Neuropathic Symptoms In Patients Research Articles

Home-based high tone therapy may alleviate chemotherapy-induced neuropathic symptoms in patients with colorectal cancer: A randomized double-blind placebo-controlled pilot evaluation

BackgroundMost oncologic patients receiving chemotherapy suffer from neuropathy, which not only severely affects quality of life but also may lead to chemotherapy dose reductions or even discontinuation of cancer therapy. Still, it is difficult to sufficiently control these symptoms with the currently available pharmacological treatments. High tone therapy was reported to be an effective option for neuropathies due to different etiologies. However, to date, there are no studies on high tone therapy in patients with chemotherapy-induced peripheral neuropathy.MethodsThis randomized, double-blind, and placebo-controlled two-center study was conducted at the Departments of Physical and Rehabilitation Medicine at the Clinics Donaustadt and Ottakring, Vienna, Austria. Patients with histologically verified colorectal carcinoma treated with a platin derivate and neuropathic symptoms were invited to participate. High tone therapy took place in a home-based setting using the HiToP 191 PNP ® or placebo device for three weeks. Neuropathic symptoms and quality of life were assessed via questionnaires. After the follow-up examination, an opt-in was offered to the patients in the placebo group in terms of an open-label treatment with a verum HiToP PNP ® device.In addition, patients with chemotherapy-induced peripheral neuropathy due to various malignant diseases were treated in an open-label setting reflecting a clinical application observation. These patients are reported as a separate group.ResultsIn the verum group, there was a significant reduction of paresthesias and mental stress due to paresthesias from baseline until end of therapy, compared to placebo. These findings were observed in the opt-in subgroup, as well. In the open-label clinical application observation group, intensity and mental stress due to paresthesia, pain, cramps, and intensity of tightness/pressure were significantly lower at the end of therapy, compared to baseline.ConclusionsHome-based high tone therapy brought about a significant alleviation in paresthesias and mental stress due to paresthesias in the verum but not the placebo group. In the clinical application observation, a significant alleviation in several further neuropathic symptoms was seen.Trial registrationThis study was registered at clinicaltrials.gov (NCT06048471, 03/02/2020).

Effect of Aerobic Exercise with and without Strengthening Exercises on Neuropathic Symptoms in People with Diabetic Peripheral Neuropathy

Background: The incidence of peripheral neuropathy among chronic diabetic patients is escalating, with a notable rise observed in Pakistan. This trend has been partly attributed to the predominant reliance on pharmacotherapy, while the role of physical exercise in management remains underutilized. Aerobic exercise is widely recommended in clinical guidelines for the treatment and prevention of diabetic complications, and it is hypothesized that the addition of strength training could yield even more benefits. Objective: This study aimed to evaluate the effects of combined aerobic and strength training exercises on neuropathic symptoms in patients with diabetic peripheral neuropathy. Methods: In this randomized clinical trial, 40 patients with diabetic peripheral neuropathy were equally divided into two groups: Group A underwent a combined regimen of aerobic and strength training exercises, whereas Group B engaged in aerobic exercises alone. The effectiveness of these interventions was assessed using the Michigan Neuropathy Screening Instrument (MNSI), Numeric Pain Rating Scale (NPRS), and Clinical Global Impression of Change (CGIC). Data were analyzed using SPSS version 20.0, employing independent t-tests, repeated measures ANOVA, and descriptive statistics for in-depth analysis. Results: Group A demonstrated a significant reduction in MNSI scores with a mean difference of 1.700 and a p-value < 0.001, indicating a substantial improvement in neuropathic symptoms compared to Group B. While both groups showed significant improvements in NPRS and CGIC scores, the differences were not statistically significant, with p-values of 0.599 and 0.330, respectively, and mean differences of 0.1500 and 0.2500 for NPRS and CGIC. The overall statistical analysis revealed a high significance level (p < 0.001) within both groups in all measured outcomes, suggesting considerable improvements post-intervention. Conclusion: The addition of strength training to aerobic exercises significantly enhances the reduction of neuropathic symptoms in diabetic patients. However, for pain relief and overall clinical improvement, both treatment approaches—combined aerobic and strength training or aerobic exercise alone—were equally effective.

Autonomic neuropathic symptoms in patients with diabetes: practical tools for screening in daily routine

BackgroundDiabetic autonomic neuropathy (DAN) is a frequent complication in people with diabetes whose screening is often neglected. This study aimed to evaluate DAN through practical tools in people with diabetes in a referral center for diabetes treatment.MethodsDAN symptoms and severity were assessed using the Survey of Autonomic Symptoms (SAS) via digital application (app) in patients attended from June 1, 2021, to November 12, 2021. SAS scoring for DAN was performed using established validated cutoffs. The adhesive with cobalt salt color indicator (Neuropad™) was used as a measure of sudomotor dysfunction. Demographical and clinical data were also collected.ResultsData from 109 participants, 66.9% T2DM, 73.4% female, with a median age of 54.00 (± 20.00) years, were analyzed. Symptomatic DAN was present in 69.7% of participants and was associated with older age (p = 0.002), higher HbA1c (p = 0.043), higher abdominal circumference (p = 0.019), higher BMI (p = 0.013), more likely to have metabolic syndrome (MS) with a 10-fold increased risk, and more frequent association with diabetic peripheral neuropathy (p = 0.005). Sudomotor dysfunction was found in 65 participants with positive Neuropad™ detected in 63.1% of them.ConclusionThe use of SAS through an app proved to be a practical and easy-to-use instrument to document symptoms of DAN in busy clinical practice. The high frequency of symptoms draws attention to the importance of screening this underdiagnosed diabetes complication. The risk factors and comorbidities associated with symptomatic DAN highlight the patients’ phenotypes linked to MS that should be targeted for DAN evaluations in larger samples in the community.

Effectiveness of Empagliflozin With Vitamin D Supplementation in Peripheral Neuropathy in Type 2 Diabetic Patients.

Background: Neuropathy is the most prevalent broad-spectrum microvascular complication of diabetes. The present study aims to evaluate the effect of empagliflozin with vitamin D supplementation on diabetic peripheral neuropathy.Methods: A prospective, randomized, controlled study was conducted for six months including 150 type 2 diabetic patients, divided into three groups (n=50/group): Group 1, patients on oral hypoglycemic agents; Group 2, patients on empagliflozin and Group 3, patients on empagliflozin with vitamin D. Biochemical parameters were estimated for outcome measurements and patients’ neuropathic pain was analysed using Douleur Neuropathique 4 Questions, Neuropathic Pain Symptom Inventory and Ipswich Touch the toes test questionnaire. Data were analysed using a one-way analysis of variance.Results: Diabetic neuropathy in males was more prevalent (more than 50%) as compared to females in all three groups, with an average age of 50±6 years, along with a diabetic history of 15±4.5 years and a glycated hemoglobin A1C (HbA1C) level of >10%. The mean value of serum vitamin D level significantly increased by 64.7% (19±5 to 54±8 ng/mL; p<0.05). A remarkable decrease (by 17.4%) from baseline in the HbA1C level was observed after six months of treatment only in Group 3, whereas in other groups (1 and 2), there was a non-significant decrease in HbA1C levels when compared to baseline. Moreover, a significant improvement in neuropathic condition was seen only in Group 3.Conclusion: The results indicated that empagliflozin with vitamin D supplementation significantly controlled or reduced HbA1C and improved diabetic neuropathic symptoms in patients. It is suggested that this combination can be considered as the primary therapeutic approach for neuropathic complications in diabetic patients.

Effect of peer support on adults with diabetes-related peripheral neuropathy

ObjectiveTo explore the effect of peer support on exercise self-efficacy, physical activity level, and neuropathic symptoms in patients with diabetes-related peripheral neuropathy (DPN). MethodsA total of 60 adults with DPN were assigned to groups. Patients in the control group received routine education (RE), while patients in the intervention group received peer support (PS) combined with routine diabetes education. Data were collected at baseline and after intervention (12 weeks). ResultsAt 12 weeks, better outcomes were found in the PS group compared to the RE group for the following aspects: exercise self-efficacy, steps, total physical activity, fasting blood glucose and 2-hour postprandial blood glucose. Decreases in scores on Toronto Clinical Scoring System occurred between baseline and post-intervention in both groups. ConclusionPeer support is an effective way to improve exercise self-efficacy, number of steps, and general physical activity and to reduce blood glucose for patients with DPN. But the effects of peer support on neuropathic symptoms is are obvious. Further research is needed. Practice implicationsAs a low-cost, effective education approach, peer support strategies should be integrated into our healthcare system to meet the minimum needs of patients with DPN.

The increase of neuropathic symptoms in diabetic patients is related with osteopenia.

To investigate the relationship between the intensity of neuropathic pain and the severity of osteopenia in type 2 diabetic patients with painful diabetic peripheral neuropathy (painful DPN). In 220 patients with type 2 diabetes included in the screening, the presence of neuropathic pain was evaluated using the Douleur Neuropathique 4 Questions (DN4) scoring system. One hundred forty-five patients with painful DPN were identified and included in the study. Socio-demographic and laboratory evaluations were made and bone mineral density (BMD) of these patients was evaluated by the dual-energy x-ray absorptiometry (DEXA) method. There was a significant correlation between the neuropathic pain score and the total T scores of the lumbar spine and femur in patients with painful DPN. According to the regression analysis (standard coefficients), the DN4 score (0.498); the level of vitamin D (- 0.246) and the female sex (0.236) for the lumbar spine region; age (0.387); DN4 score (0.261); and vitamin D level (- 0.155) for the femur region were independently influencing factors on the development of osteoporosis. When osteoporosis (T score ≤ - 2.5) of the lumbar spine was analyzed by binary logistic regression, the risk of osteoporosis in women was 4.4 times higher, and the risk increased with increasing DN4 score. The increase of neuropathic symptoms in patients with DPN is an effective and important factor in the development of diabetic osteopenia.

Bilateral C5 palsy after posterior cervical spine decompression surgery: A case report and literature review

C5 palsy is a well-known complication following cervical spine surgery. We describe a case of a 68-year-old male who underwent C3 to C6 posterior instrumentation and fusion with laminectomy and C7 hemilaminectomy for severe multilevel cervical stenosis. This is complicated by severe bilateral C5 palsy and neuropathic symptoms postoperatively, which improved with conservative management and acupuncture. This is the first described case of acupuncture being used in the treatment of C5 palsy. Further studies are needed to determine the efficacy of acupuncture in the management of neuropathic symptoms in patients with C5 palsy.

Cycle Training improves vascular function and neuropathic symptoms in patients with type 2 diabetes and peripheral neuropathy: A randomized controlled trial.

Diabetic peripheral neuropathy (DPN) is associated with peripheral arterial disease and endothelial dysfunction. We investigated the effect of exercise training on the measures of superficial femoral artery (SFA) and neuropathic symptoms in patients with DPN. In a randomized-controlled trial, 31 volunteers with established DPN were randomly assigned to experimental or control groups. Experimental group performed cycling exercise training (50%-70% of heart rate reserve, 30-45min, 3 sessions/week) over 12weeks. Before and 48h after the experimental period a 5-min flow mediated dilation (FMD) response in SFA using Color Doppler Ultrasonography, fasting glucose level, HbA1c and neuropathic score were assessed. FMD% significantly increased in the experimental group (from 3.2±1.1% to 5.7±1.2%) compared to the control condition (P=0.0001). However, no significant alteration occurred in baseline membrane diameter and intima media thickness (P>0.05). We also observed a significant improvement in fasting glucose, HbA1c and Michigan Diabetic Neuropathy Score (MDNS) following exercise intervention (all P<0.05). Linear regression analysis indicated that the change in MDNS was significantly associated with the change in HbA1c (R Square=0.34, standardized coefficients Beta=-0.58, P=.001) and FMD (R Square=0.37, standardized coefficients Beta=0.61, P=.001). This finding may be clinically of considerable importance as metabolic and vascular factors have been indicated to be involved in the development of DPN.

Biomarkers of response to alpha-lipoic acid ± palmitoiletanolamide treatment in patients with diabetes and symptoms of peripheral neuropathy.

To evaluate the effect of oral alpha-lipoic acid (ALA) ± palmitoyl-ethanolamide (PEA) on neuropathic symptoms in patients with diabetic peripheral neuropathy (DPN) and to identify factors related to the efficacy of the treatment. This is a retrospective observational pilot study evaluating 49 patients with diabetes and positive Neuropathy Symptoms Score (NSS). Clinical and biochemical variables, including NSS, were compared between untreated patients and patients treated with oral 600 mg/day ALA ± 600 mg/day PEA at baseline (first occurrence of NSS ≥ 3) and at least 2 months after baseline. Number of days between treatment initiation and symptoms' relief and related factors were also investigated. Thirty subjects were treated with ALA ± PEA and 19 subjects did not receive any specific treatment for neuropathy symptoms. Follow-up visits occurred after 98 ± 46 days. NSS significantly decreased in patients treated with ALA ± PEA (5.4 ± 1.3 at baseline vs. 1.7 ± 2.4 at follow-up, p < 0.001), but not in untreated patients (p = 0.164). Subjects treated with ALA ± PEA reported a mean time from treatment initiation to symptoms' relief of 18.4 ± 9.0 days. The number of days of treatment needed for symptoms' relief was inversely related to HDL-cholesterol levels (r = -0.503, p = 0.010) and to eGFR (r = -0.428, p = 0.033), whereas there was no significant relationship between time to symptoms' relief and age, HbA1c, lipid profile and the severity of symptoms at baseline. This study documents that oral administration of ALA ± PEA helps in controlling neuropathy symptoms in diabetes. Moreover, our data show that higher HDL-c levels and better renal function are associated to a faster therapeutic effect, suggesting them as biomarkers of response to therapy with ALA ± PEA.

Neuropathic Symptoms in World Trade Center Disaster Survivors and Responders.

The objective of this research is to determine whether responders and survivors of the World Trade Center (WTC) disaster experience symptoms of neuropathy at a rate higher than those not exposed. A survey of neuropathic symptoms in patients who were and were not exposed at the WTC based upon the Michigan Neuropathy Screening Instrument (MNSI). Even after correction for medical comorbidities, age, and depression, neuropathic symptoms are much more common in those exposed to WTC dust and increase with increasing exposure. This study provides evidence that exposure to WTC dust is associated with neuropathic symptoms.

Prevalence of neuropathic symptoms in patients referred for temporomandibular disorder in a Chilean hospital, 2014-2015.

Aim: To determine the prevalence of neuropathic symptoms in the orofacial region in patients referred for painful temporomandibular disorder at Hospital Base Valdivia in 2014 and 2015.Materials and method: An observational study was conducted on patients referred for painful temporomandibular disorder by general dentists working in primary dental health care at Hospital Base Valdivia, during October 2014 and March and April 2015. Patients were asked to complete the LANSS pain scale by one of the examiners. The variables age, sex and location of pain were measured and registered. Results: Of the 84 patients surveyed, 88.1% were women, with a mean age of 38.2 years. The median score obtained with the LANSS scale was 3.0 [0-8.75]. A 20.2% had neuropathic pain symptoms. They were all women with an average age of 36.7. The most recurrent painful area was the right mandibular dermatome of the trigeminal nerve in patients with neuropathic pain symptoms.Conclusion: The prevalence of symptoms of neuropathic pain was 20% in patients referred for painful temporomandibular disorders. Dentists should evaluate neuropathic symptoms to provide a proper management of the condition.

Neuropathic Pain Components in Patients with Cancer: Prevalence, Treatment, and Interference with Daily Activities.

Pain and neuropathic symptoms impact quality of life of patients with cancer. To obtain more insight in the prevalence, severity, and treatment of neuropathic symptoms in patients with cancer and their interference with daily activities, we conducted a cross-sectional study at the outpatient clinic of a Dutch university hospital. A cross-sectional study among outpatients with cancer. To identify pain, its intensity, quality, and interference with daily activities, the Brief Pain Inventory (BPI) was used. Neuropathic symptoms were identified with the Douleur Neuropathique (DN4) interview and pain characteristics with the McGill Pain Questionnaire (MPQ). Pain medication and adjuvant analgesics were also collected with a prestructured questionnaire. Descriptives, chi-squared tests, t-tests, and a logistic regression analysis were conducted. 892 patients completed the questionnaires. Twenty-three percent (n=204) reported moderate to severe pain, and 19% (n=170) scored positive on neuropathic symptoms (DN4≥3). Particularly in patients with a rating on a numeric rating scale (NRS)<5, existence of neuropathic symptoms significantly increased interference with daily activities. Of patients with neuropathic symptoms, 8% received adjuvant pain treatment. Receiving curative treatment, using a systemic drug with neurotoxicity, having had an operation, and having had a lymph node dissection independently contributed to having neuropathic symptoms. This study shows that over 40% of the patients with moderate to severe pain also have neuropathic symptoms, causing increased interference with daily activities. Most of these patients do not receive adjuvant analgesics. There is a need to improve management of neuropathic symptoms in patients with cancer.

Neuropathic Symptoms and Their Risk Factors in Medical Oncology Outpatients With Colorectal vs. Breast, Lung, or Prostate Cancer: Results From a Prospective Multicenter Study

ContextFew studies have examined the prevalence and severity of treatment-induced neuropathic symptoms in patients across different cancer types. ObjectivesThis study aimed to report the prevalence of numbness/tingling (N/T) and neuropathic pain in patients with colorectal cancer (CRC) vs. other cancers, describe the prevalence of moderate-to-severe N/T by specific clinical variables, and examine factors associated with the presence of these symptoms. MethodsA total of 3106 outpatients with colorectal (n = 718), breast (n = 1544), lung (n = 524), or prostate (n = 320) cancer were enrolled at any point in their treatment. Assessments were conducted at the initial visit and 28–35 days later. Patients reported pain and N/T; clinicians reported mechanism of pain and ranked the top three symptoms causing difficulties. ResultsModerate-to-severe N/T was higher in patients with CRC relative to other cancer types (25.8% vs. 17.1%, P < 0.001); 25% vs. 10.5% of clinicians rated N/T as a top three symptom for patients with CRC relative to other cancers (P < 0.001). The prevalence of neuropathic pain was comparable between patients with CRC and other cancers (P = 0.654). Patients with CRC, longer duration of cancer, prior therapy, on current therapy, older patients, and patients of black race experienced worse N/T. ConclusionPatients with CRC experience significantly higher rates of N/T but comparable neuropathic pain, relative to patients with other cancers. Awareness of the prevalence and severity of neuropathic symptoms and their associated risk factors in this patient population is critical for both clinicians and patients.

Does cognitive functioning predict chronic pain? Results from a prospective surgical cohort

It is well established that chronic pain impairs cognition, particularly memory, attention and mental flexibility. Overlaps have been found between the brain regions involved in pain modulation and cognition, including in particular the prefrontal cortex and the anterior cingulate cortex, which are involved in executive function, attention and memory. However, whether cognitive function may predict chronic pain has not been investigated. We addressed this question in surgical patients, because such patients can be followed prospectively and may have no pain before surgery. In this prospective longitudinal study, we investigated the links between executive function, visual memory and attention, as assessed by clinical measurements and the development of chronic pain, its severity and neuropathic symptoms (based on the 'Douleur Neuropathique 4' questionnaire), 6 and 12 months after surgery (total knee arthroplasty for osteoarthritis or breast surgery for cancer). Neuropsychological tests included the Trail-Making Test A and B, and the Rey-Osterrieth Complex Figure copy and immediate recall, which assess cognitive flexibility, visuospatial processing and visual memory. Anxiety, depression and coping strategies were also evaluated. In total, we investigated 189 patients before surgery: 96% were re-evaluated at 6 months, and 88% at 12 months. Multivariate logistic regression (stepwise selection) for the total group of patients indicated that the presence of clinical meaningful pain at 6 and 12 months (pain intensity ≥ 3/10) was predicted by poorer cognitive performance in the Trail Making Test B (P = 0.0009 and 0.02 for pain at 6 and 12 months, respectively), Rey-Osterrieth Complex Figure copy (P = 0.015 and 0.006 for pain at 6 and 12 months, respectively) and recall (P = 0.016 for pain at 12 months), independently of affective variables. Linear regression analyses indicated that impaired scores on these tests predicted pain intensity (P < 0.01) and neuropathic symptoms in patients with pain (P < 0.05), although the strength of the association was less robust for neuropathic symptoms. These results were not affected by the type of surgery or presurgical pain, similar findings being obtained specifically for patients who initially had no pain. In conclusion, these findings support, for the first time, the notion that premorbid limited cognitive flexibility and memory capacities may be linked to the mechanisms of pain chronicity and probably also to its neuropathic quality. This may imply that patients with deficits in executive functioning or memory because of cerebral conditions have a greater risk of pain chronicity after a painful event.

Peripheral Neuropathy in Patients With Colorectal Cancer Receiving Oxaliplatin

Neuropathic side effects are commonly reported in patients receiving oxaliplatin, but little is known about the characteristics of peripheral neuropathy in this patient population. The purpose of this descriptive study was to explore the prevalence of neuropathic symptoms in patients with colorectal cancer receiving oxaliplatin as well as to explore symptom severity, distress, frequency, and neuropathic interference with activities. Thirty-three patients receiving oxaliplatin at two outpatient facilities completed the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool. Data were analyzed using descriptive statistics. Cold sensitivity, tingling in the hands, and numbness in the hands were the most prevalent neuropathic symptoms, and cold sensitivity, nerve pain, and trouble with balance were the most severe symptoms. Trouble with balance, muscle or joint aches, and neuropathic pain were the most distressing symptoms, and numbness in the fingers and hands and in the toes and feet were the most frequent symptoms. Patients reported that neuropathic symptoms interfered with numerous activities. Oncology nurses can use this information to help educate patients and families about potential side effects of oxaliplatin and to coordinate the care of patients with peripheral neuropathy using a symptom-focused, multidisciplinary approach.

Neuropathy in Diabetes

Neuropathic symptoms in patients with diabetes occur commonly and are most often a consequence of the diabetes. Up to 10% of patients with diabetes and neuropathy have an etiology other than diabetes as a cause of their nerve dysfunction. Herein we present a case of vasculitic neuropathy initially misdiagnosed as diabetic neuropathy that led to separate amputations of two toes. This case emphasizes the importance of considering alternative, potentially treatable, causes of peripheral neuropathy in patients with diabetes.

Efficacy of lamotrigine in the management of chemotherapy‐induced peripheral neuropathy

Lamotrigine, an antiepileptic agent, has been reported as being effective in reducing symptoms of neuropathy associated with various etiologies. Based on such data, a multicenter double-blind, placebo-controlled, randomized trial was conducted to evaluate the effect of lamotrigine on pain and other neuropathic symptoms due to chemotherapy-induced peripheral neuropathy (CIPN). Patients with symptomatic CIPN with symptom scores of either 1) >3 on a 0-10 Numerical Rating Scale (NRS) or 2) >1 on the 0-3 the Eastern Cooperative Oncology Group (ECOG) neuropathy scale (ENS) were eligible (higher numbers corresponding to greater severity of symptoms in both scales). Patients were randomly assigned to receive lamotrigine (target dose of 300 mg/day) or placebo for 10 weeks. Endpoints were measured biweekly. In all, 131 patients were enrolled. Both groups were well matched at baseline. Over the 10-week period of the trial, the average pain scores (NRS) for the lamotrigine and placebo arms declined in both arms, with no statistically significant difference noted between the changes in the 2 groups (0.3 and 0.5 unit reduction from baseline, respectively; P=.56). Similarly, decreases in the ENS with therapy were not statistically different (0.4 and 0.3, respectively; P=.3). Changes in other subjective symptom scales were also not found to be statistically different between the 2 groups. Toxicities were mild and similar in each group. The results suggest that lamotrigine is not effective for relieving neuropathic symptoms in patients because of CIPN.

Natural killer cells in patients with Guillain-Barré syndrome

We studied natural killer (NK) cell activity and NK cell number in peripheral blood of 20 patients with Guillain-Barré syndrome (GBS). NK cell activity obtained within 7 days after onset of neuropathic symptoms in patients with GBS was significantly decreased compared with that in 20 control subjects. NK cell activity was not well correlated with disease severity. After plasmapheresis, NK cell activity recovered to the normal range. Two-color flow cytometry showed that the NK cell subsets studied were quantitatively similar in GBS patients and controls.