases/chemically induced , Guillain-Barre Syndrome/chemically induced , COVID-19 , Antiviral Agents , Bedding and Linens , Risk Factors , SARS-CoV-2 , Intensive Care UnitsABSTRACT
Objective To outline the epidemiological profile of surgical patients treated at the peripheral-nerve outpatient clinic of a public hospital in the state of Pernambuco, Brazil, from 2008 (the year this service was implemented in the hospital ) to 2016. Material and Methods A cross-sectional study with data collection from the medical records. A descriptive analysis was performed with the qualitative variables presented as relative and absolute frequencies, and the quantitative variables, as means and standard deviations. The studied variables were gender, age, diagnosis, and surgical techniques. Results In total, 506 medical records were analyzed. Of these, 269 were of male patients (53%), and 238 were of female patients (46%). The age of the sample ranged from 5 to 84 years (41 14 years). The most prevalent diagnoses were: carpal tunnel syndrome (38.9%) followed by traumatic brachial plexus injury (33.2%). The first diagnosis was more frequent among women, while the second, among men. This collaborates with the predominant findings of upper-limb lesions (91%), in which men accounted for 52,75% (244) and women, for 47,25% (217). Conclusion The present study provided relevant information regarding the reality of peripheral-nerve surgeries performed at a public hospital in the state of Pernambuco, Brazil. Public health issues increasingly require the continuity of public policies and government incentive.
Subject(s)
Carpal Tunnel Syndrome/epidemiology , Ulnar Nerve Compression Syndromes/epidemiology , Peripheral Nervous System Diseases/surgery , Peripheral Nervous System Diseases/epidemiology , Brachial Plexus Neuropathies/epidemiology , Socioeconomic Factors , Surgical Procedures, Operative , Brazil/epidemiology , Medical Records , Epidemiology, Descriptive , Cross-Sectional Studies , Retrospective Studies , Data Interpretation, Statistical , Statistics, NonparametricABSTRACT
INTRODUCCIÓN: La endometriosis afecta hasta un 10-15% de las mujeres jóvenes. Se define como tejido endometrial funcional fuera de la cavidad uterina y su presentación clásica es la dismenorrea. La variedad profunda afecta a un 1-2% y las localizaciones más frecuentes son el peritoneo pélvico, ovarios, ligamentos útero-sacros y septum recto-vaginal; sin embargo, puede presentarse de forma muy infrecuente como implantes aislados localizados en relación al nervio ciático. El diagnóstico habitualmente es complejo y tardío, dado que los síntomas son inespecíficos y el examen físico puede ser indistinguible de otras etiologías. El estudio imagenológico de elección para la endometriosis profunda es la resonancia magnética (RM) de pelvis ya que una adecuada localización pre-quirúrgica de las lesiones es fundamental. CASO CLÍNICO: Paciente de sexo femenino de 46 años, con tres años de dolor pélvico, dismenorrea y dispareunia. El síntoma cardinal fue dolor ciático progresivo, con déficit motor y alteraciones sensitivas, los cuales se exacerbaban durante la menstruación y no presentaban respuesta al tratamiento farmacológico. En la RM se identifica nódulo sólido sospechoso de endometriosis en relación al nervio ciático derecho. El caso es evaluado por un comité multidisciplinario y se realiza cirugía laparoscópica. El diagnóstico de sospecha es confirmado histológicamente. La paciente presenta buena recuperación post-quirúrgica y cese completo de los síntomas descritos. DISCUSIÓN: La endometriosis profunda presenta un reto diagnóstico y habitualmente es tardío. Este caso presenta el resultado exitoso de una buena sospecha clínica, un estudio imagenológico completo y la resolución con una técnica quirúrgica compleja.
INTRODUCTION: Endometriosis is a disease that affects 10-15% of young women. It is characterized as functional endometrial tissue outside the uterine cavity. The most common form of presentation is dysmenorrhea. Deep endometriosis affects 1-2% of the patients, and is frequently located in the pelvic peritoneum, ovaries, utero-sacral ligaments and recto-vaginal septum. The isolated endometriosis of the sciatic nerve is a very uncommon presentation of this disease. Late diagnosis is frequent, mainly because the symptoms are non-specific, and the physical examination may be indistinguishable from other etiologies. The imaging study of choice is the pelvic magnetic resonance imaging (MRI) and an accurate pre-surgical location of the lesions is critical for a successful surgical outcome. CLINICAL CASE: 46-year-old female patient with 3 years of pelvic pain, dysmenorrhea and dyspareunia. The cardinal symptom was progressive sciatic pain, with motor deficit and sensory alterations. The pain was persistent despite pharmacological treatment and exacerbated during menstruation. MRI identifies a nodule located in the pelvic portion of the right sciatic nerve, suggestive of an endometriosis implant. The case was discussed by a multidisciplinary committee and laparoscopic surgery was performed. The diagnosis was confirmed with histology. The patient recovered well from surgery with significant improvement of the previously described symptoms. DISCUSSION: The diagnosis of deep endometriosis is challenging and usually delayed. This rare disease had a successful outcome, due to an early clinical suspicion, a thorough imaging study and an effective resolution with a complex surgical technique.
Subject(s)
Humans , Female , Middle Aged , Sciatic Nerve/surgery , Sciatic Nerve/diagnostic imaging , Peripheral Nervous System Diseases/surgery , Peripheral Nervous System Diseases/diagnostic imaging , Endometriosis/surgery , Endometriosis/diagnostic imaging , Magnetic Resonance Imaging , Laparoscopy , Pelvic Pain/etiologyABSTRACT
OBJECTIVE@#Distal hereditary motor neuropathy (dHMN) comprises a heterogeneous group of inherited disorders associated with neurodegeneration of motor nerves and neurons, mainly charac-terized by progressive atrophy and weakness of distal muscle without clinical or electrophysiological sensory abnormalities. To improve the recognition and diagnosis of the disease, we summarized the clinical manifestations, electrophysiological, pathological, and genetic characteristics in eight patients with dHMN.@*METHODS@#Eight probands from different families diagnosed with dHMN were recruited in this study between June 2018 and April 2019 at Peking University People's Hospital. Eight patients underwent complete neurological examination and standard electrophysiological examinations. The clinical criteria were consistent with the patients presenting with a pure motor neuropathy with no sensory changes on electrophysiology. The detailed clinical symptoms, neurophysiological examinations, pathological features and gene mutations were analyzed retrospectively. Genetic testing was performed on the eight patients using targeted next-generation sequencing panel for inherited neuromuscular disorder and was combined with segregation analysis.@*RESULTS@#The age of onset ranged between 11 and 64 years (median 39.5 years) in our dHMN patients. All the cases showed a slowly progressive disease course, mainly characterized by distal limb muscle weakness and atrophy. The motor nerve conduction revealed decreased compound muscle action potential amplitude and velocity, while the sensory nerve conduction velocities and action potentials were not affected. Needle electromyography indicated neurogenic chronic denervation in all patients. Muscle biopsy performed in two patients demonstrated neurogenic skeletal muscle damage. Sural nerve biopsy was performed in one patient, Semithin sections shows relatively normal density and structure of large myelinated fibers, except very few fibers with thin myelin sheaths, which suggested very mild sensory nerve involvement. Eight different genes known to be associated with dHMN were identified in the patients by next-generation sequencing, pathogenic dHMN mutations were identified in three genes, and the detection rate of confirmed genetic diagnosis of dHMN was 37.5% (3/8). Whereas five variants of uncertain significance (VUS) were identified, among which two novel variants co-segregated the phenotype.@*CONCLUSION@#dHMN is a group of inherited peripheral neuropathies with great clinical and genetic heterogeneity. Next-generation sequencing is widely used to discover pathogenic genes in patients with dHMN, but more than half of the patients still remain genetically unknown.
Subject(s)
Adolescent , Adult , Child , Humans , Middle Aged , Young Adult , Hereditary Sensory and Motor Neuropathy/genetics , Mutation , Peripheral Nervous System Diseases , Phenotype , Retrospective StudiesABSTRACT
RESUMO: A atrofia óptica autossômica dominante (ADOA) é uma das formas mais comuns de atrofias ópticas hereditárias, e causada por mutações no gene OPA1. Os pacientes afetados por essa doença geralmente apresentam perda visual na primeira década de vida, podendo apresentar manifestações extraoftalmológicas no decorrer dos anos, configurando uma síndrome chamada OPA1 plus ou ADOA-plus. Objetivos: Relatar caso de paciente portadora da síndrome ADOA-plus, estabelecendo correlações com casos descritos na literatura. Relato de caso: Paciente feminino, 30 anos, foi encaminhada para avaliação de quadro de atrofia óptica progressiva associada a sintomas de neuropatia periférica. Aos dois anos, foi diagnosticada com perda visual parcial em consulta de puericultura. Não relatou outros sintomas associados durante a infância e a adolescência. Aos 20 anos, apresentou dificuldades de deambular, fraqueza em membros inferiores e falta de equilíbrio. Aos 25 anos, após extensa investigação, foi identificada, através de sequenciamento de exoma, mutação patológica no gene OPA1 confirmando o diagnóstico ADOA-plus e iniciado tratamento com Coenzima Q10. Atualmente a paciente relata ataxia sensitiva, diminuição da acuidade visual progressiva, fasciculações e câimbras em MMII, disfagia e dispneia. Discussão: Muitos pacientes com ADOA-plus apresentam surdez neurossensorial como sintoma extraoftalmológico mais comum, além de quadros de parkinsonismo e demência, ataxia e ptose. Paciente relatada constitui um caso de atrofia óptica associado à neuropatia periférica, ataxia e miopatia. Devido à ampla variabilidade clínica dessa doença, deve-se investigar mutações no OPA1 em casos de paraparesia espástica progressiva associada à atrofia óptica, visto que possibilidade de tratamento com Coenzima Q10. (AU)
ABSTRACT: Introduction: Autosomal dominant optic atrophy (ADOA) is one of the most common forms of inherited optic atrophies and is caused by mutations in the OPA1 gene. Patients affected by this disease usually present visual loss in the first decade of life, and may present extra-ophthalmologic manifestations over the years, configuring a syndrome called OPA1 plus or ADOA-plus. Objectives: to report the case of a patient with ADOA-plus syndrome, establishing correlations with cases described in the literature, Case report: a 30-year-old female patient was referred for evaluation of progressive optic atrophy associated with symptoms of peripheral neuropathy. At two years of age, she was diagnosed with partial visual loss during a childcare visit. She reported no other associated symptoms during childhood and adolescence. At the age of 20, she presented with difficulty walking, lower limb weakness, and poor balance. At 25, after extensive investigation, a pathological mutation in the OPA1 gene was identified through exome sequencing, confirming the diagnosis of ADOA-plus, and treatment with Coenzyme Q10 was initiated. Currently the patient reports sensory ataxia, progressive decrease in visual acuity, fasciculations and cramps in the lower limbs, dysphagia and dyspnea. Discussion: Many patients with ADOA-plus present sensorineural deafness as the most common extra-ophthalmologic symptom, in addition to parkinsonism and dementia, ataxia and ptosis. The patient reported is a case of optic atrophy associated with peripheral neuropathy, ataxia and myopathy. Due to the wide clinical variability of this disease, OPA1 mutations should be investigated in cases of progressive spastic paraparesis associated with optic atrophy, since the possibility of treatment with Coenzyme Q10. (AU)