Mild Neuropathy Research Articles

Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma

Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×106/L and was 12 (0, 25)×106/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

Most Carpal Tunnel Releases Address Moderate or Severe Median Neuropathy.

The role of surgery in normal or very mild median neuropathy can be questioned given that surgery in the absence of pathophysiology may offer only nonspecific effects that can be achieved without surgery, which raises ethical concerns. It's also important to avoid misdiagnosis: given that mild median neuropathy is prevalent and generally well-accommodated, notable symptoms from mild median neuropathy can signal unhelpful thoughts and feelings of distress that are a more pressing health priority. We identified 38 studies that categorized electrodiagnostic (EDX) measured median neuropathy severity among people being evaluated for carpal tunnel syndrome. We converted the different EDX grades used into one general grading classification. The Kruskal-Wallis test was used to compare the ratio of moderate/severe to mild/normal EDX findings between tests ordered by a surgeon or a nonoperative clinician. The median (interquartile range) ratio of moderate/severe to mild/normal EDX findings of median neuropathy at the carpal tunnel was 1.2 (0.91 to 1.8) among tests ordered by nonoperative clinicians and 3.3 (1.5 to 5.3) among tests ordered by surgeons (P = .0023). Only 4.1% of the patients who had EDX testing ordered by a surgeon had no measurable neuropathy. There were zero patients with normal EDX findings in 10 of the 17 (59%) studies in surgeon practices and in 10 of the 21 (48%) in the practices of nonoperative clinicians. The observation that in case series documenting EDX severities of median neuropathy, surgeons are mostly treating and operating on moderate to severe pathophysiology, emphasizes that while mild median neuropathy is highly prevalent it is uncommonly considered for surgery. Level II, Prognostic study.

Hidden hearing loss in a Charcot-Marie-Tooth type 1A mouse model.

Hidden hearing loss (HHL), a recently described auditory neuropathy characterized by normal audiometric thresholds but reduced sound-evoked cochlear compound action potentials, has been proposed to contribute to hearing difficulty in noisy environments in people with normal hearing thresholds and has become a widespread complaint. While most studies on HHL pathogenesis have focused on inner hair cell (IHC) synaptopathy, we recently showed that transient auditory nerve (AN) demyelination also causes HHL in mice. To test the effect of myelinopathy on hearing in a clinically relevant model, we studied a mouse model of Charcot-Marie-Tooth type 1A (CMT1A), the most prevalent hereditary peripheral neuropathy in humans. CMT1A mice exhibited the functional hallmarks of HHL together with disorganization of AN heminodes near the IHCs with minor loss of AN fibers. These results support the hypothesis that mild disruptions of AN myelination can cause HHL and that heminodal defects contribute to the alterations in the sound-evoked cochlear compound action potentials seen in this mouse model. Furthermore, these findings suggest that patients with CMT1A or other mild peripheral neuropathies are likely to suffer from HHL. Furthermore, these results suggest that studies of hearing in patients with CMT1A might help develop robust clinical tests for HHL, which are currently lacking.

Prevalence of Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients and Its Effects on Quality of Life: A Survey Study

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment, leading to nerve damage and impairing patients' quality of life.Objective: To evaluate the prevalence of CIPN among cancer patients and its effects on their quality of life.Methods: A cross-sectional study was conducted at Allied Hospital, Pinum Cancer Hospital, and Aziz Fatima Hospital in Faisalabad, Pakistan. The study included 54 cancer patients (20 males, 34 females) aged 13-71 years, undergoing chemotherapy for at least six months. Patients were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy 20-item scale (EORTC-QLQ-CIPN20) and the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS). Data were analyzed using SPSS version 25, with descriptive statistics and chi-square tests performed to evaluate associations.Results: CIPN was prevalent in 90.7% of patients, with mild (59.3%), moderate (27.8%), and severe (3.7%) neuropathy levels. Neuropathy was significantly correlated with reduced quality of life (p = 0.663).Conclusion: CIPN is highly prevalent among cancer patients and significantly affects their quality of life. Early detection and management are crucial to mitigate these effects.

Remote Symptom Alerts and Patient-Reported Outcomes (PROS) in Real-World Breast Cancer Practice: Innovative Data to Derive Symptom Burden and Quality of Life.

Treatment for breast cancer (BC) can lead to debilitating symptoms that can reduce outcomes and quality of life (QoL). Symptom surveillance using a remote symptom monitoring (RSM) platform enables the capture and reporting of patient-reported outcomes (PROs) from home. Women with BC used an RSM platform to complete weekly surveys and report any symptoms experienced during treatment. Symptoms reported as moderate/severe generated alerts to the clinical team. Clinical actions in response to the alert were captured. Results highlighted the value of data generated from a PRO-generated alert system to characterize longitudinal symptom burden and QoL in real-world BC practice, particularly in patients with poor functional status. The most prevalent symptoms that resulted in alerts were pain, nausea/vomiting, neuropathy, fatigue, and constipation. Most women reported one or more moderate/severe symptoms that generated an alert with an average of two alerts per week. Patients with frail status had more alerts, worse QoL and higher treatment bother, indicating that frail patients may benefit from continuous monitoring of symptoms, function, and QoL over time. A case study of patients without pre-existing peripheral neuropathy showed the rapid trajectory from the first report of mild neuropathy until alerts were generated, making a case for early intervention.

Hidden hearing loss in a Charcot-Marie-Tooth type 1A mouse model.

Hidden hearing loss (HHL), a recently described auditory neuropathy characterized by normal audiometric thresholds but reduced sound-evoked cochlear compound action potentials, has been proposed to contribute to hearing difficulty in noisy environments in people with normal hearing thresholds, a widespread complaint. While most studies on HHL pathogenesis have focused on inner hair cell (IHC) synaptopathy, we recently showed that transient auditory nerve (AN) demyelination also causes HHL in mice. To test the impact of myelinopathy on hearing in a clinically relevant model, we studied a mouse model of Charcot-Marie-Tooth type 1A (CMT1A), the most prevalent hereditary peripheral neuropathy in humans. CMT1A mice exhibited the functional hallmarks of HHL together with disorganization of AN heminodes near the IHCs with minor loss of AN fibers. These results support the hypothesis that mild disruptions of AN myelination can cause HHL, and that heminodal defects contribute to the alterations in the sound-evoked cochlear compound action potentials seen in this mouse model. Also, these findings suggest that patients with CMT1A or other mild peripheral neuropathies are likely to suffer from HHL. Furthermore, these results suggest that studies of hearing in CMT1A patients might help develop robust clinical tests for HHL, which are currently lacking.

Comparative Analysis of Diabetic Neuropathy Examination Scores and Nerve Conduction Velocity in Patients with Diabetic Neuropathy

Background: Diabetic neuropathy is a prevalent consequence of diabetes, resulting in substantial morbidity. Precise evaluation is essential for prompt intervention and control. The study assessed the correlation and effectiveness of the Diabetic Neuropathy Examination (DNE) scores and Nerve Conduction Velocity (NCV) as diagnostic tools in individuals with diabetic neuropathy. Methods: An observational research was done, comprising 200 diabetic patients who were diagnosed with diabetic sensory-motor polyneuropathy. Participants completed Dynamic Neuromuscular Examination (DNE) grading and Nerve Conduction Velocity (NCV) testing. The data were analysed using SPSS version 20.0. Results: The study found a considerable negative correlation (r = -0.68, p < 0.001) between DNE scores and NCV results. Higher DNE scores were associated with lower NCV values. Specifically, 20% of participants had mild neuropathy, 40% had moderate neuropathy, and 40% had severe neuropathy according to DNE scores. NCV testing revealed that 65% of participants had abnormal nerve conduction, with 25% showing mild reduction, 25% moderate reduction, and 15% severe reduction. Multivariate regression confirmed that DNE scores are significant predictors of NCV outcomes (Beta = -0.52, p < 0.001), even after adjusting for confounding variables such as gender, age, diabetes duration, and HbA1C levels. Conclusion: DNE scoring is a reliable tool for assessing neuropathy severity in diabetic patients, correlating well with NCV results. Integrating DNE scoring in routine clinical practice can enhance the early detection and management of diabetic neuropathy. Recommendations: Routine use of DNE scoring along with NCV testing is recommended for comprehensive evaluation of diabetic neuropathy. Further research should explore additional diagnostic tools to improve early detection and intervention. Keywords: Diabetic Neuropathy, Diabetic Neuropathy Examination Score, Nerve Conduction Velocity Testing, Diabetic Polyneuropathy, Neuropathy Assessment..

Incidence and Clinical Presentation of Severe Neurotoxicity from Nelarabine in Patients with T-Cell Acute Lymphoblastic Leukemia

BackgroundNelarabine is a purine analog with demonstrated efficacy in the treatment of T-cell Lymphoblastic Leukemia and Lymphoma (T-ALL/LBL). Despite its efficacy and excellent blood-brain barrier penetration, it has a significant side effect profile which is namely concerning for neurotoxicity. Reported neurotoxicity has varied from mild peripheral neuropathy to debilitating grade 4 neurologic complications including Guillain-Barre like syndrome and myelopathy. Patients and MethodsWe conducted a single centered, retrospective case series to study patients who developed severe neurotoxicity after receiving nelarabine as part of T-ALL treatment. One hundred thirty-five patients were identified. Thirteen patients were reviewed for severe neurotoxicity (defined as ≥grade 3), and of those five patients were deemed to have neurotoxicity secondary to nelarabine exposure. ResultsFive patients (4%) developed severe neurotoxicity as manifested by Guillain-Barre like syndrome or myelopathy within a timeframe of eight to fifty-eight days from last nelarabine dose. Upon diagnosis, patients received formal neurologic evaluation by our neuro-oncology specialists including imaging, cerebrospinal fluid testing, and electromyography. Patients were treated with IVIG, and steroids upon diagnosis, but the majority of neuro-deficits were irreversible. ConclusionOur study shows that nelarabine is generally well-tolerated, and the incidence of severe neurotoxicity is rare. Given the potential risk of severe neurotoxicity, we propose capped dose of nelarabine 1000 mg/day, neurological assessment before subsequent dosing, and avoidance of simultaneous IT therapy during nelarabine administration.

Phenotypic spectrum of myelin protein zero-related neuropathies: a large cohort study from five mutation clusters across Italy

BackgroundWe aimed to investigate the clinical features of a large cohort of patients with myelin protein zero (MPZ)-related neuropathy, focusing on the five main mutation clusters across Italy.MethodsWe retrospectively gathered...

Can the 128-Hz tuning fork be an alternative to the biothesiometer for diabetic peripheral neuropathy screening? A cross-sectional study in a tertiary hospital in East India

IntroductionDiabetic neuropathy is frequently underdiagnosed and undertreated. Logistic problems accompany the routine use of the biothesiometer. Hence, we attempted to find a more easily available alternative.Research design and methods149 patients...

Cardiac manifestations of Fabry disease in G3Stg/GlaKO and GlaKO mouse models-Translation to Fabry disease patients.

Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by mutations in the GLA gene encoding alpha-galactosidase A (α-Gal). Loss of α-Gal activity leads to progressive lysosomal accumulation of α-Gal substrate, predominately globotriaosylceramide (Gb3) and its deacylated derivative globotriaosylsphingosine (lyso-Gb3). FD manifestations include early onset neuropathic pain, gastrointestinal symptoms, and later onset life-threatening renal, cardiovascular and cerebrovascular disorders. Current treatments can preserve kidney function but are not very effective in preventing progression of cardiovascular pathology which remains the most common cause of premature death in FD patients. There is a significant need for a translational model that could be used for testing cardiac efficacy of new drugs. Two mouse models of FD have been developed. The α-Gal A-knockout (GlaKO) model is characterized by progressive tissue accumulation of Gb3 and lyso-Gb3 but does not develop any Fabry pathology besides mild peripheral neuropathy. Reports of minor cardiac function abnormalities in GlaKO model are inconsistent between different studies. Recently, G3Stg/GlaKO was generated by crossbreeding GlaKO with transgenic mice expressing human Gb3 synthase. G3Stg/GlaKO demonstrate higher tissue substrate accumulation and develop cellular and tissue pathologies. Functional renal pathology analogous to that found in early stages of FD has also been described in this model. The objective of this study is to characterize cardiac phenotype in GlaKO and G3Stg/GlaKO mice using echocardiography. Longitudinal assessments of cardiac wall thickness, mass and function were performed in GlaKO and wild-type (WT) littermate controls from 5-13 months of age. G3Stg/GlaKO and WT mice were assessed between 27-28 weeks of age due to their shortened lifespan. Several cardiomyopathy characteristics of early Fabry pathology were found in GlaKO mice, including mild cardiomegaly [up-to-25% increase in left ventricular (LV mass)] with no significant LV wall thickening. The LV internal diameter was significantly wider (up-to-24% increase at 9-months), when compared to the age-matched WT. In addition, there were significant increases in the end-systolic, end-diastolic volumes and stroke volume, suggesting volume overload. Significant reduction in Global longitudinal strain (GLS) measuring local myofiber contractility of the LV was also detected at 13-months. Similar GLS reduction was also reported in FD patients. Parameters such as ejection fraction, fractional shortening and cardiac output were either only slightly affected or were not different from controls. On the other hand, some of the cardiac findings in G3Stg/GlaKO mice were inconsistent with Fabry cardiomyopathy seen in FD patients. This could be potentially an artifact of the Gb3 synthase overexpression under a strong ubiquitous promoter. In conclusion, GlaKO mouse model presents mild cardiomegaly, mild cardiac dysfunction, but significant cardiac volume overload and functional changes in GLS that can be used as translational biomarkers to determine cardiac efficacy of novel treatment modalities. The level of tissue Gb3 accumulation in G3Stg/GlaKO mouse more closely recapitulates the level of substrate accumulation in FD patients and may provide better translatability of the efficacy of new therapeutics in clearing pathological substrates from cardiac tissues. But interpretation of the effect of treatment on cardiac structure and function in this model should be approached with caution.

Severity of Neuropathy-Related Disability and Associated Factors of Diabetic Peripheral Neuropathy in a Tertiary Healthcare Center: A Comparative Cross-Sectional Study.

The widespread presence of diabetic peripheral neuropathy (DN) and its related variables among diagnosed diabetes mellitus (DM) patients in Kerala lacks sufficient evidence. The objective of this study was to evaluate the frequency of DN and its related risk variables among those with DM who were receiving care at a tertiary health institution in Kerala. This study was conducted in a tertiary health center in Kerala using a cross-sectional design. The diagnosis of diabetes was established by assessing the glycated hemoglobin A1c (HbA1c) level and the fasting blood glucose (FBG) level. A validated survey questionnaire was employed to gather demographic data as well as the medical history of DM and associated ailments. A thorough physical examination, BMI, and blood pressure were recorded. Dermatological, musculoskeletal, neurological, and vascular assessments were conducted. The subjects were assessed for neuropathy using a neuropathy disability score (NDS). Consequently, those who met the criteria for DM were classified into two groups: those with neuropathy and those without neuropathy. All research participants underwent laboratory examinations such as blood lipid profiles, HbA1c, and vitamin B12 complex concentrations. The study included 200 DM patients; 120 men and 80 women. Study participants were 40-70 years old, with a median age of 53. The prevalence of DN significantly increased with age (p<0.001). The longer a patient had DM, the higher the prevalence of DN, and this variance in percentage was statistically significant (p<0.009) with an OR (odds ratio) of 9.246. A statistically significant 81 (40.5%) of participants graduated, compared to 119 (59.5%) with only higher secondary education or less (OR = 2.042; p = 0.014). Approximately 107 (53.5%) of individuals earned an income under two lakhs, and this disparity was deemed statistically significant (p = 0.003) with an OR of 2.357. In the group of individuals being studied, 53 (26.5%) of them experienced a decrease in pressure sensation, 47 (23.5%) had a decrease or absence of vibration perception, 48 (24%) had an absence or decreased pinprick response, and 46 (23%) had an absent ankle reflex. The study found that the most commonly reported symptoms were tingling (n = 44; 22%), numbness (n = 42; 21%), burning (n = 37; 18.5%), pricking (n = 29; 14.5%), and pain (n = 27; 13.5%). A strong association was found between DN and glycemic status, namely, FBG levels exceeding 140 mg/dL(OR = 4.511, p < 0.001) and HbA1c levels exceeding 6.5% (OR = 3.87, p < 0.001). The prevalence of abnormal vitamin B12 levels in individuals with DN was 63% (p = 0.19), indicating that the finding was not statistically significant. Within the group of individuals with DN being studied, 22% exhibited mild neuropathy, 34% displayed moderate neuropathy, and 44% had severe neuropathy. The DN individuals had significantly reduced ankle dorsiflexion in cases of severe NDS scores compared to those with mild to moderate NDS scores (p = 0.009). During the binary logistic regression analysis, it was shown that the duration of DM (OR = 1.73; p = 0.038) and FBG levels (OR = 2.87; p = 0.018) were determined as predictors for DN. The findings of this study reveal that the duration of diabetes, age, literacy level, income, HbA1c, and FBG were substantially related to a higher likelihood of DN among diabetic patients.

Mitofusin 2 Variant Presenting With a Phenotype of Multiple System Atrophy of Cerebellar Subtype.

To investigate the etiology of cerebellar ataxia in an adult male patient. We performed standard neurologic assessment and genome sequencing of a 62-year-old man with rapidly progressive balance and gait abnormalities. The propositus exhibited cognitive dysfunction, mild appendicular bradykinesia, prominent appendicular ataxia, dysarthria, and hypomimia with minimal dysautonomic symptoms. Nerve conduction studies showed mild peripheral sensory neuropathy and normal motor nerve conduction velocities. Brain imaging showed progressive cerebellar atrophy and gliosis of the olivopontocerebellar fibers, characterized by T2 hyperintensity within the pons. Genetic testing revealed a likely pathogenic germline variant in MFN2 (NM_014874: c.[838C>T];[=], p.(R280C)) in the GTPase domain (G) interface; pathogenic variants of MFN2 typically cause hereditary sensory and motor neuropathy VI or Charcot-Marie-Tooth disease 2A. The presence of progressive ataxia, "hot cross bun" sign, and dysautonomia has been associated with multiple system atrophy, cerebellar type (MSA-C). We describe progressive cerebellar ataxia in an individual with a deleterious variant in MFN2. Our findings suggest that pathogenic variants in MFN2 can result in a spectrum of phenotypes including cerebellar ataxia with cerebellar-pontine atrophy in the absence of significant neuropathy and in a manner closely resembling MSA-C.

Early detection of peripheral neuropathy in patients with diabetes mellitus type 2

BackgroundEarly diagnosis of diabetic polyneuropathy (DPN) can significantly improve the prognosis and help prevent severe complications. The aim of this work was to study clinical, radiological, laboratory and neurophysiological findings for early detection of peripheral neuropathy in T2DM.MethodsA total of 60 diabetic patients were classified according to Toronto Clinical Neuropathy Score (TCNS) into: Group 1: 20 diabetic patients with no evident neuropathy. Group 2: 20 diabetic patients with mild neuropathy. Group 3: 20 diabetic patients with moderate and severe neuropathy. All patients underwent a neurological examination, nerve conduction studies and optical coherence tomography (OCT) to assess retinal nerve fiber layer (RNFL) thickness. Additionally, ELISA technique to measure serum interleukin-6 (IL-6).ResultsThe analysis of gender and age distributions among the groups revealed no significant differences. There were statistically significant differences regarding disease duration, HBA1c, body mass index Systolic and diastolic blood pressure. Group 3 had such significant impairment that resulted in an inability to record the measurements of sural nerves. The study's statistical analysis results for OCT variables, and post hoc comparisons revealed significant differences between all three groups. The results demonstrated significant variations in Serum IL6 levels among the groups, with Group 3 having the highest IL6 levels. In groups 1, 2, and 3 the area under the curve for IL-6 and RNFL showed a good differentiation ability between groups.ConclusionWe conclude that the total thickness RNFL and serum IL-6 levels are a potential biomarker in prediction the severity of DPN.

Experience of using mCRL in patients with drug-resistant TB and evaluation of treatment effectiveness and adverse effects

Objective. To study the frequency of adverse events when using new drugs in the treatment regimen for patients with MDR-TB and evaluate the effectiveness of new shorter regimens. Material and methods of research. New shortened regimens have been used for the treatment of patients with MDRTB since September and February 2020 in two institutions (MJ and GS). 225 MDR cases were identified in the treatment regimens, Bdq, Lzd, Lfx, Cfz, Cs were prescribed to 106 patients. Gender balance: men 58 (67.4%), women 28 (32.56%). Almost 67 (79.76%) patients had a bilateral process with decay cavities, and 17 (20.24%) patients had a process without decay. The main side effect of bedaquiline is cardiotoxicity, which manifests itself in prolongation of the QT interval and an increase in QTcF (Fridericia coefficient) calculated using the Fridericia formula. The cardiotoxicity of bedaquiline persists after taking it for another 6 months, i.e. has a cumulative effect. In this connection, with the use of bedaquiline in treatment regimens, an electrocardiographic (ECG) study is initially performed. When monitoring treatment with bedaquiline in the first month, an ECG study is performed after 14 days, before the end of the course of treatment is carried out monthly, after the end of the course for 3 months. SAEs were identified in 3 patients. Hypokalemia, myelosuppression and hyperglycemia were noted accordingly in the 1 patient Peripheral neuropathy (moderate) was observed in 7 patients. Results. Culture conversion was observed in 63 patients (75%) who took Bdq, Lzd, Lfx, Cfz, Cs treatment regimens for 9 months. Time to culture conversion was ≤ mean (or median) in 10 (25%) cases, ≥ mean (or median) in 97 (75%) cases In the remaining 16 (18%) patients, the isolation of mycobacteria persisted, and additional detection of resistance to the main drugs provided a rationale for prolonging the course of treatment. In 5 patients dropped out, these patients were discharged for violations of the nosocomial regimen and took drugs only from 28 days to 2 months. There was no prolongation of the QT interval (0.48-0.51 s). All continued the course with bedaquiline. Peripheral neuropathy (moderate) occurred in 7 (8%) patients taking linezolid. All patients (with mild neuropathy) continued the course with linezolid. These patients were prescribed pyridoxine until the end of the regimen. Myelosuppression was observed in 59 patients. 10 of them had grade 1, 3 had grade 2, and only 1 had grade 3 myelosuppression. Nearly all of those treated with clofozemin had a dark brown skin tone. Treatment outcomes and course completion were 63(75%), failure 16(19%). Conclusion. The effectiveness of shortened treatment regimens for MDR/TB patients with the inclusion of new antiTB drugs (Bdq, Lzd, Lfx, Cfz, Cs) in the treatment regimen turned out to be quite high, side effects were eliminated in time with the help of careful monitoring. In earlier terms, sputum conversion and closure of decay cavities were noted.

Lidocaine Infusion Versus Duloxetine for Prevention and Management of Taxane-Induced Peripheral Neuropathy among Breast Cancer Patients-A Randomized Controlled Study

BACKGROUND: Taxane-induced peripheral neuropathy (TIPN) among breast cancer patients is considered one of the most devastating side effects affecting compliance to chemotherapy protocol and patients’ quality of life (QOL). OBJECTIVES: This trial aimed to evaluate the effect of lidocaine infusion vs oral duloxetine on the incidence and severity of TIPN and QOL in patients with breast cancer scheduled for neoadjuvant taxane therapy (TT). STUDY DESIGN: Prospective, randomized, single-blinded, controlled trial. SETTING: This study was carried out on 60 patients with breast cancer scheduled for 12 weeks of TT at the Medical Research Institute Hospital, Alexandria University after obtaining local Ethics Committee approval (IORG008812) and getting a written informed consent from each patient. It was registered in the “clinical trials library for protocol registration and results system” with the number NCT04732455. METHODS: Sixty women scheduled for TT weekly for 12 weeks, were randomly allocated to receive intravenous saline infusion in the control group (GC), or lidocaine 2mg/kg with saline infusion in the lidocaine group (GL), or saline infusion and 30 mg duloxetine in the duloxetine group (GD). All infusions were administered over 40 minutes before each TT. Oral duloxetine was prescribed once daily starting from the night before commencing TT and continued for 12 weeks. Douleur Neuropathique en 4 Questions (DN4) questionnaire was filled weekly to detect the incidence of neuropathic pain (NP). The nerve conduction study (NCS) aimed to detect and measure the degree of neuropathy before starting the chemotherapy protocol and post-12 weeks of Taxol Therapy. NP Scale was measured weekly to assess the severity of NP symptoms. Patients’ QOL was evaluated by the European Organization for Research and Treatment of Cancer QOL Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-Item Scale. RESULTS: Thirty-five percent of patients reported DN4 &gt; 4 points in GC after 6 weeks of TT in comparison to 5% in GL and 0% in GD (P = .005). Moreover, the incidence rose to 75% in GC compared to 20% in GL and 25% GD at the end of TT (P &lt; 0.001). The severity of symptoms, global pain intensity, and patients’ unpleasantness were significantly more in GC than GL and GD in the last 4 weeks of TT (P &lt; 0.05). NCS showed that 55% and 25% of patients developed mild and moderate axonal neuropathy, respectively, in GC. In contrast, mild neuropathy was developed in 20% and 25% of patients in GL and GD, respectively, and moderate neuropathy in 5% in both groups. The negative impact of TT on QOL was more significant in GC than GL and GD at weeks 8 and 12 of TT (P &lt; 0.001). LIMITATIONS: Limited reference data for all treatment regimens to include in the Discussion section. CONCLUSIONS: Lidocaine and duloxetine have a comparable effect to decrease the incidence and severity of TIPN. Moreover, patients’ QOL was significantly better in both groups. KEY WORDS: Lidocaine infusion, duloxetine, taxane-induced peripheral neuropathy, breast cancer, DN4

Rare PMP22 variants in mild to severe neuropathy uncorrelated to plasma GDF15 or neurofilament light

Charcot-Marie-Tooth disease (CMT) is a heterogeneous set of hereditary neuropathies whose genetic causes are not fully understood. Here, we characterize three previously unknown variants in PMP22 and assess their effect on the recently described potential CMT biomarkers’ growth differentiation factor 15 (GDF15) and neurofilament light (NFL): first, a heterozygous PMP22 c.178G > A (p.Glu60Lys) in one mother-son pair with adult-onset mild axonal neuropathy. The variant led to abnormal splicing, confirmed in fibroblasts by reverse transcription PCR. Second, a de novo PMP22 c.35A > C (p.His12Pro), and third, a heterozygous 3.2 kb deletion predicting loss of exon 4. The latter two had severe CMT and ultrasonography showing strong nerve enlargement similar to a previous case of exon 4 loss due to a larger deletion. We further studied patients with PMP22 duplication (CMT1A) finding slightly elevated plasma NFL, as measured by the single molecule array immunoassay (SIMOA). In addition, plasma GDF15, as measured by ELISA, correlated with symptom severity for CMT1A. However, in the severely affected individuals with PMP22 exon 4 deletion or p.His12Pro, these biomarkers were within the range of variability of CMT1A and controls, although they had more pronounced nerve hypertrophy. This study adds p.His12Pro and confirms PMP22 exon 4 deletion as causes of severe CMT, whereas the previously unknown splice variant p.Glu60Lys leads to mild axonal neuropathy. Our results suggest that GDF15 and NFL do not distinguish CMT1A from advanced hypertrophic neuropathy caused by rare PMP22 variants.

OVERVIEW OF PERIPHERAL NEUROPATHY IN CHRONIC KIDNEY DISEASE PATIENTS UNDERGOING HEMODIALYSIS AT DR. MOHAMMAD HOESIN HOSPITAL PALEMBANG

Neurological complications occur in almost 60% of patients with advanced CKD and affect the nervous system at all levels, both central and peripheral. Peripheral neuropathy in CKD is usually asymptomatic until renal function is below 15%, and glomerular filtration is less than 10-12 ml/min. This study seeks to identify and characterize peripheral neuropathy in patients with chronic kidney disease undergoing hemodialysis at Dr. Mohammad Hoesin Hospital Palembang. This is a descriptive cross-sectional study with the research sample comprising chronic kidney disease patients undergoing hemodialysis at Dr. Mohommad Hoesin Palembang Hospital. The distribution of research subjects based on the Neuropathy Symptom Score (NSS) revealed that 65.7% fell into the mild neuropathy category, based on an NSS of 3-4. According to the electrophysiology results, 82.9% of patients exhibited peripheral neuropathy, while 17.1% showed normal NCS results. Sensory motor neuropathy accounted for 51.4%, including 71.5% with axonal neuropathy, 11.4% with axonal-demyelinating lesions, and no demyelinating lesions. The high prevalence of peripheral neuropathy in CKD patients identified through electrophysiological examination (ENMG) emphasizes the importance of nerve conduction examination as a diagnostic tool for peripheral neuropathy in CKD patients. This can aid in determining the progression of peripheral neuropathy in CKD patients, allowing for appropriate management and prevention of disability complications to enhance the quality of life for these individuals.

Diagnosis of Mild-to-moderate Idiopathic Median Neuropathy at the Carpal Tunnel Based on Signs and Symptoms is Discordant From Diagnosis Based on Electrodiagnostic Studies and Ultrasound.

Although idiopathic median neuropathy at the carpal tunnel (IMNCT) is objective and verifiable, distinction of normal and abnormal nerves is imprecise and probabilistic. The associated symptoms and signs (carpal tunnel syndrome [CTS]) vary, particularly for nonsevere (mild and moderate) median neuropathy. Discordance between diagnosis of mild or moderate median neuropathy at the carpal tunnel using symptoms and signs and diagnosis based on objective tests is a measure of the potential for overdiagnosis and overtreatment. What is the difference in the estimated prevalence of mild-to-moderate IMNCT using nonsevere signs and symptoms compared with the estimated prevalence using electrodiagnostic studies (EDS) and ultrasound (US)? We used data from an existing cross-sectional data registry. To create this registry, between January 2014 and January 2019, we considered all new adult English-speaking people who had an EDS that included the median nerve or people with a diagnosis of CTS who did not have surgery yet. A small and unrecorded number of people declined participation. The cross-sectional area of the median nerve at the distal wrist crease using US in people who already had EDS was measured. People with a diagnosis of CTS underwent both EDS and US. The six signs and symptoms of Carpal Tunnel Syndrome 6 (CTS-6, a validated tool to estimate the probability of IMNCT using ratings of symptoms and signs of CTS) were recorded. This resulted in a registry of 185 participants; we excluded 75 people for obvious, severe IMNCT (defined as nonrecordable nerve conduction velocity, thenar atrophy, or greater than 5 mm 2-point discrimination). Three of the 110 qualifying patients had missing information on ethnicity or race, but we accounted for this in our final analysis. Without a reference standard, as is the case with IMNCT, latent class analysis (LCA) can be used to establish the probability that an individual has specific pathophysiologic findings. LCA is a statistical method that identifies sets of characteristics that tend to group together. This technique has been used, for example, in diagnosing true scaphoid fractures among suspected fractures based on a combination of demographic, injury, examination, and radiologic variables. The prevalence of mild-to-moderate IMNCT was estimated in two LCAs using four signs and symptoms characteristic of mild-to-moderate IMNCT, as well as EDS and US measures of median neuropathy. The estimated prevalence of mild-to-moderate IMNCT based on signs and symptoms was 73% (95% CI 62% to 81%), while the estimated prevalence using EDS and US measurements was 51% (95% CI 37% to 65%). The notable discordance of 22% between the estimated prevalence of mild-to-moderate IMNCT using signs and symptoms and prevalence based on EDS and US criteria, and the overlapping CIs of the probability estimations, indicate considerable uncertainty and a corresponding notable potential for underdiagnosis or overdiagnosis. When signs and symptoms suggest mild-to-moderate median neuropathy and surgery is being considered, patients and clinicians might consider additional testing, such as EDS or US, to increase the probability of actual median neuropathy that can benefit from surgery. We might benefit from a more accurate and reliable diagnostic strategy or tool for mild-to-moderate IMNCT; this might be the focus of a future study. Level III, diagnostic study.

Prevalence and risk factors of peripheral neuropathy among young type 2 diabetes mellitus patients attending a tertiary care hospital in upper Assam: A cross-sectional study

Abstract Background: Diabetic peripheral neuropathy (DPN), being the most common and early complication of diabetes mellitus, results in significant morbidity and debilitating sequelae in the form of foot ulcers, infection, and amputation. Due to the disease’s longevity, young type 2 diabetes constitutes a high risk for developing neuropathy, and screening of patients for DPN becomes crucial. Objectives: This study aimed to estimate the prevalence and identify the associated risk factors of peripheral neuropathy among young type 2 diabetes mellitus patients attending a tertiary care hospital in upper Assam. Materials and Methods: This cross-sectional study was conducted from July 1, 2022 to September 30, 2022 in the Department of Medicine. A total of 165 participants attending the outpatient Department and the Diabetic clinic, diagnosed with type 2 diabetes below the age of 45 years were recruited using non-random consecutive sampling. Patients were then interviewed using a pre-designed, pre-tested schedule. DPN was assessed by detection of vibration perception threshold (VPT) using a biothesiometer, the cutoff value for which was taken as 15 V. Results: The prevalence of DPN as assessed by VPT using biothesiometer was 13.9%. The prevalence of mild, moderate, and severe neuropathies was 9.1%, 3.6%, and 1.2%, respectively. DPN was found to have a significant association with the duration of diabetes and hypertension. Socio-demographic characteristics, smoking, alcohol intake, physical activity, anti-diabetic medication, and dyslipidemia were not found to have a significant association with DPN. Conclusion: This study has stressed the importance of screening for hypertension even in the younger age groups as well as the need for early detection of DPN, which can aid in taking necessary actions to impede the disease’s progression.