Symptoms Of Peripheral Neuropathy Research Articles

Neurological symptoms in adults with Gaucher disease: a systematic review.

Gaucher disease (GD) is classically divided into three types, based on the presence or absence of neurological signs and symptoms. However, presentation can be highly variable in adulthood, and this aspect has not been adequately addressed in the literature so far. We performed a systematic literature review to analyze the entire spectrum of neurological manifestations in adult patients previously classified as GD type I, II, or III, evaluating the role of variants in different neurological manifestations. We searched databases for studies reporting clinical data of adult GD patients (age ≥ 18). Data extraction included GD types, GBA1 variants, age at disease onset and diagnosis, duration of GD, and age at onset and type of neurological symptoms reported. Among 4190 GD patients from 85 studies, 555 exhibited neurological symptoms in adulthood. The median age at evaluation was 46.8years (IQR 26.5), age at neurological symptoms onset was 44years (IQR 35.1), and age at GD clinical onset was 23years (IQR 23.4). Parkinsonism, including Parkinson's disease and Lewy Body dementia, was the most reported neurological manifestation. Other symptoms and signs encompassed oculomotor abnormalities, peripheral neuropathy, seizures, myoclonus, and cerebellar, cognitive and psychiatric symptoms. The genotype N370S/N370S mostly presented with Parkinsonism and the L444P variant with severe and earlier neurological symptoms. The findings of this systematic review highlight: (1) the relevance of a comprehensive neurological assessment in GD patients, and (2) the importance of considering possible undiagnosed GD in adult patients with mild systemic symptoms presenting unexplained neurological symptoms.

Implementation of personalized multidisciplinary neuropathy management program for chemotherapy-induced peripheral neuropathy symptoms in breast cancer patients

Objective To construct a personalized multidisciplinary neurotoxicity management program for chemotherapy-induced peripheral neuropathy (CIPN) symptoms in breast cancer patients and evaluate its application effects. Methods A retrospective analysis was conducted on clinical data of 133 breast cancer chemotherapy patients admitted to our hospital from January 2022 to January 2024. Based on the nursing protocols received, patients were divided into a control group (n = 66) and an intervention group (n = 67). The control group received conventional nursing interventions, while the intervention group received personalized nursing interventions in addition to the control group interventions. The nursing programs were carried out during chemotherapy. A comparison was made between the two groups before chemotherapy and 3 months after chemotherapy in terms of the degree of neuropathy, cancer-related fatigue, negative emotional status, and symptom management knowledge, attitudes, and practices (KAP). Results The intervention group showed significantly lower neuropathy severity (FACT/GOG-Ntx), cancer-related fatigue (CFS), and negative emotions (PHQ-9, GAD-7) scores after chemotherapy compared to the control group (p < 0.05). Additionally, the intervention group exhibited higher scores for symptom management knowledge, beliefs, and behaviors (p < 0.05). Conclusion Personalized multidisciplinary neurotoxicity management program significantly improved neuropathy severity, reduced cancer-related fatigue and negative emotions, and enhanced symptom management knowledge, attitudes, and practices among breast cancer patients undergoing chemotherapy.

Chemotherapy-induced peripheral neuropathy according to biopsychosocial model: A descriptive cross-sectional correlational study

The present study aimed to assess the biological health, perceived well-being and social well-being of cancer patients with CIPN within the scope of the biopsychosocial model. This study was conducted in oncology clinics and outpatient clinics of a research hospital. The sample comprised 109 patients who met the following inclusion criteria: age ≥ 18 years, completed at least three cycles of taxane and platinum chemotherapy treatment, showed peripheral neuropathy symptoms, could communicate in Turkish and provided consent to participate in the study. For data collection, Patient Information Form, Chemotherapy-induced Peripheral Neuropathy Scale (EQRTC QLQ CIPN20), Perceived Well-being Scale and Social Well-being Scale were used. The EQRTC QLQ CIPN20 score was higher in those with high school and higher education than in those with primary school education and below. Perceived well-being was higher with the increase in age, in males, patients receiving only chemotherapy but no immunotherapy, patients without additional stressors, unemployed patients, patients receiving care support from their spouses at home and patients living with their spouses. The social well-being level was higher in those with higher age and number of treatments, those without stem cell transplantation, those without additional stressors, those with primary school education and below and those living alone.

Effect of Endovenous Ablation on Painful Peripheral Neuropathy Symptoms (P6-13.002)

Effect of Endovenous Ablation on Painful Peripheral Neuropathy Symptoms (P6-13.002)

Abstract 126: Effect of active cytomegalovirus infection on symptoms of fatigue, cancer-related cognitive impairment, and peripheral neuropathy in ovarian cancer survivors

Abstract Background: Fatigue, cancer-related cognitive impairment (CRCI) and neuropathy are among the most common and distressing side effects reported by individuals treated with chemotherapy for ovarian cancer. Cytomegalovirus (CMV) is a highly prevalent herpes virus infection worldwide, affects inflammation and immune function, and can reactivate with treatment for cancer. This study aimed to explore the associations between active CMV infection and patient-reported symptoms among ovarian cancer survivors who have completed front-line chemotherapy. Methods: We conducted a cross-sectional study among individuals with a history of a diagnosis of ovarian cancer, primary peritoneal cancer, or fallopian tube cancer from academic and community cancer clinics in Minnesota at any time point after completion of front-line chemotherapy. Participants completed a one-time survey and provided a blood sample. The exposure of interest was plasma CMV DNA level measured using digital PCR, with ≥100 copies/mL of plasma considered active infection (CMV+). We measured symptoms of fatigue (Fatigue Symptom Inventory), CRCI (PROMIS Cognitive Function 8a) and peripheral neuropathy (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity) using validated self-reported measures. Data were analyzed using descriptive statistics and compared by active CMV infection status (CMV+ vs. CMV-) in the full group and by treatment status (receipt of chemotherapy within 30 days prior to data collection) using t-tests. Results: A total of 160 participants were analyzed. Participants were median of 64.0 years old and 2.3 years from initial diagnosis. Most (75.2%) had advanced stage disease, 43.8% had experienced at least one recurrence, and 40.0% received chemotherapy within 30 days prior to participation. Overall, 40.0% were CMV+, with 40.6% CMV+ among those who received chemotherapy within 30 days and 39.6% CMV+ among those who had not. Participants who were CMV+, compared to those who were CMV-, had overall worse symptoms, with greater symptoms of neuropathy in the full group (11.9±9.2 vs. 9.1±7.8, p=0.04) and particularly greater symptoms of CRCI among those who had recently received chemotherapy (29.2±7.4 vs. 33.2±6.7, p=0.03). Conclusion: We identified that active CMV infection is common in this survivor population and found that worse symptoms of neuropathy and CRCI are associated with CMV+ status. These results are consistent with studies among other immune-compromised populations, and with further validation, provide a potential therapeutic path for reducing these symptoms. Citation Format: Xuan Li, Katherine Brown, Kate Honeyfield, Devon Hunter-Schlichting, Morgan Gruner, Deanna Teoh, Melissa Geller, Heather Nelson, Rachel I. Vogel. Effect of active cytomegalovirus infection on symptoms of fatigue, cancer-related cognitive impairment, and peripheral neuropathy in ovarian cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 126.

Lessons in clinical reasoning - pitfalls, myths, and pearls: a case of tarsal tunnel syndrome caused by an intraneural ganglion cyst.

Intraneural ganglionic cysts are non-neoplastic cysts that can cause signs and symptoms of peripheral neuropathy. However, the scarcity of such cases can lead to cognitive biases. Early surgical exploration of space occupying lesions plays an important role in identification and improving the outcomes for intraneural ganglionic cysts. This patient presented with loss of sensation on the right sole with tingling numbness for six months. A diagnosis of tarsal tunnel syndrome was made. Nerve conduction study revealed that the mixed nerve action potential (NAP) was absent in the right medial and lateral plantar nerves. The magnetic resonance imaging (MRI) found a cystic lesion measuring 1.4×1.8×3.8 cm as the presumed cause of the neuropathy. Surgical exploration revealed a ganglionic cyst traversing towards the flexor retinaculum with baby cysts. The latter finding came as a surprise to the treating surgeon and was confirmed to be an intraneural ganglionic cyst based on the histopathology report. Through integrated commentary by a case discussant and reflection by an orthopedician, this case highlights the significance of the availability heuristic, confirmation bias, and anchoring bias in a case of rare disease. Despite diagnostic delays, a medically knowledgeable patient's involvement in their own care lead to a more positive outcome. A fish-bone diagram is provided to visually demonstrate the major factors that contributed to the diagnostic delay. Finally, this case provides clinical teaching points in addition to a pitfall, myth, and pearl related to availability heuristic and the sunk cost fallacy.

Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits, and this process requires the proper recruitment of adaptor molecules to selectively activate downstream pathways. Here, we identified that DOK6, a member of the Dok (downstream of tyrosine kinases) family, is required for the maintenance of peripheral axons, and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice, manifested as impaired sensory, abnormal posture, paw deformities, blocked nerve conduction, and dysmyelination. Furthermore, Dok6 is highly expressed in peripheral neurons but not in Schwann cells, and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding, axon destruction, and hindered retrograde axonal transport. Specifically, DOK6 acts as an adaptor protein for selectivity-mediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and TrkB. DOK6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation, including MAP1B, Tau and Dynein for axonal transport, and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and homeostasis. This finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.

A case report of chronic hepatitis-C genotype 4c infection: Non-specific symptoms can become contextually relevant in clinical diagnosis

Chronic hepatitis C (CHC) infection is one of the leading causes of liver disease worldwide and its early diagnosis is often considered a challenge because of its non-symptomatic presentation until late disease progression stages. We report the case of a 52-year-old, South-Indian male with CHC genotype 4c infection. We start with the patient’s initial presentation 12 weeks before the diagnosis with seemingly non-specific symptoms of pedal edema, purpura, peripheral neuropathy, arthralgia, and recent onset of diabetes mellitus (DM). We then present the employed direct-acting antiviral (DAA) management regimen and the patient’s response over the span of 48 weeks. Correlating with observations from recent literature highlighting CHC’s extra-hepatic role in inducing cryoglobulinemic vasculitis (CV) and pancreatic dysfunction, we discuss some educational perspectives on how CV and DM-related symptoms may sometimes become contextually specific in clinically suspecting, assessing risk, and warranting CHC screening and diagnostic confirmation.

The Effects of an App-Based Physical Activity Program on Colorectal Cancer Patients Undergoing Chemotherapy: A Randomized Controlled Trial.

Colorectal cancer is one of the most common malignancies worldwide. Oxaliplatin, which is used as adjuvant chemotherapy, affects quality of life by causing oxaliplatin-induced peripheral neuropathy in colorectal cancer patients. This study examined the effects of an application (app)-based physical activity program for alleviating peripheral neuropathy symptoms in colorectal cancer patients undergoing chemotherapy. This was a randomized controlled study that included 34 patients undergoing chemotherapy after being diagnosed with colorectal cancer. Outcomes were compared between patients who participated in a 6-week app-based physical activity program (experimental group; n = 17) and who received standard booklet education (control group; n = 17). Data were collected using questionnaires, and exercise time was recorded to evaluate intervention adherence. Significant differences were observed between the groups in peripheral neuropathy symptoms (F = 8.93, P = .002), interference with activities (Z = -2.55, P = .011), and quality of life (F = 7.65, P = .003). The experimental group showed significantly higher average exercise times at 1 to 4 weeks (Z = -2.10, P = .026), 5 to 6 weeks (Z = -4.02, P < .001), and 1 to 6 weeks (Z = -3.40, P = .001) than the control group. The app-based physical activity program had a positive effect on participants' exercise adherence and reduced peripheral neuropathy symptoms. Thus, we propose the adoption of a mobile health app that can be used at any time or place as an intervention for preventing or alleviating adverse effects during the treatment of cancer patients. An app-based physical activity program using the mobile health app can be used as a nursing intervention to manage symptoms and increase the health behavior adherence in cancer patients.

Effect of Sensory Re-Education with Aerobic Training on Sensation and Balance among Diabetic Peripheral Neuropathy Patients: A Pilot Study

Background: People with diabetes have 10 to 30 times higher risk of lower limb amputation than people without thedisease. 85% of non-traumatic amputations in diabetic patients begin with a foot ulcer. Therefore, early interventionis necessary to control the symptoms of diabetic peripheral neuropathy and improve balance. Resistance andaerobic training reduce diabetic symptoms by lowering HbA1C levels. In order to restore functional sensibility,improve adaptive functioning, and improve balance, sensory re-education and aerobics are combined. Therefore,the aim of this study is to find out the effect of Sensory re-education and aerobics on sensation and balance amongdiabetic peripheral neuropathy patients.Purpose: The Purpose of the study is to determine the effects of sensory re-education with aerobic training onsensory perception and balance in Diabetic peripheral neuropathy patients.Material and Method: This study included diabetic individuals of both genders between the ages of 45-60, lowPAR-Q risk scores and Toronto clinical neuropathy scores (TCNS) between 6 and 11. A total of 20 participantswere randomly selected and received sensory re-education with aerobics for six weeks.Results: Individuals with diabetic peripheral neuropathy experienced statistically significant improvement inTCNS from 9.3±1.25 to 4.5± 1.3, in BBS 48.5 ± 2.70 to 41.7±1.41, in TUG 8.12±1.28 to 6.95 ±1.30, with a P value of &lt;0.01.Conclusion: Sensory re-education with aerobic training for 6 weeks of duration reported improvement in sensoryperception and balance among people with diabetic peripheral neuropathy patients.

Exploring the Effectiveness of Ajwain Cream in Treating Taxane-induced Peripheral Neuropathy in Cancer Patients: A Pilot, Randomised and Double-blind Clinical Trial.

Chemotherapy-induced peripheral neuropathy is a common disorder among cancer patients receiving various chemotherapeutic protocols. The present study aimed to explore the feasibility of ajwain (Trachyspermum ammi [L.] Sprague) cream in treating peripheral neuropathy symptoms triggered by taxane chemotherapeutic agents. This was a pilot, double-blind, and randomised clinical trial on patients with peripheral neuropathy attributable to chemotherapy with taxane drugs during 2021-2022 in Tehran. Patients received ajwain or placebo cream for four weeks and filled out the chemotherapy-induced peripheral neuropathy assessment tool (CIPNAT) at the start and end finale of the trial. Side effects were also noted. Thirty patients suffering from breast, lung, gastro-intestinal, or prostate cancer were allocated to each of the drug and placebo groups. The mean difference in CIPNAT score between the groups was 0.83, demonstrating the statistical ineffectiveness of the drug compared with the placebo (P = 0.372). The safety profile showed promising outcomes at the end of the trial. Although the effectiveness of ajwain cream was unacceptable in treating chemotherapy-induced peripheral neuropathy symptoms, multicentre controlled trials with ample sample size are mandatory for an all-inclusive inference.

Debio 1562M, a Next Generation Antibody Drug Conjugate (ADC) Targeting CD37 for AML and MDS Treatment

CD37 is a trans-membrane protein specifically expressed on normal hematopoietic tissues such as B cells, neutrophils and macrophages, and has demonstrated roles in adhesion, cell migration (de Winde et al, 2018; Wee et al, 2015), survival and apoptotic signals (Lapalombella et al, 2012). Increased expression of CD37 has been observed in various hematological cancers such as lymphomas, Chronic Lymphocytic Leukemia (CLL) and Acute Myeloid Leukemia (AML) (Beckwith et al, 2014; Deckert et al, 2013; Pereira et al, 2015; Yan et al, 2021). Higher expression of CD37 was also associated with poor patient outcome in AML (Zhang et al, 2020; Larkin et al, ASH 2018). Debio 1562M is a second-generation novel ADC directed against CD37 and including Debiopharm's proprietary Multilink cleavable linker-payload technology. Multilink improves manufacturing to achieve homogenous high drug antibody ratio while retaining excellent solubility as well as favorable biologic characteristics with preserved internalization kinetics on target cells. Debio 1562M is conjugated to 8 molecules of a tubulin-binding agent and despite cleavable linker that ensure effective intracellular delivery of toxic payload, we show sustained plasma stability in vitro and in vivo with no premature extracellular release. In this work, we report Debio 1562M specificity and potent antitumor activity in multiple AML models both in vitro and in vivo. First, in our in vitro cytotoxicity assay, Debio 1562M displayed nano- to picomolar anti-proliferative activity in both AML cell lines and primary samples. Out of 30 primary samples tested, 20 were sensitive to Debio 1562M with IC50 ranging from 1 to 10nM, this regardless of their mutation status, subtype or medical history. Interestingly, we observed that AML cells have high internalization capability and therefore relatively low levels of surface CD37 is sufficient for cytotoxic activity. The specificity of Debio 1562M was demonstrated by using 3 different CD37 knock out AML cell lines which were generated by CRISPR-Cas9 technology. Parental and CD37 KO cells were treated for 72h with a dose range of Debio 1562M and viability was measured (Figure 1). While Debio 1562M has an IC50 below 1nM in all 3 parental cell lines, its activity is reduced by more than 2 log in the KO cell lines. In vivo, in 3 different AML cell line xenograft mouse models, a single injection of Debio 1562M at 5mg/kg induced complete tumor regression and all mice remained alive at study termination, more than 60 days after treatment, except one mouse in one model. In a patient derived xenograft (PDX) model, the same dose of Debio 1562M significantly reduced tumor burden in blood and bone marrow with sustained activity 42 days after treatment (37% and 98% of blasts in blood and bone marrow respectively in control animals versus 0% and 3% in treated mice, pvalue&amp;lt;0.001). Furthermore, we evaluated the activity of Debio 1562M over venetoclax and azacytidine combination in the MV4-11 Luciferase xenografted mouse model. NCG mice were inoculated with 1x10 7 cells in the tail vein and randomization in groups of 8 mice was performed 14 days later. Mice received either one administration of Debio 1562M at 5mg/kg or a combination of venetoclax (QDx14 100mg/kg) and azacitidine (QDx5 3,5mg/kg). Complete regression of the tumor was observed in all mice after Debio 1562M administration and all mice survived at study termination, 75 days after treatment while none survived after 56 days when treated with venetoclax and azacitidine combination (Figure 2). The toxicology profile of Debio 1562M in mice showed expected clinical signs related to the payload's off target toxicity but with a significant safety margin. Interestingly, no peripheral neuropathy symptoms were detected, as commonly observed for this class of payload. Additionally, Multilink TM-payload construct alone was not associated with any signs of toxicity. On-target toxicity profile couldn't be evaluated as Debio 1562M isn't cross reactive with mouse CD37, however 1 st generation CD37 ADC has already demonstrated safety and tolerability in Phase 1 and 2 clinical trials.Overall, our data confirm the relevance of CD37 targeting for AML treatment. The excellent antitumor activity and tolerability of Debio 1562M in several pre-clinical models now pave the way for upcoming clinical development.

Prospective Study of Acalabrutinib with Rituximab in Patients with Symptomatic Anti-MAG Mediated IgM Peripheral Neuropathy

Background: Peripheral neuropathy (PN) occurs in 20-25% of patients with an IgM paraprotein and up to 50% of these patients have an anti-myelin associated glycoprotein (MAG) antibody which is frequently associated with sensory ataxia and distal limb weakness negatively affecting function and quality of life. While rituximab is active, its activity is limited as a monotherapy and often associated with an IgM flare that can potentiate PN. BTK-inhibitors can block rituximab-associated IgM flare and are proven to markedly reduce serum IgM in Waldenström's Macroglobulinemia (WM). We therefore initiated this trial to evaluate a novel treatment for anti-MAG PN. Methods: We initiateda prospective, single-arm phase II study of acalabrutinib and rituximab (NCT05065554). Patients with an anti-MAG antibody with an IgM monoclonal gammopathy or WM; and a predominantly sensory demyelinating PN with a modified Rankin score of ≥1 with progressive symptoms or a score of ≥2 are eligible. Treatment consists of continuous oral acalabrutinib (100 mg twice daily) with rituximab weekly in cycles 1 and 4. Each cycle is 28 days. The primary endpoint is to evaluate the hematologic response rate. The key secondary endpoint is to evaluate the proportion of patients that achieve improvement or stability in PN based on the Inflammatory Rasch-built Overall Disability Scale (I-RODS) patient-reported disability scale. Additional secondary neurologic endpoints include the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, MRC distal sum score, INCAT sensory sum score, and a neuropathy-specific quality of life scale (IN-QOL). We hypothesize that 75% of participants (H1) will have a hematologic response versus a null (H0) of 50% or lower. With 33 evaluable patients, there will be 82% power to detect a significant difference with an alpha (2-sided) of 0.04. Results: Eight patients, including 4 females, have enrolled as of July 1, 2023. The median age is 70 years (range 65-76), and median ECOG is 1. Median I-RODS score at baseline was 41 (range 23-48; 48 = no disability). All patients have an IgM kappa paraprotein with median baseline serum IgM of 975 mg/dL (range 226-2137), kappa free light chain of 28 mg/L (range 16-47), and M-spike of 0.6 g/dL (range 0.17-1.1). Anti-MAG antibody titer range is 1:70,000 to 1:819,200 IU/L. Bone marrow biopsy showed no disease in 4 patients, a clonal plasma cell population in 1 patient, and lymphoplasmacytic infiltrate in 3 patients. No adenopathy or splenomegaly were detected on baseline CT scans. Six patients (75%) are MYD88 mutated and none CXCR4 mutated. Five patients had prior rituximab therapy and two received prior IVIG. With a median time on treatment of 175 days (range 28-510), the overall response rate among 7 evaluable patients using IWWM-11 criteria was 86%. Categorical responses include 2 very good partial responses (≥90% decrease in IgM, or normalization of IgM with persistent IgM monoclonal protein); 1 partial response (≥50% but &amp;lt;90% decrease in IgM); 3 minor responses (≥25% but &amp;lt;50% decrease in IgM) and 1 stable disease. Four of 7 patients (57%) had improvement in the I-RODS score. Median improvement was 0.5 points (range -4 to 11). One patient was removed from the trial after 28 days due to grade 3 elevation in ALT. Two other reversible grade 3 adverse events occurred including rituximab related infusion reaction and syncope unrelated to treatment. Conclusions: The combination of acalabrutinib and rituximab has demonstrated activity in this first prospective study that is evaluating BTK-inhibition with CD20 directed therapy in patients with IgM related anti-MAG PN. Hematologic responses occurred in 86% of patients and 57% had an improvement in the I-RODS score. Treatment is well tolerated. Additional data from more detailed neurologic assessments are forthcoming. The trial continues to enroll patients. Our findings provide a framework to develop novel, more effective treatment options for anti-MAG PN.

Identifying trajectories and predictors of chemotherapy-induced peripheral neuropathy symptoms, physical functioning, and falls across treatment and recovery in adults treated with neurotoxic chemotherapy: the PATTERN observational study protocol (NCT05790538)

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting side effect of systemic cancer therapy. In many cancer survivors, CIPN persists after treatment ends and is associated with functional impairments, abnormal gait patterns, falls, and diminished quality of life. However, little is known regarding which patients are most likely to develop CIPN symptoms that impair mobility and increase fall risk, when this risk develops, or the optimal timing of early intervention efforts to mitigate the impact of CIPN on functioning and fall risk. This study will address these knowledge gaps by (1) characterizing trajectories of symptoms, functioning, and falls before, during, and after treatment in adults prescribed neurotoxic chemotherapy for cancer; and (2) determining the simplest set of predictors for identifying individuals at risk for CIPN-related functional decline and falls.MethodsWe will enroll 200 participants into a prospective, observational study before initiating chemotherapy and up to 1 year after completing chemotherapy. Eligible participants are aged 40–85 years, diagnosed with stage I-III cancer, and scheduled to receive neurotoxic chemotherapy. We perform objective assessments of vibratory and touch sensation (biothesiometry, tuning fork, monofilament tests), standing and dynamic balance (quiet stance, Timed-Up-and-Go tests), and upper and lower extremity strength (handgrip dynamometry, 5-time repeated chair stand test) in the clinic at baseline, every 4–6 weeks during chemotherapy, and quarterly for 1 year post-chemotherapy. Participants wear devices that passively and continuously measure daily gait quality and physical activity for 1 week after each objective assessment and self-report symptoms (CIPN, insomnia, fatigue, dizziness, pain, cognition, anxiety, and depressive symptoms) and falls via weekly electronic surveys. We will use structural equation modeling, including growth mixture modeling, to examine patterns in trajectories of changes in symptoms, functioning, and falls associated with neurotoxic chemotherapy and then search for distinct risk profiles for CIPN.DiscussionIdentifying simple, early predictors of functional decline and fall risk in adults with cancer receiving neurotoxic chemotherapy will help identify individuals who would benefit from early and targeted interventions to prevent CIPN-related falls and disability.Trial registrationThis study was retrospectively registered with ClinicalTrials.gov (NCT05790538) on 3/30/2023.

The Future of Chemotherapy: The Mechanisms and Benefits of Exercise in Taxane-Induced Peripheral Neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side-effect resulting from numerous neurotoxic chemotherapies that damages the peripheral nerves, alters sensations in the hands and feet, causes burning and shooting pains, and impairs a patient’s quality of life (QoL). There are limited established interventions to help improve CIPN symptoms. There is only one pharmacological agent (Duloxetine) for treatment of CIPN; however, it only has mild benefit, signaling a critical need for alternative management options to manage patient symptoms. Multiple studies suggest therapeutic benefits of exercise in cancer care to improve physical and psychological functioning; however, the benefits regarding CIPN symptoms and physical function are less clear. This narrative review synthesizes research articles investigating the effect and mechanisms induced by different exercise programs for patients with taxane-induced peripheral neuropathy (TIPN) symptoms and function. The overall incidence, manifestations, characteristics, and mechanisms of CIPN are also discussed. While some studies in this narrative review demonstrated that exercise programs may have benefits on sensory and motor TIPN symptoms in some but not all patients, there are consistent benefits of improved QoL and physical function across most patients. This narrative review highlights the need for future research to confirm the effects of exercise for TIPN, with a focus on other important components, including the effect of exercise adherence, type, and supervision level.

Reliability of a novel point of care device for monitoring diabetic peripheral neuropathy

We aimed to assess DPNCheck’s reliability for repeated sural nerve conduction (NC) parameters. This post hoc analysis used data from the randomized controlled ACUDPN trial assessing NC of the N. Suralis every eight weeks over a 6-month period in 62 patients receiving acupuncture against diabetic peripheral neuropathy (DPN) symptoms. The reliability of DPNCheck for nerve conduction velocity and amplitude was assessed using intraclass correlation coefficients (ICC) and was calculated using data from single time points and repeated measures design. The results of the NC measurements were correlated with the Total Neuropathy Score clinical (TNSc). Overall, for both nerve velocity and amplitude, the reliability at each measurement time point can be described as moderate to good and the reliability using repeated measures design can be described as moderate. Nerve velocity and amplitude showed weak correlation with TNSc. DPNCheck’s reliability results question its suitability for monitoring DPN’s progression. Given the limitation of our analysis, a long-term, pre-specified, fully crossed study should be carried out among patients with DPN to fully determine the suitability of the device for DPN progression monitoring. This was the first analysis assessing the reliability of the DPNCheck for DPN progression monitoring using data from multiple collection time points.

The Effectiveness and Safety of Nurse-Led Auricular Acupressure on Chemotherapy-Induced Peripheral Neuropathy Among Patients With Breast Cancer: A Randomized, Double-Blind, Sham-Controlled Trial.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major symptom of distress among chemotherapy-treated cancer survivors. Although various interventions have been attempted, there is no criterion-standard treatment. The aim of this study was to examine the efficacy and safety of auricular acupressure (AA) in improving peripheral neuropathy symptoms in breast cancer patients undergoing taxane-based treatment. A total of 51 eligible participants were enrolled and randomly allocated (1:1) to AA or sham control groups. The intervention was performed weekly for 3 weeks using different ear points, depending on the group. The Total Neuropathy Score was used to measure CIPN objectively. The Numerical Rating Scale and the European Organization for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy-20 were used to measure the subjective symptoms of CIPN. Outcomes were compared between groups by time interaction using generalized estimating equations based on the intention-to-treat principle. Only 1 participant dropped out because of nausea and mild fever. The results of generalized estimating equations showed significant improvement in Numerical Rating Scale scores on the hands and feet and total Chemotherapy-Induced Peripheral Neuropathy-20 in the experimental group compared with the sham control group (all Ps < .05). Although the experimental group showed a greater reduction in Total Neuropathy Score scores than the sham control group, no significant differences were found. Auricular acupressure is an effective and safe nurse-led intervention for managing CIPN symptoms in breast cancer patients. The findings help nurses to integrate AA easily and usefully into nursing care, contributing to managing symptoms of CIPN in cancer patients and survivors.

Evaluating the effect of acupuncture on symptoms of diabetic peripheral neuropathy (DPN) among individuals with diabetic neuropathy: A single-blind, randomized trial study.

This study aimed to investigate the impact of acupuncture on Diabetic peripheral neuropathy (DPN) symptoms among individuals with diabetic neuropathy. In a single-blind, randomized trial conducted between 2019 and 2020, 60 patients diagnosed with diabetic neuropathy were enrolled. These participants were randomly assigned to either the intervention or control group. The intervention group received real acupuncture alongside routine treatment once a week for seven sessions, each lasting 20min. Meanwhile, the control group received sham acupuncture as an adjunct to their routine treatment, following the same schedule. To evaluate treatment efficacy, the study assessed primary outcomes, such as pain intensity measured using the Visual Analogue Scale (VAS). Secondary outcomes included evaluating fatigue severity and diabetic peripheral neuropathy (DPN) side effects, measured using the multidimensional fatigue inventory (MFI-20) and a standard questionnaire after each session. No statistically significant differences in pain and fatigue scores were observed between the two groups throughout all visits, even after adjusting for baseline characteristics, age, sex, type of diabetes, discopathy, and carpal tunnel syndrome parameters (P > 0.05). The findings did not provide strong evidence supporting a significant effect of real acupuncture compared to sham acupuncture on pain and fatigue values (P = 0.267 and 0.634, respectively). However, the 95% confidence interval for pain scores (-0.35, 1.28) was inconclusive, encompassing effect sizes favoring sham acupuncture. Findings suggest that using acupuncture as an adjunctive therapy alongside routine treatment may not lead to a significant reduction in the symptoms of peripheral neuropathy and fatigue severity among individuals with diabetic neuropathy. The online version contains supplementary material available at 10.1007/s40200-023-01314-1.

Vincristine-Induced Peripheral Neuropathy in Children With Malignancy and the Effect of Missed Doses on Treatment Success.

Recognizing the symptoms of vincristine-induced peripheral neuropathy (VIPN) earlier is crucial to preventing the persistent neurological sequelae. The treatment of neuropathy is to discontinue the drug, and the effect of a missed dose of vincristine on treatment success is unclear. This study aims to evaluate VIPN in children with malignancy and the effect of skipping vincristine doses on the treatment success of patients at a single center, retrospectively. Medical records of the children with cancer who received vincristine in our institution between 2013 and 2020 were analyzed retrospectively. Vincristine neuropathy was found in 42 (7%) of 598 pediatric patients who received at least one dose of vincristine during the study period. Neuropathy developed at a statistically significantly lower cumulative dose in patients younger than seven years of age (p=0.04). The mean neuropathy duration of the cases was 8.5 months, and the findings of 40 (95.2%) cases improved. The mean cumulative dose was higher in patients with diffuse nerve involvement. The missed dose of vincristine was lower in the cases in complete remission compared to the other cases and higher doses of vincristine were missed in the stable disease group than in the remission group (p=0.03). VIPN can be encountered in less cumulative doses, mainly in the younger age group. Missed doses of vincristine may affect treatment success, and more comprehensive studies are needed to show this effect more clearly.

A prospective observational study to assess peripheral neuropathy in patients receiving weekly paclitaxel chemotherapy

Background: Peripheral neuropathies are disorders of peripheral nerve cells and fibres. Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment, and it can affect the patient's long-term survival. The prevalence of CIPN is around 38%. Peripheral neurotoxicity (PN) is a side effect of paclitaxel that can lead to treatment discontinuation. The intensity and severity of neuropathy is more with patients receiving weekly paclitaxel chemotherapy. Methods: 60 patients of CA breast receiving weekly paclitaxel monotherapy who fulfilled inclusion and exclusion criteria were enrolled in the study. Clinical examination and grading of neuropathy was done according to NCI-CTCAE version 4.0. All patient had undergone nerve-conduction studies at baseline and 3 months after baseline. Results: 50% of patients, developed signs symptoms of peripheral neuropathy, out of which tingling sensation was the most common symptom (40%). The incidence of grade 1 peripheral neuropathy at 3 and 6 months were 35%, and 31.66%, while grade 2 neuropathy was noted in 18.33%, and 14.75% of patients, respectively. There was a significant difference in the SNAP value between baseline and 3 months for right ulnar nerve, right and left sural nerve and CMAP for right median nerve, right ulnar nerve, right and left tibial nerves which suggests development of neuropathy during 3 months of paclitaxel chemotherapy. Conclusions: This study provides information on the incidence and severity of peripheral neuropathy in patients receiving weekly paclitaxel chemotherapy, which can help physician in further management.