RESUMEN
OBJECTIVE: To identify the prevalence and clinical features of leflunomide-associated peripheral neuropathy in patients with rheumatic disease over a 42-month observational period between January 1, 2016 and June 30, 2019. METHODS: A retrospective observational study was conducted using regional prescription data identifying all patients treated with leflunomide for rheumatic diseases in the Southern District Health Board of New Zealand. Medical records were used to identify patients who developed peripheral neuropathy while receiving treatment with leflunomide. Demographic characteristics, co-therapies, and additional risk factors for peripheral neuropathy were also recorded. RESULTS: A total of 482 patients were identified as receiving leflunomide for the treatment of rheumatic during the study period. In total, 23 patients developed leflunomide-induced peripheral neuropathy within the cohort giving a prevalence of 4.7%. Nerve conduction studies (NCS) performed in 18 (78.2%) of these patients confirmed a distal axonal, sensory, or sensorimotor peripheral neuropathy. The majority of patients (n = 22; 95.6%) either improved, stabilized, or resolved on cessation of the drug, with or without medication washout. Adverse symptoms were reported in association with peripheral neuropathy in 15 of the 23 patients (65.2%): these included pain, poor sleep, compromised skin integrity, poor balance, and a Charcot-like arthropathy. Additional treatment was required to manage symptoms of peripheral neuropathy including nine patients (39%) who received pain relief. CONCLUSIONS: This study supports the previously reported association between leflunomide treatment and the development of a peripheral neuropathy. However, our findings suggest that this is more common than the previous estimates. In patients with psoriatic arthritis and previous tarsitis, there appeared to be an association with a Charcot's-like arthropathy, a complication not previously noted in the literature.
Asunto(s)
Antirreumáticos , Leflunamida , Enfermedades del Sistema Nervioso Periférico , Enfermedades Reumáticas , Humanos , Leflunamida/efectos adversos , Masculino , Femenino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Prevalencia , Nueva Zelanda/epidemiología , Anciano , Adulto , Antirreumáticos/efectos adversos , Factores de Riesgo , Factores de Tiempo , Conducción Nerviosa/efectos de los fármacosAsunto(s)
Antibacterianos , Humanos , Antibacterianos/efectos adversos , Fluoroquinolonas/efectos adversos , Polineuropatías/inducido químicamente , Masculino , Enfermedades Desmielinizantes/inducido químicamente , Femenino , Persona de Mediana Edad , Anciano , Conducción Nerviosa/efectos de los fármacosRESUMEN
Background and purpose:
The aim of this study is to comprehensively determine the types of affected fibers in Parkinson’s disease (PD) patients by employing nerve conduction studies (NCS), sympathetic skin response (SSR) examinations, and current perception threshold (CPT) testing and to analyze the correlation between levodopa use and nerve involvement.
. Methods:This retrospective study included 36 clinically diagnosed PD patients who were recruited between January 2018 and April 2019. All patients underwent NCS, SSR testing, and CPT sensory examinations. Additionally, the PD patients were assessed for disease staging using the Hoehn and Yahr (H-Y) scale.
. Results:Fifteen patients were included in the tremor-dominant subtype, ten patients in the rigid-dominant subtype, and eleven patients in the mixed subtype. Eleven patients were using levodopa, while twenty-five patients had never used any anti-Parkinson’s medication. Ten patients (28%) showed abnormal sympathetic skin responses (SSR). The CPT examination revealed sensory abnormalities in twenty-four patients (67%), with eighteen patients (75%) experiencing sensory hypersensitivity and six patients (25%) experiencing sensory hypoesthesia. Twelve patients (33%) had normal CPT results. Among the patients with abnormal CPT findings, seven cases (29%) involved large myelinated fiber damage, twenty-two cases (92%) involved small myelinated fiber damage, and nineteen cases (79%) involved unmyelinated fiber damage. The rate of sensory abnormalities was 64% (7/11) in the levodopa group and 68% (17/25) in the non-levodopa group, with no statistically significant difference between the two groups.
. Conclusion:The incidence of abnormal CPT findings in PD patients was higher than that of abnormal SSR responses, suggesting that nerve fiber damage primarily affects small fiber nerves (SFN).
.Asunto(s)
Levodopa , Conducción Nerviosa , Enfermedad de Parkinson , Humanos , Levodopa/administración & dosificación , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/complicaciones , Persona de Mediana Edad , Femenino , Anciano , Estudios Retrospectivos , Masculino , Conducción Nerviosa/efectos de los fármacos , Fibras Nerviosas/patología , Fibras Nerviosas/efectos de los fármacos , Antiparkinsonianos/uso terapéutico , Antiparkinsonianos/efectos adversos , Nervios Periféricos/patologíaRESUMEN
Injury of a peripheral nerve (PNI) leads to both ischemic and inflammatory alterations. Sciatic nerve injury (SNI) represents the most widely used model for PNI. Mesenchymal stem cell-based therapy (MSCs) has convenient properties on PNI by stimulating the nerve regeneration. Melatonin has cytoprotective activity. The neuroprotective characteristics of MSCs and melatonin separately or in combination remain a knowledge need. In the rats-challenged SNI, therapeutic roles of intralesional MSCs and intraperitoneal melatonin injections were evaluated by functional assessment of peripheral nerve regeneration by walking track analysis involving sciatic function index (SFI) and two electrophysiological tests, electromyography and nerve conduction velocity, as well as measurement of antioxidant markers in serum, total antioxidant capacity (TAC) and malondialdehyde, and mRNA expression of brain derived neurotrophic factor (BDNF) in nerve tissues in addition to the histopathological evaluation of nerve tissue. Both individual and combination therapy with MSCs and melatonin therapies could effectively ameliorate this SNI and promote its regeneration as evidenced by improving the SFI and two electrophysiological tests and remarkable elevation of TAC with decline in lipid peroxidation and upregulation of BDNF levels. All of these led to functional improvement of the damaged nerve tissues and good recovery of the histopathological sections of sciatic nerve tissues suggesting multifactorial synergistic approach of the concurrent usage of melatonin and MSCs in PNI. The combination regimen has the most synergistic neuro-beneficial effects in PNI that should be used as therapeutic option in patients with PNI to boost their quality of life.
Asunto(s)
Antioxidantes , Melatonina , Trasplante de Células Madre Mesenquimatosas , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Nervio Ciático , Animales , Melatonina/farmacología , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Ratas , Nervio Ciático/efectos de los fármacos , Nervio Ciático/lesiones , Regeneración Nerviosa/efectos de los fármacos , Masculino , Antioxidantes/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Modelos Animales de Enfermedad , Ratas Wistar , Conducción Nerviosa/efectos de los fármacos , Ratas Sprague-DawleyRESUMEN
BACKGROUND: To evaluate the efficacy of rituximab in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients not responding to conventional immune therapies. METHODS: An open-label, prospective exploratory study was conducted with intravenous rituximab on 17 CIDP patients who had not responded to at least two first-line therapies. The primary endpoint was to determine the proportion of patients who showed improvement 6 months after rituximab therapy. The percentage of responders to rituximab, along with a 95% CI, was reported and compared with the 30% response rate after other immunosuppressive drugs previously documented in the literature. RESULTS: 13 of the 17 treated patients (76.5%) showed improvement at 6 months (95% CI 50.1 to 93.2). Among the 14 patients who completed the 12-month follow-up (2 were lost to follow-up after showing improvement at months 8 and 10, and 1 deteriorated at 6 months), 13 (92.9%) demonstrated improvement at 12 months (95% CI 66.1 to 99.8). Nerve conduction parameters improved by at least 20% in two nerves in 6 out of 15 (40%) patients at 6 months and in 7 out of 13 (53.9%) at 12 months. None of the treated patients withdrew from the study due to side effects. There was a significant reduction of circulating CD19+ cells 15 days, 2, 6 and 12 months after treatment. CONCLUSION: Rituximab seems to be a safe therapy in most patients with CIDP not responding to conventional immune therapies. The high percentage of patients who improved in this study suggests a possible positive effect of rituximab which is worth investigating in future randomised controlled clinical trials. TRIAL REGISTRATION NUMBER: NCT05877040.
Asunto(s)
Factores Inmunológicos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Rituximab , Humanos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Rituximab/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Anciano , Factores Inmunológicos/uso terapéutico , Resultado del Tratamiento , Conducción Nerviosa/efectos de los fármacosRESUMEN
BACKGROUND AND AIM: Recreational use of nitrous oxide (N2O) has been associated with the development of severe nitrous oxide-induced neuropathy (N2On). Follow-up of these patients poses challenges, and their clinical progression remains largely unknown. The identification of prognostic factors is made difficult by the lack of standardized longitudinal assessments in most studies. The objective was to document the course of neuropathy through systematic follow-up assessments in N2On patients to identify prognostic factors for persistent disability after 6 months. METHODS: We gathered demographic, clinical, biological, and electrophysiological data from N2On patients hospitalized in the Referral center in Marseille, both at baseline and during a standardized follow-up assessment at 6 months. RESULTS: We retrospectively included 26 N2On patients (mean age 22.6 ± 4.4). Significant improvements were observed in all main clinical scores including Rankin, ONLS, and MRC testing (p < .01). Electrophysiological studies (EDX) revealed a predominantly motor neuropathy with marked reduction in CMAP in the lower limbs at baseline, and no significant improvement in motor parameters (p = .543). Rankin score at 6 months correlated with the initial weekly N2O consumption (r = .43, p = .03) and the CMAP sum score in the lower limbs at the first EDX (r = -.47, p = .02). Patients with and without myelitis showed similar Rankin and ONLS score after 6 months. INTERPRETATION: The clinical course generally improved favorably at 6 months with notable amelioration in the primary disability scores, sensory deficits, and ataxia. However, distal motor impairment associated with peripheral neuropathy persisted, with distal axonal loss emerging as the main prognostic factor for long-term disability in these young patients.
Asunto(s)
Óxido Nitroso , Enfermedades del Sistema Nervioso Periférico , Humanos , Óxido Nitroso/efectos adversos , Óxido Nitroso/administración & dosificación , Masculino , Femenino , Adulto , Adulto Joven , Estudios Retrospectivos , Pronóstico , Estudios Longitudinales , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Estudios de Seguimiento , Adolescente , Conducción Nerviosa/fisiología , Conducción Nerviosa/efectos de los fármacosRESUMEN
INTRODUCTION/AIMS: Electrodiagnostic examinations, such as nerve conduction studies (NCS) and needle electromyography (EMG), are perceived as painful by children and their parents/guardians. Methods to reduce peri-procedural pain improve compliance and have neurocognitive and neuropsychiatric benefits. This study aimed to assess the efficacy of combined oral and topical analgesics (COTA), oral analgesics (OA), and placebo in reducing pain during NCS/EMG in children. METHODS: We performed a double-blind, randomized, placebo-controlled trial on children presenting to our neurophysiology lab. Patients were stratified into two age groups (6M-6Y and 7Y-18Y) and randomized into three arms: COTA, OA, and placebo. Pain scores post-NCS/EMG were assessed using the Modified Behavioral Pain Scale (MBPS) and Faces Pain Scale-Revised (FPS-R). RESULTS: One hundred thirteen participants were enrolled. A comparison of participants from both age groups combined revealed no significant differences in guardian FPS-R scores across all arms for NCS and EMG. A significant difference in the distribution of post-NCS FPS-R score severities in children aged 7Y-18Y was noted between OA and placebo (p = .007). EMG was more painful than NCS across all arms (p < .05). In children aged 6M-6Y undergoing at least 10 muscle samplings during EMG, those receiving COTA had significantly lower pain scores (p = .014). DISCUSSION: This study reveals the complexity of pediatric pain perception during NCS/EMG and highlights that other methods to reduce experienced pain are required. Our findings suggest that procedural characteristics, such as number of muscles sampled, may influence the effectiveness of analgesia and serve as a foundation for future research aimed at optimizing pain management strategies.
Asunto(s)
Administración Tópica , Electromiografía , Dimensión del Dolor , Humanos , Niño , Masculino , Femenino , Adolescente , Método Doble Ciego , Administración Oral , Preescolar , Dimensión del Dolor/métodos , Analgésicos/administración & dosificación , Analgesia/métodos , Electrodiagnóstico/métodos , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , Dolor/tratamiento farmacológico , Dolor/diagnósticoRESUMEN
BACKGROUND: Intravenous immunoglobulin (IVIg) and plasmapheresis (PLEX) are recommended in moderate to severe Guillain-Barré Syndrome (GBS), but there is paucity of studies evaluating its effect on nerve conduction studies (NCS). We report the effect of IVIg and PLEX on the NCS parameters and clinical outcomes compared to natural course (NC) of GBS patients. METHOD: Moderate to severe GBS patients were included based on clinical, cerebrospinal fluid, and NCS finding. Six motor and sensory nerves were evaluated at admission, one month and 3 months, and NCS subtyping was done. Axonal and demyelination burden in motor nerves and early reversible conduction block (ERCB) were noted. Patients receiving IVIg, PLEX or on NC were noted. Outcome was defined at 3 months into complete, partial and poor using a 0-6 GBS Disability Scale (GBSDS). RESULT: Seventy-two patients were included, whose median age was 36 years and 22(30.6 %) were females. 44 patients received IVIg, 9 PLEX and 19 were in NC, and they had comparable peak disability. AIDP was the dominant subtype at admission (58.3 %), which remained so at 3 months (50 %). The shift of subtypes was the highest from the equivocal group followed by AMAN and the least from AIDP. IVIg and PLEX group had more reduction in axonal burden and had ERCB compared to NC. 33(44 %) patients had complete recovery, and 40(55.5 %) patients had concordance in clinical and neurophysiological outcome. CONCLUSION: Transition of GBS subtype may occur at follow-up from all the subtypes, the highest from the equivocal and the lowest from the AIDP group. IVIg/PLEX treatment may help in reducing conduction block and axonal burden.
Asunto(s)
Síndrome de Guillain-Barré , Inmunoglobulinas Intravenosas , Conducción Nerviosa , Plasmaféresis , Humanos , Síndrome de Guillain-Barré/terapia , Síndrome de Guillain-Barré/fisiopatología , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunoglobulinas Intravenosas/administración & dosificación , Femenino , Masculino , Adulto , Plasmaféresis/métodos , Conducción Nerviosa/fisiología , Conducción Nerviosa/efectos de los fármacos , Persona de Mediana Edad , Adulto Joven , Resultado del Tratamiento , Factores Inmunológicos/uso terapéutico , Factores Inmunológicos/administración & dosificación , AdolescenteRESUMEN
BACKGROUND: To evaluate whether ongoing axonal loss can be prevented in multifocal motor neuropathy (MMN) treated with immunoglobulin G (IgG), a group of patients with a median disease duration of 15.7 years (range: 8.3-37.8), treated with titrated dosages of immunoglobulins, was studied electrophysiologically at time of diagnosis and at follow-up. RESULTS: At follow-up, the Z-score of the compound motor action potential amplitude of the median, fibular, and tibial nerves and the neurological performances were determined. In seven patients with a treatment-free period of 0.3 years (0.2-0.4), there was no progression of axonal loss (p = 0.2), whereas a trend toward further axonal loss by 1.3 Z-scores (0.9-17.0, p = 0.06) was observed in five patients with a treatment-free period of 4.0 years (0.9-9.0). The axonal loss in the group with a short treatment delay was significantly smaller than in the group with a longer treatment delay (p = 0.02). Also, there was an association between treatment delay and ongoing axonal loss (p = 0.004). The electrophysiological findings at follow-up were associated with the isokinetic strength performance, the neurological impairment score, and the disability, supporting the clinical relevance of the electrophysiological estimate of axonal loss. CONCLUSION: Swift initiation of an immediately titrated IgG dosage can prevent further axonal loss and disability in continuously treated MMN patients.
Asunto(s)
Axones , Polineuropatías , Humanos , Masculino , Femenino , Persona de Mediana Edad , Axones/patología , Axones/efectos de los fármacos , Adulto , Anciano , Polineuropatías/tratamiento farmacológico , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Inmunoglobulina G/administración & dosificación , Enfermedad de la Neurona Motora/tratamiento farmacológico , Estudios de Seguimiento , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunoglobulinas Intravenosas/uso terapéuticoRESUMEN
BACKGROUND: The factors underlying the topography of nitrous oxide (N2O)-induced neurological complications are unknown. METHODS: We included all consecutive patients admitted to the university hospital of Marseille for N2O-induced neurological complications in a prospective observational study. Patients underwent neurological examination, spinal cord magnetic resonance imaging, and nerve conduction studies within the first 4 weeks after admission. RESULTS: In total, 61 patients were included: 45% with myeloneuropathy, 34% with isolated myelopathy, and 21% with isolated neuropathy. On multivariable analysis, the odds of myelopathy were associated with the amount of weekly N2O consumption (~600 g cylinder per week, odds ratio [OR] = 1.11, 95% confidence interval [CI] = 1.001-1.24). The extent of the myelopathy (number of vertebral segments) was correlated with the number of ~600-g cylinders consumed weekly (ρ = 0.40, p < 0.005). The odds of neuropathy were associated with the duration of consumption (per month; OR = 1.29, 95% CI = 1.05-1.58). Mean lower-limb motor nerve amplitude was correlated with the duration of consumption (in months; ρ = -0.34, p < 0.05). CONCLUSIONS: The odds of myelopathy increased with the amount of N2O consumption, and the odds of neuropathy increased with the duration of N2O exposure, which suggests distinct pathophysiological mechanisms underlying these two neurological complications.
Asunto(s)
Óxido Nitroso , Enfermedades de la Médula Espinal , Humanos , Óxido Nitroso/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Enfermedades de la Médula Espinal/inducido químicamente , Enfermedades de la Médula Espinal/diagnóstico por imagen , Estudios Prospectivos , Imagen por Resonancia Magnética , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , Adulto , Enfermedades del Sistema Nervioso Periférico/inducido químicamenteRESUMEN
BACKGROUND: Inhibition of HDAC6 has been proposed as a broadly applicable therapeutic strategy for Charcot-Marie-Tooth disease (CMT). Inhibition of HDAC6 increases the acetylation of proteins important in axonal trafficking, such as α-tubulin and Miro, and has been shown to be efficacious in several preclinical studies using mouse models of CMT. AIMS: Here, we sought to expand on previous preclinical studies by testing the effect of genetic deletion of Hdac6 on mice carrying a humanized knockin allele of Gars1, a model of CMT-type 2D. METHODS: Gars1ΔETAQ mice were bred to an Hdac6 knockout strain, and the resulting offspring were evaluated for clinically relevant outcomes. RESULTS: The genetic deletion of Hdac6 increased α-tubulin acetylation in the sciatic nerves of both wild-type and Gars1ΔETAQ mice. However, when tested at 5 weeks of age, the Gars1ΔETAQ mice lacking Hdac6 showed no changes in body weight, muscle atrophy, grip strength or endurance, sciatic motor nerve conduction velocity, compound muscle action potential amplitude, or peripheral nerve histopathology compared to Gars1ΔETAQ mice with intact Hdac6. INTERPRETATION: Our results differ from those of two previous studies that demonstrated the benefit of the HDAC6 inhibitor tubastatin A in mouse models of CMT2D. While we cannot fully explain the different outcomes, our results offer a counterexample to the benefit of inhibiting HDAC6 in CMT2D, suggesting additional research is necessary.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth , Modelos Animales de Enfermedad , Histona Desacetilasa 6 , Animales , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Histona Desacetilasa 6/genética , Ratones , Humanos , Nervio Ciático , Ratones Noqueados , Eliminación de Gen , Masculino , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/genética , Glicina-ARNt Ligasa/genética , Conducción Nerviosa/fisiología , Conducción Nerviosa/efectos de los fármacosRESUMEN
BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.
Asunto(s)
Anticuerpos Monoclonales , Enfermedades del Sistema Nervioso Periférico , Humanos , Masculino , Femenino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anciano de 80 o más Años , Conducción Nerviosa/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/tratamiento farmacológico , Supervivencia sin Progresión , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patologíaRESUMEN
BACKGROUND: Alpha-lipoic acid, epalrestat, and mecobalamin are widely used as monotherapies for diabetic peripheral neuropathy. However, whether a triple-combination therapy with these three drugs is superior to monotherapy or dual therapy remains debatable. METHODS: Nine randomized controlled trials were identified through a search on electronic databases such as PubMed, Web of Science, and Cochrane Library. The trial participants (N = 1153) were divided into the experimental group who received the triple-combination therapy and the control group who received conventional or dual therapy with the aforementioned drugs. RESULTS: Therapeutic outcomes were better in the experimental group than in the control group (odds ratio: 3.74; 95 % confidence interval: 2.57-5.45; I2 = 0 %; p < 0.00001). No statistic difference was noted in adverse effects. Compared with the control group, the experimental group exhibited significant improvements in median motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and vibration perception thresholds (VPT) in the left and right lower limbs. In the control group, a subgroup analysis by treatment strategy revealed similar improvements in total efficacy, MNCV, and SNCV. CONCLUSIONS: For diabetic peripheral neuropathy, the triple-combination therapy may be more effective than monotherapy or dual therapy.
Asunto(s)
Neuropatías Diabéticas , Quimioterapia Combinada , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido Tióctico , Neuropatías Diabéticas/tratamiento farmacológico , Humanos , Ácido Tióctico/uso terapéutico , Ácido Tióctico/administración & dosificación , Vitamina B 12/uso terapéutico , Vitamina B 12/administración & dosificación , Vitamina B 12/análogos & derivados , Rodanina/análogos & derivados , Rodanina/uso terapéutico , Rodanina/administración & dosificación , Resultado del Tratamiento , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , TiazolidinasRESUMEN
Conotoxins are tools used by marine Conus snails to hunt and are a significant repository for marine drug research. Conotoxins highly selectively coordinate different subtypes of various ion channels, and a few have been used in pain management. Although more than 8000 conotoxin genes have been found, the biological activity and function of most have not yet been examined. In this report, we selected the toxin gene QcMNCL-XIII0.1 from our previous investigation and studied it in vitro. First, we successfully prepared active recombinant QcMNCL-XIII0.1 using a TrxA (Thioredoxin A)-assisted folding expression vector based on genetic engineering technology. Animal experiments showed that the recombinant QcMNCL-XIII0.1 exhibited nerve conduction inhibition similar to that of pethidine hydrochloride. With flow cytometry combined fluorescent probe Fluo-4 AM, we found that 10 ng/µL recombinant QcMNCL-XIII0.1 inhibited the fluorescence intensity by 31.07% in the 293T cell model transfected with Cav3.1, implying an interaction between α1G T-type calcium channel protein and recombinant QcMNCL-XIII0.1. This toxin could be an important drug in biomedical research and medicine for pain control.
Asunto(s)
Canales de Calcio Tipo T/fisiología , Conotoxinas/toxicidad , Conducción Nerviosa/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Animales , Canales de Calcio Tipo T/genética , Línea Celular , Conotoxinas/genética , Caracol Conus , Estimulación Eléctrica , Humanos , Rana catesbeiana , Proteínas Recombinantes/toxicidad , Nervio Ciático/fisiologíaRESUMEN
Fish oil is rich in omega-3 fatty acids and essential for neuronal myelination and maturation. The aim of this study was to investigate whether the use of a mixed-lipid emulsion composed of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF-LE) compared to a pure soybean oil-based lipid emulsion (S-LE) for parenteral nutrition had an impact on neuronal conduction in preterm infants. This study is a retrospective matched cohort study comparing preterm infants <1000 g who received SMOF-LE in comparison to S-LE for parenteral nutrition. Visual evoked potentials (VEPs) were assessed longitudinally from birth until discharge. The latencies of the evoked peaks N2 and P2 were analyzed. The analysis included 76 infants (SMOF-LE: n = 41 and S-LE: n = 35) with 344 VEP measurements (SMOF-LE: n= 191 and S-LE n = 153). Values of N2 and P2 were not significantly different between the SMOF-LE and S-LE groups. A possible better treatment effect in the SMOF-LE group was seen as a trend toward a shorter latency, indicating faster neural conduction at around term-equivalent age. Prospective trials and follow-up studies are necessary in order to evaluate the potential positive effect of SMOF-LE on neuronal conduction and visual pathway maturation.
Asunto(s)
Potenciales Evocados Visuales/efectos de los fármacos , Emulsiones Grasas Intravenosas/administración & dosificación , Emulsiones Grasas Intravenosas/química , Aceites de Pescado/administración & dosificación , Conducción Nerviosa/efectos de los fármacos , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro/fisiología , Masculino , Aceite de Oliva/administración & dosificación , Nutrición Parenteral , Estudios Retrospectivos , Aceite de Soja/administración & dosificación , Triglicéridos/administración & dosificaciónRESUMEN
Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFß-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.
Asunto(s)
Neuropatías Diabéticas/terapia , Suplementos Dietéticos , Conducción Nerviosa/efectos de los fármacos , Tocotrienoles/administración & dosificación , Vitamina E/administración & dosificación , Anciano , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/fisiopatología , Método Doble Ciego , Femenino , Humanos , Masculino , Nervio Mediano/efectos de los fármacos , Persona de Mediana Edad , Neuronas Motoras/efectos de los fármacos , Nervio Sural/efectos de los fármacos , Tibia/inervación , Factor de Crecimiento Transformador beta1/sangre , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
Neuroinflammation contributes significantly to the pathogenesis of diabetic peripheral neuropathy (DPN). Quercetin reportedly exerts neuroprotective effects in DPN. Here, we aimed to evaluate the potential anti-inflammatory effects of quercetin in a DPN rat model. Eight weeks after streptozotocin administration, diabetic rats were treated with quercetin (30 and 60 mg/kg/day orally) for 6 weeks. We assessed the mechanical withdrawal threshold (MWT), nerve conduction velocity (NCV) and morphological changes in sciatic nerves. Additionally, we measured the levels of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and IL-6 by ELISA and the expression of TLR4, MyD88, and NF-κB in sciatic nerves by western blotting and immunohistochemical assays. Our results revealed that blood glucose levels and body weight were unaltered following quercetin treatment. However, quercetin improved MWT (p < 0.05), NCV (p < 0.05), and pathological changes in the sciatic nerves of DPN rats. Quercetin significantly alleviated the increased expression of TNF-α (p < 0.05) and IL-1ß (p < 0.001). Furthermore, high-dose quercetin administration significantly downregulated the expression of TLR4 (p < 0.001), MyD88 (p < 0.001), and NF-κB (p < 0.001) in sciatic nerves of DPN rats. Our findings revealed that quercetin could reduce the levels of inflammatory factors in DPN rats, possibly mediated via the downregulation of the TLR4/MyD88/NF-κB signalling pathway. Collectively, these results suggest that although quercetin did not decreased blood glucose levels or reversed the reduced body weight, it showed anti-inflammatory and neuroprotective effects, which was beneficial for the treatment of DPN.
Asunto(s)
Antiinflamatorios/farmacología , Neuropatías Diabéticas/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Quercetina/farmacología , Receptor Toll-Like 4/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Citocinas/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/metabolismo , Ganglios Espinales/metabolismo , Ganglios Espinales/patología , Inflamación/sangre , Inflamación/metabolismo , Masculino , Conducción Nerviosa/efectos de los fármacos , Enfermedades Neuroinflamatorias/sangre , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Quercetina/uso terapéutico , Ratas Sprague-Dawley , Nervio Ciático/efectos de los fármacos , Nervio Ciático/metabolismo , Nervio Ciático/patología , Nervio Ciático/ultraestructura , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: To assess axonal function prior to subcutaneous immunoglobulin (SCIG) therapy or placebo in relation to relapse in chronic inflammatory demyelinating polyneuropathy (CIDP) to determine whether axonal damage can predict therapy response. METHODS: Relapse rates in patients from the Polyneuropathy and Treatment with Hizentra (PATH) study, where patients were treated with placebo or SCIG (IgPro20), were analyzed by baseline (post-intravenous immunoglobulin stabilization) axonal damage (≤1 mV peroneal compound muscle action potential) status. RESULTS: In patients with non-axonal damage, relapses were significantly higher with placebo (73.0%) than IgPro20 (0.2 g/kg: 39.1%, 0.4 g/kg: 19.2%). In patients with axonal damage, IgPro20 had no effect on relapse (placebo: 25.0%, IgPro20: 0.2 g/kg: 30.0%, 0.4 g/kg: 19.4%). Patients with axonal damage relapsed significantly less on placebo versus non-axonal damage, but they also demonstrated higher baseline disability. CONCLUSION: Axonal damage may correspond to relapse upon treatment withdrawal; patients with axonal damage relapse less, possibly reflecting poor response to immunoglobulin therapy, while non-axonal damage patients may experience more relapse, perhaps indicating better treatment response. SIGNIFICANCE: In CIDP patients with axonal loss, immunoglobulin therapy may not be as effective. Assessing axonal damage could help guide therapy, with immunoglobulins ideally used before substantial axonal damage arises.
Asunto(s)
Inmunización Pasiva/métodos , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Anciano , Estudios de Cohortes , Fenómenos Electrofisiológicos/efectos de los fármacos , Fenómenos Electrofisiológicos/fisiología , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Subcutáneas/métodos , Masculino , Persona de Mediana Edad , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/fisiopatología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4RdlDRN neurons integrate pre-synaptic AgRP signaling, thereby modulating the post-synaptic serotonergic pathway. Specifically, the MC4RdlDRN signaling elicits profound, bi-directional, regulation of body weight mainly through sympathetic outflow that reprograms mitochondrial bioenergetics within brown and beige fat while feeding remains intact. Together, we suggest that this AgRP neural circuit plays a unique role in persistent control of energy expenditure and body weight, hinting next-generation therapeutic approaches for obesity and metabolic disorders.
Asunto(s)
Proteína Relacionada con Agouti/metabolismo , Metabolismo Energético/fisiología , Hipotálamo/metabolismo , Conducción Nerviosa/fisiología , Neuronas Serotoninérgicas/fisiología , Tejido Adiposo Beige/metabolismo , Tejido Adiposo Pardo/metabolismo , Animales , Peso Corporal , Cromatografía Liquida , Ingestión de Alimentos/fisiología , Metabolismo Energético/genética , Masculino , Ratones , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/efectos de la radiación , Obesidad/metabolismo , Optogenética , Receptor de Melanocortina Tipo 4/genética , Receptor de Melanocortina Tipo 4/metabolismo , Neuronas Serotoninérgicas/efectos de los fármacos , Neuronas Serotoninérgicas/efectos de la radiación , Serotonina/metabolismo , Serotonina/fisiología , Transducción de Señal/genética , Transducción de Señal/fisiología , Espectrometría de Masas en Tándem , TemperaturaRESUMEN
BACKGROUND: Recent experimental studies using herbal extracts have shown the possibility of peripheral nerve regeneration. This study aimed to investigate the effects of herbal extracts on peripheral nerve regeneration in a rat sciatic nerve injury model. METHODS: A total of 53 rats were randomly assigned to a control group or one of four experimental groups. In all rats, the sciatic nerve was completely severed and microscopic epineural end-to-end neurorrhaphy was performed. Normal saline (2 mL) was topically applied to the site of nerve repair in the control group, whereas four different herbal extracts - 2 mL each of Astragalus mongholicus Bunge, Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, or Paeonia lactiflora Pall. - were topically applied to the site of nerve repair in each experimental group. Nerve conduction studies were performed at an average of 11.9 weeks after the operation, and conduction velocity and proximal and distal amplitudes were measured. Biopsies were performed at an average of 13.2 weeks after the initial neurorrhaphy. The quality of nerve anastomosis and perineural adhesion to the surrounding soft tissues was macroscopically evaluated. The neuroma size at the site of the neurorrhaphy was microscopically measured, whereas the size of the scar tissue was evaluated relative to the diameter of the repaired nerve. RESULTS: The nerve conduction study results showed the highest nerve conduction velocity in the experimental group that used the Coptis japonica (Thunb.) Makino extract and the highest proximal and distal amplitudes in the experimental group that used the Aconitum carmichaelii Debeaux extract. Macroscopic evaluations after the second operation showed that grade 2 perineural adhesion was found in 70.8% of rats. The mean neuroma size in the Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, and Paeonia lactiflora Pall. groups showed statistically significant decreases relative to the control group. The mean scar tissue formation index in the Paeonia lactiflora Pall. group showed a statistically significant decrease relative to the control group. CONCLUSIONS: The peripheral nerve regeneration effect of the herbal extracts was confirmed through decreased neuroma and scar tissue formation.