Exercise for people with peripheral neuropathy.

PubMed

White, C M; Pritchard, J; Turner-Stokes, L

2004-10-18

Peripheral neuropathies are a wide range of diseases affecting the peripheral nerves. Demyelination or axonal degeneration gives rise to a variety of symptoms including reduced or altered sensation, pain, muscle weakness and fatigue. Secondary disability arises and this may result in adjustments to psychological and social function. Exercise therapy, with a view to developing strength and stamina, forms part of the treatment for people with peripheral neuropathy, particularly in the later stages of recovery from acute neuropathy and in chronic neuropathies. The primary objective was to examine the effect of exercise therapy on functional ability in the treatment of people with peripheral neuropathy. In addition, secondary outcomes of muscle strength, endurance, broader measures of health and well being, as well as unfavourable outcomes were examined. We searched the Cochrane Neuromuscular Disease Group register (July 2002 and updated February 2004) and MEDLINE (from January 1966 to June 2004), EMBASE (from January 1980 to June 2004), CINAHL (from January 1982 to July 2002) and LILACS (from January 1982 to July 2002) electronic databases. Bibliographies of all selected randomised controlled trials were checked and authors contacted to identify additional published or unpublished data. Any randomised or quasi-randomised controlled trial comparing the effect of exercise therapy with no exercise therapy or drugs or an alternative non-drug treatment on functional ability (or disability) in people with peripheral neuropathy at least eight weeks after randomisation was included. Two reviewers independently selected eligible studies, rated the methodological quality and extracted data. Only one trial fully met the inclusion criteria. An additional two trials assessed outcomes less than eight weeks after randomisation and were also included. Methodological quality was poor for several criteria in each study. Data used in the three studies could not be pooled due to

Treatment of human immunodeficiency virus-related peripheral neuropathy with Scrambler Therapy: a case report.

PubMed

Smith, Thomas J; Auwaerter, Paul; Knowlton, Amy; Saylor, Deanna; McArthur, Justin

2017-02-01

Peripheral neuropathy is one of the most common neurological complications of HIV infection with a 30-60% lifetime prevalence. Newer HIV drugs cause less peripheral neuropathy, but patients are now living long enough to develop concomitant diabetes-related, vascular-related, and chemotherapy-related neuropathy so it continues as a major debilitating issue. Recent national CDC guidelines have stressed the importance of non-opioid therapies, especially in this population that may have had drug abuse problems. We treated a 52-year-old man who had severe disabling classic peripheral neuropathy since 1998 with Scrambler Therapy (Calmare), an FDA-cleared peripheral non-invasive neuromodulation device. His pain rapidly improved, as did his motor and sensory function, with just four 45-min treatments, and he was able to come off opioids for the first time in years. When his pain returned six months later, only two treatments were needed to resolve it. This represents the first published use of this novel, inexpensive, and non-invasive pain modality in HIV peripheral neuropathy, and should engender further trials.

Peripheral neuropathy in prediabetes and the metabolic syndrome.

PubMed

Stino, Amro M; Smith, Albert G

2017-09-01

Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with diabetes develop neuropathy, and diabetic peripheral neuropathy (DPN) is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. Most patients with non-diabetic neuropathy have cryptogenic sensory peripheral neuropathy (CSPN). A growing body of literature links prediabetes, obesity and metabolic syndrome to the risk of both DPN and CSPN. This association might be particularly strong in type 2 diabetes patients. There are no effective medical treatments for CSPN or DPN, and aggressive glycemic control is an effective approach to neuropathy risk reduction only in type 1 diabetes. Several studies suggest lifestyle-based treatments that integrate dietary counseling with exercise might be a promising therapeutic approach to early DPN in type 2 diabetes and CSPN associated with prediabetes, obesity and metabolic syndrome. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

A Trial-Based Economic Evaluation Comparing Spinal Cord Stimulation With Best Medical Treatment in Painful Diabetic Peripheral Neuropathy.

PubMed

Slangen, Rachel; Faber, Catharina G; Schaper, Nicolaas C; Joosten, Elbert A; van Dongen, Robert T; Kessels, Alfons G; van Kleef, Maarten; Dirksen, Carmen D

2017-04-01

The objective was to perform an economic evaluation comparing spinal cord stimulation (SCS) in combination with best medical treatment (BMT) with BMT in painful diabetic peripheral neuropathy patients. Alongside a prospective 2-center randomized controlled trial, involving 36 painful diabetic peripheral neuropathy patients with severe lower limb pain not responding to conventional therapy, an economic evaluation was performed. Incremental cost-effectiveness ratios were based on: 1) societal costs and quality-adjusted life years (QALYs), and 2) direct health care costs and the number of successfully treated patients, respectively, both with a time horizon of 12 months. Bootstrap and secondary analyses were performed to address uncertainty. Total societal cost amounted to €26,539.18 versus €5,313.45 per patient in the SCS and BMT group, respectively. QALYs were .58 versus .36 and the number of successfully treated patients was 55% versus 7% for the SCS and BMT group, respectively. This resulted in incremental cost-effectiveness ratios of €94,159.56 per QALY and €34,518.85 per successfully treated patient, respectively. Bootstrap analyses showed that the probability of SCS being cost-effective ranges from 0 to 46% with willingness to pay threshold values ranging between €20,000 and €80,000 for a QALY. Secondary analyses showed that cost-effectiveness of SCS became more favorable after correcting for baseline cost imbalance between the 2 groups, extending the depreciation period of SCS material to 4 years, and extrapolation of the data up to 4 years. Although SCS was considerably more effective compared with BMT, the substantial initial investment that is required resulted in SCS not being cost-effective in the short term. Cost-effectiveness results were sensitive to baseline cost imbalances between the groups and the depreciation period of the SCS material. Painful diabetic peripheral neuropathy is a common complication of diabetes mellitus and the

Challenges Evaluating Chemotherapy-Induced Peripheral Neuropathy in Childhood Cancer Survivors.

PubMed

Mohrmann, Caroline; Armer, Jane; Hayashi, Robert J

Children treated for cancer are exposed to a variety of chemotherapeutic agents with known toxicity to the peripheral nervous system. The side effect of peripheral neuropathy can cause changes in sensation, function, and even cause pain. Although peripheral neuropathy is recognized by pediatric oncology nurses as an important and significant side effect, measuring neuropathy can be quite complex for clinical care and research efforts. With more children surviving a cancer diagnosis today, this issue is increasingly important for childhood cancer survivors. This article has reviewed existing literature examining peripheral neuropathy in childhood cancer survivors with particular interest paid to measurement tools available and needs for future research. It is important for nurses to choose appropriate measures for clinical care and research methods in order to have an impact on patients experiencing this condition.

Objective evaluation of chemotherapy-induced peripheral neuropathy using quantitative pain measurement system (Pain Vision®), a pilot study.

PubMed

Sato, Junya; Mori, Megumi; Nihei, Satoru; Takeuchi, Satoshi; Kashiwaba, Masahiro; Kudo, Kenzo

2017-01-01

In an evaluation of chemotherapy-induced peripheral neuropathy (CIPN), objectivity may be poor because the evaluation is determined by the patient's subjective assessment. In such cases, management of neuropathy may be delayed and CIPN symptoms may become severe. In this pilot study, we attempted an objective evaluation of CIPN using a quantitative pain measurement system (Pain Vision ® ). The subjects were patients with gynecologic cancer who underwent chemotherapy using taxane and platinum drugs. The grade of the peripheral sensory nerve disorder was based on the Common Terminology Criteria for Adverse Events (CTC-AE) ver. 4.0 and was evaluated before the initiation of therapy and up to six chemotherapy cycles. A symptom scale assessed by the patients using a peripheral neuropathy questionnaire (PNQ) was also evaluated. Simultaneously during these evaluations, graded electric current was applied from the probe to a fingertip and measured both the lowest perceptible current and lowest current perceived as pain by Pain Vision ® . From these values, the pain degree was calculated from the following formula: (pain perception current value - lowest perceptible current value) ÷ lowest perceptible current value × 100. We compared the pain degrees by Pain Vision ® during CIPN development with the value obtained before chemotherapy initiation. Forty-one patients were enrolled. In the evaluation by a medical professional, 28 (64.3%) patients developed CIPN during 2.5 ± 1.1 chemotherapy cycles (mean ± standard deviation). The pain degree by Pain Vision ® at grade 1 and 2 CIPN development according to the evaluation (CTC-AE) was significantly decreased compared to that before chemotherapy initiation (126.0 ± 114.5 vs. 69.8 ± 46.8, p  = 0.001, and 126.0 ± 114.5 vs. 32.8 ± 32.6, p  = 0.004). Changes in the pain degree by Pain Vision ® were also found during scale B and C, D CIPN development in the patient evaluation (PNQ) (115.9 ± 112.4 vs. 70

Peripheral neuropathy in HIV: an analysis of evidence-based approaches.

PubMed

Nicholas, Patrice K; Corless, Inge B; Evans, Linda A

2014-01-01

Peripheral neuropathy is a common and vexing symptom for people living with HIV infection (PLWH). Neuropathy occurs in several different syndromes and is identified in the literature as distal sensory polyneuropathy or distal sensory peripheral neuropathy. More recently, the HIV literature has focused on the syndrome as painful HIV-associated sensory neuropathy, addressing the symptom rather than the underlying pathophysiology. Assessment of neuropathy in PLWH is critical and must be incorporated into nursing practice for each visit. Neuropathy has been attributed to the direct effects of HIV, exposure to antiretroviral medications (particularly the nucleoside reverse transcriptase inhibitors), advanced immune suppression, and comorbid tuberculosis infection and exposure to antituberculosis medications. Evidence supports the importance of addressing neuropathy in PLWH with pharmacologic treatment regimens and complementary/alternative approaches. This paper examines the pathophysiology, evidence, and approaches to managing peripheral neuropathy. A case study has been included to illustrate a patient's experience with neuropathy symptoms. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Central or Peripheral Delivery of an Adenosine A1 Receptor Agonist Improves Mechanical Allodynia in a Mouse Model of Painful Diabetic Neuropathy

PubMed Central

Katz, N. K.; Ryals, J. M.; Wright, D. E.

2014-01-01

Diabetic peripheral neuropathy is a common complication of diabetes mellitus, and a significant proportion of individuals suffer debilitating pain that significantly affects their quality of life. Unfortunately, symptomatic treatment options have limited efficacy, and often carry significant risk of systemic adverse effects. Activation of the adenosine A1 receptor (A1R) by the analgesic small molecule adenosine has been shown to have antinociceptive benefits in models of inflammatory and neuropathic pain. The current study used a mouse model of painful diabetic neuropathy to determine the effect of diabetes on endogenous adenosine production, and if central or peripheral delivery of adenosine receptor agonists could alleviate signs of mechanical allodynia in diabetic mice. Diabetes was induced using streptozocin in male A/J mice. Mechanical withdrawal thresholds were measured weekly to characterize neuropathy phenotype. Hydrolysis of AMP into adenosine by ectonucleotidases was determined in the dorsal root ganglia (DRG) and spinal cord at 8-weeks post-induction of diabetes. AMP, adenosine and the specific A1R agonist, N6-cyclopentyladenosine (CPA), were administered both centrally (intrathecal) and peripherally (intraplantar) to determine the effect of activation of adenosine receptors on mechanical allodynia in diabetic mice. Eight weeks post-induction, diabetic mice displayed significantly decreased hydrolysis of extracellular AMP in the DRG; at this same time, diabetic mice displayed significantly decreased mechanical withdrawal thresholds compared to nondiabetic controls. Central delivery AMP, adenosine and CPA significantly improved mechanical withdrawal thresholds in diabetic mice. Surprisingly, peripheral delivery of CPA also improved mechanical allodynia in diabetic mice. This study provides new evidence that diabetes significantly affects endogenous AMP hydrolysis, suggesting that altered adenosine production could contribute to the development of painful

Skin autofluorescence and peripheral neuropathy four years later in type 1 diabetes.

PubMed

Rajaobelina, K; Farges, B; Nov, S; Maury, E; Cephise-Velayoudom, F L; Gin, H; Helmer, C; Rigalleau, V

2017-02-01

Advanced glycation end products (AGEs) are involved in diabetes complications. We aimed to investigate whether the accumulation of AGEs measured by skin autofluorescence (sAF) was associated with signs of diabetic peripheral neuropathy and to sensitivity, pain, motor and autonomic function 4 years later in patients with type 1 diabetes. At baseline, 188 patients (age 51 years, diabetes duration 22 years) underwent skin autofluorescence measurement using the AGE Reader. Four years later, signs of diabetic peripheral neuropathy were defined as the presence of neuropathic pain and/or feet sensory loss or foot ulceration. Neurological tests were systematically performed: vibration perception threshold by neuroesthesiometry, neuropathic pain by the Douleur Neuropathique en 4 Questions score, muscle strength by dynamometry and electrochemical skin conductance. Multivariate analyses were adjusted by age, sex, height, body mass index, tobacco, HbA 1c , diabetes duration, estimated glomerular filtration rate and albumin excretion rate. At the 4-year follow-up, 13.8% of patients had signs of diabetic peripheral neuropathy. The baseline sAF was higher in those with signs of diabetic peripheral neuropathy (2.5 ± 0.7 vs 2.1 ± 0.5 arbitrary units (AU), p < 0.0005). In the multivariate analysis, a 1 SD higher skin autofluorescence at baseline was associated with an increased risk of signs of neuropathy (OR = 2.68, p = 0.01). All of the neurological tests were significantly altered in the highest quartile of the baseline sAF (>2.4 AU) compared with the lowest quartiles after multivariate adjustment. This non-invasive measurement of skin autofluorescence may have a value for diabetic peripheral neuropathy in type 1 diabetes and a potential clinical utility for detection of diabetic peripheral neuropathy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Peripheral Neuropathy: Symptoms and Signs

MedlinePlus

... Utah Research News Make a Difference Symptoms of Peripheral Neuropathy Print This Page Peripheral Neuropathy symptoms usually start ... more slowly over many years. The symptoms of peripheral neuropathy often include: A sensation of wearing an invisible “ ...

CONTENT VALIDITY OF SYMPTOM-BASED MEASURES FOR DIABETIC, CHEMOTHERAPY, AND HIV PERIPHERAL NEUROPATHY

PubMed Central

GEWANDTER, JENNIFER S.; BURKE, LAURIE; CAVALETTI, GUIDO; DWORKIN, ROBERT H.; GIBBONS, CHRISTOPHER; GOVER, TONY D.; HERRMANN, DAVID N.; MCARTHUR, JUSTIN C.; MCDERMOTT, MICHAEL P.; RAPPAPORT, BOB A.; REEVE, BRYCE B.; RUSSELL, JAMES W.; SMITH, A. GORDON; SMITH, SHANNON M.; TURK, DENNIS C.; VINIK, AARON I.; FREEMAN, ROY

2017-01-01

Introduction No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures. Methods This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy. Results Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included. Conclusions Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. PMID:27447116

Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Areti, Aparna; Komirishetty, Prashanth; Kumar, Ash

Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheralmore » neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic

Chemotherapy-Induced Peripheral Neuropathy: A Current Review

PubMed Central

Staff, Nathan P.; Grisold, Anna; Grisold, Wolfgang; Windebank, Anthony J.

2017-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. Approximately 30–40% of patients treated with neurotoxic chemotherapy will develop CIPN and there is considerable variability in its severity between patients. It is often sensory-predominant with pain and can lead to long-term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents. PMID:28486769

Effectiveness of gabapentin pharmacotherapy in chemotherapy-induced peripheral neuropathy.

PubMed

Magnowska, Magdalena; Iżycka, Natalia; Kapoła-Czyż, Joanna; Romała, Anna; Lorek, Jakub; Spaczyński, Marek; Nowak-Markwitz, Ewa

2018-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common chemotherapy side effect, but its prevention and treatment remains a challenge. Neurotoxicity may lead to dose limitation or even treatment discontinuation, and therefore potentially affect the efficacy of anticancer treatment and long term outcomes. The practice to administer gabapentin for neuropathy may be applicable, but is limited by insufficient studies. The aim of our study was to assess the presence of chemotherapy-induced peripheral neuropathy in ovarian cancer patients treated with first-line paclitaxel and carboplatin chemotherapy and evaluate the effectiveness of gabapentin in treatment of this condition. 61 ovarian cancer patients treated with first line chemotherapy were included in the study. The first phase of the study was to assess neurological condition of each patient by: neuropathy symptoms scale, McGill's scale, neurological deficit and quality of life, during the chemotherapy. In the second phase of the study we evaluated the response to gabapentin treatment in a group of patients who developed neuropathy. 78.7% of the patients developed chemotherapy related neuropathy. During the course of chemotherapy these patients experienced significant exacerbation of neuropathy symptoms (p < 0.0001), neuropathic pain (p < 0.0001), neurologic deficit (p < 0.0012) and worsening of quality of life (p < 0.0002). Patients who were qualified to undergo the gabapentin treatment observed improvement in symptoms (p < 0.027), pain (p < 0.027) and neurologic deficit (p < 0.019). Quality of life did not change significantly after gabapentin treatment (p < 0.128). Chemotherapy substantially deteriorates the neurologic condition of the patients and the quality of life. Paclitaxel and carboplatin treated patients may benefit from gabapentin therapy in chemotherapy-induced peripheral neuropathy.

Content validity of symptom-based measures for diabetic, chemotherapy, and HIV peripheral neuropathy.

PubMed

Gewandter, Jennifer S; Burke, Laurie; Cavaletti, Guido; Dworkin, Robert H; Gibbons, Christopher; Gover, Tony D; Herrmann, David N; Mcarthur, Justin C; McDermott, Michael P; Rappaport, Bob A; Reeve, Bryce B; Russell, James W; Smith, A Gordon; Smith, Shannon M; Turk, Dennis C; Vinik, Aaron I; Freeman, Roy

2017-03-01

No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures. This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy. Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included. Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. Muscle Nerve 55: 366-372, 2017. © 2016 Wiley Periodicals, Inc.

Protective Effect of a Mitochondria-Targeted Peptide against the Development of Chemotherapy-Induced Peripheral Neuropathy in Mice.

PubMed

Toyama, Satoshi; Shimoyama, Naohito; Szeto, Hazel H; Schiller, Peter W; Shimoyama, Megumi

2018-04-18

Several chemotherapeutic agents used for cancer treatment induce dose-limiting peripheral neuropathy that compromises patients' quality of life and limits cancer treatment. Recently, mitochondrial dysfunction has been shown to be involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is a mitochondria-targeted peptide that promotes mitochondrial respiration and restores mitochondrial bioenergetics. In the present study, we examined the protective effect of SS-20 against the development of chemotherapy-induced peripheral neuropathy utilizing a murine model of peripheral neuropathy induced by oxaliplatin, a first-line chemotherapy agent for colon cancer. Weekly administrations of oxaliplatin induced peripheral neuropathy as demonstrated by the development of neuropathic pain and loss of intraepidermal nerve fibers in the hind paw. Continuous administration of SS-20 protected against the development of oxaliplatin-induced neuropathic pain and mitigated the loss of intraepidermal nerve fibers to normal levels. Our findings suggest that SS-20 may be a drug candidate for the prevention of chemotherapy-induced peripheral neuropathy.

Approach to Peripheral Neuropathy for the Primary Care Clinician.

PubMed

Doughty, Christopher T; Seyedsadjadi, Reza

2018-02-02

Peripheral neuropathy is commonly encountered in the primary care setting and is associated with significant morbidity, including neuropathic pain, falls, and disability. The clinical presentation of neuropathy is diverse, with possible symptoms including weakness, sensory abnormalities, and autonomic dysfunction. Accordingly, the primary care clinician must be comfortable using the neurologic examination-including the assessment of motor function, multiple sensory modalities, and deep tendon reflexes-to recognize and characterize neuropathy. Although the causes of peripheral neuropathy are numerous and diverse, careful review of the medical and family history coupled with limited, select laboratory testing can often efficiently lead to an etiologic diagnosis. This review offers an approach for evaluating suspected neuropathy in the primary care setting. It will describe the most common causes, suggest an evidence-based workup to aid in diagnosis, and highlight recent evidence that allows for selection of symptomatic treatment of patients with neuropathy. Copyright © 2018 Elsevier Inc. All rights reserved.

Cold therapy to prevent paclitaxel-induced peripheral neuropathy.

PubMed

Griffiths, Claire; Kwon, Nancy; Beaumont, Jennifer L; Paice, Judith A

2018-04-21

This case-control study was designed to assess the efficacy of cryotherapy to prevent paclitaxel-induced painful peripheral neuropathy in women with breast cancer. Participants served as their own paired control, with randomization of the cooled glove/sock to either the dominant or the non-dominant hand/foot, worn for 15 min prior to, during, and 15 min after completion of the paclitaxel infusion. Outcome measures included the Neuropathic Pain Symptom Inventory, the Brief Pain Inventory, and quantitative sensory testing. Data were measured at each of six time points-baseline, post-treatment (approximately 2 weeks after the last paclitaxel infusion), and at the first, fifth, ninth, and final weekly paclitaxel treatments. Of 29 randomized participants, 20 (69%) received at least one cryotherapy treatment, and 11 (38%) received all four cryotherapy treatments. Ten (34%) participants could not tolerate the cryotherapy, and six (21%) declined further participation at some point during the trial. Only seven participants (24%) were available for the final post-chemotherapy QST and questionnaires. There were no significant differences in measures of neuropathy or pain between treated and untreated hands or feet. Strategies to prevent painful peripheral neuropathy are urgently needed. In this current trial, dropout due to discomfort precluded adequate power to fully understand the potential benefits of cryotherapy. Much more research is needed to discover safe and effective preventive strategies that can be easily implemented within busy infusion centers.

Peripheral neuropathy in liver cirrhosis.

PubMed

Kharbanda, Parampreet S; Prabhakar, Sudesh; Chawla, Yogesh K; Das, Chandi P; Syal, Puneet

2003-08-01

Neuropathy in association with chronic liver disease, including cirrhosis, is recognized; however, there are differences in the incidence and type of neuropathy reported. The causal relationship of liver disease to neuropathy has been questioned. This study was designed to evaluate the incidence and character of peripheral neuropathy in patients with liver cirrhosis. The effect of alcohol consumption, severity of liver disease and encephalopathy on the incidence and severity of neuropathy were also studied. Patients having an identifiable cause of peripheral neuropathy, except alcohol, were excluded from the study. Patients with evidence of vitamin B12 deficiency or diabetes were also excluded from the study. In this study, 33 patients with liver cirrhosis were evaluated clinically and electrophysiologically to detect any evidence of peripheral neuropathy. Nerve conduction studies were performed in the upper and lower limbs using surface electrodes. These patients also underwent a detailed clinical examination. Clinical signs of peripheral neuropathy were found in seven (21%) patients. Nerve conduction studies were abnormal in 24 (73%) patients. The pattern of involvement was predominantly of an axonal sensory motor polyneuropathy. Neuropathy was found both in patients with alcohol-related and non-alcohol-related cirrhosis. The presence of encephalopathy did not have a significant bearing on the incidence and severity of neuropathy. The neuropathy was also not significantly related to the severity of liver disease. The present study reveals that a significant number of patients with liver cirrhosis show evidence of peripheral neuropathy, which is present regardless of the etiology of cirrhosis, and is subclinical in a majority of these patients. The cause of neuropathy was probably the liver disease itself, as the incidence and severity of neuropathy in the alcohol-related cirrhosis, although higher, was not significantly different from the neuropathy in patients

Evaluation of Peripheral Neuropathy of Unknown Origin in an Outpatient Foot and Ankle Practice.

PubMed

Klein, Sandra E; Chu, Jennifer; McCormick, Jeremy J; Johnson, Jeffrey E

2015-09-01

The foot and ankle surgeon can see peripheral neuropathy in the treatment of foot and ankle conditions. The purpose of this study was (1) to evaluate the demographics and presenting complaints of patients diagnosed with idiopathic peripheral neuropathy during an examination by a foot and ankle surgeon and (2) to identify the type and frequency of subsequent diagnosis of medical causes of neuropathy. This was a retrospective study of patients diagnosed with idiopathic peripheral neuropathy in our practice between January 1997 and December 2008. Ninety-five patients were identified, and demographic data, presenting complaints, and medical comorbidities were extracted from the medical record. Examination findings of decreased sensation to Semmes Weinstein 5.07 monofilament testing were documented, and electromyogram and nerve conduction study results were reviewed when available. Laboratory values were noted, as were neurologic evaluations performed to diagnose medical conditions associated with peripheral neuropathy. The most common presentation was foot pain, in 36 patients (38%). Ninety-one patients had Semmes Weinstein 5.07 monofilament testing, with loss of protective sensation reported in 75 of the 91 tested (82%). Only 30 of the 95 patients had electromyogram and nerve conduction study results available, with a test positive for peripheral neuropathy in 20 of the 30 tested. Thirty-two patients were evaluated by a neurologist. A specific cause was identified in 12 of the 32 seen by a neurologist. Of the total group of 95 patients, 31 patients (33%) were diagnosed with a condition that may be associated with peripheral neuropathy. Thirty-three percent of the patients presenting to our clinic and given a diagnosis of idiopathic peripheral neuropathy were ultimately diagnosed with a medical cause of neuropathy-most commonly, diabetes. For those patients with idiopathic neuropathy, a spectrum of disease was encountered, including pain, ulcer, infection, and Charcot

Burn-related peripheral neuropathy: A systematic review.

PubMed

Tu, Yiji; Lineaweaver, William C; Zheng, Xianyou; Chen, Zenggan; Mullins, Fred; Zhang, Feng

2017-06-01

Peripheral neuropathy is the most frequent disabling neuromuscular complication of burns. However, the insidious and progressive onset of burn neuropathy makes it often undiagnosed or overlooked. In our study, we reviewed the current studies on the burn-related peripheral neuropathy to summarize the morbidity, mechanism, detecting method and management of peripheral neuropathy in burn patients. Of the 1533 burn patients included in our study, 98 cases (6.39%) were presented with peripheral neuropathy. Thermal and electrical burns were the most common etiologies. Surgical procedures, especially nerve decompression, showed good effect on functional recovery of both acute and delayed peripheral neuropathy in burn patients. It is noteworthy that, for early detection and prevention of peripheral neuropathy, electrodiagnostic examinations should be performed on burn patients independent of symptoms. Still, the underlying mechanisms of burn-related peripheral neuropathy remain to be clarified. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy

PubMed Central

Marshall, Andrew G.; Lee-Kubli, Corinne; Azmi, Shazli; Zhang, Michael; Ferdousi, Maryam; Mixcoatl-Zecuatl, Teresa; Petropoulos, Ioannis N.; Ponirakis, Georgios; Fineman, Mark S.; Fadavi, Hassan; Frizzi, Katie; Tavakoli, Mitra; Jolivalt, Corinne G.; Boulton, Andrew J.M.; Efron, Nathan; Calcutt, Nigel A.

2017-01-01

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine. PMID:28202580

The use of complementary and alternative medicines by patients with peripheral neuropathy.

PubMed

Brunelli, Brian; Gorson, Kenneth C

2004-03-15

Complementary and alternative medicine (CAM) therapies have become increasingly popular and are used regularly by patients with chronic neurological disorders. The prevalence and characteristics of CAM use by patients with peripheral neuropathy is unknown. We performed a prospective, questionnaire-based study to determine the prevalence and patterns of use of CAM therapies in 180 consecutive outpatients with peripheral neuropathy. The use of CAM was reported by 77 patients (43%) with neuropathy. The most frequent were megavitamins (35%), magnets (30%), acupuncture (30%), herbal remedies (22%), and chiropractic manipulation (21%); 37 (48%) tried more than one form of alternative treatment. Seventeen respondents (27%) thought their neuropathy symptoms improved with these approaches. Those who used CAM were slightly younger (mean age 62 vs. 65 years, p = 0.05) and more often college educated (39% vs. 24%, p = 0.03) compared to CAM nonusers. They also more often reported burning neuropathic pain (62% vs. 44%, p = 0.01). Patients with diabetic neuropathy used CAM more frequently than others (p = 0.03). The most common reason for using CAM was inadequate pain control (32%). Almost half of patients did not consult a physician before starting CAM. We conclude that there is a high prevalence of CAM use in our patients with neuropathy, and one-quarter reported that their symptoms improved. CAM users were better educated than nonusers, but most did not discuss CAM treatments with their physician. Neuropathic pain was substantially more common in CAM users, and lack of pain control was the most common reason for CAM use.

Peripheral neuropathy in HIV: prevalence and risk factors

PubMed Central

Evans, Scott R.; Ellis, Ronald J.; Chen, Huichao; Yeh, Tzu-min; Lee, Anthony J.; Schifitto, Giovanni; Wu, Kunling; Bosch, Ronald J.; McArthur, Justin C.; Simpson, David M.; Clifford, David B.

2011-01-01

Objectives To estimate neuropathic sign/symptom rates with initiation of combination antiretroviral therapy (cART) in HIV-infected ART-naive patients, and to investigate risk factors for: peripheral neuropathy and symptomatic peripheral neuropathy (SPN), recovery from peripheral neuropathy/SPN after neurotoxic ART (nART) discontinuation, and the absence of peripheral neuropathy/SPN while on nART. Design AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trial participants who initiated cART in randomized trials for ART-naive patients were annually screened for symptoms/signs of peripheral neuropathy. ART use and disease characteristics were collected longitudinally. Methods Peripheral neuropathy was defined as at least mild loss of vibration sensation in both great toes or absent/hypoactive ankle reflexes bilaterally. SPN was defined as peripheral neuropathy and bilateral symptoms. Generalized estimating equation logistic regression was used to estimate associations. Results Two thousand, one hundred and forty-one participants were followed from January 2000 to June 2007. Rates of peripheral neuropathy/SPN at 3 years were 32.1/8.6% despite 87.1% with HIV-1RNA 400 copies/ml or less and 70.3% with CD4 greater than 350 cells/µl. Associations with higher odds of peripheral neuropathy included older patient age and current nART use. Associations with higher odds of SPN included older patient age, nART use, and history of diabetes mellitus. Associations with lower odds of recovery after nART discontinuation included older patient age. Associations with higher odds of peripheral neuropathy while on nART included older patient age and current protease inhibitor use. Associations with higher odds of SPN while on nART included older patient age, history of diabetes, taller height, and protease inhibitor use. Conclusion Signs of peripheral neuropathy remain despite virologic/immunologic control but frequently occurs without symptoms. Aging is a risk factor for

The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy

PubMed Central

2013-01-01

Background Oxaliplatin, the third-generation platinum compound, has evolved as one of the most important therapeutic agents in colorectal cancer chemotherapy. The main limiting factor in oxaliplatin treatment is painful neuropathy that is difficult to treat. This side effect has been studied for several years, but its full mechanism is still inconclusive, and effective treatment does not exist. Data suggest that oxaliplatin’s initial neurotoxic effect is peripheral and oxidative stress-dependent. A spinal target is also suggested in its mechanism of action. The flavonoids rutin and quercetin have been described as cell-protecting agents because of their antioxidant, antinociceptive, and anti-inflammatory actions. We proposed a preventive effect of these agents on oxaliplatin-induced painful peripheral neuropathy based on their antioxidant properties. Methods Oxaliplatin (1 mg/kg, i.v.) was injected in male Swiss mice, twice a week (total of nine injections). The development of sensory alterations, such as thermal and mechanical allodynia, was evaluated using the tail immersion test in cold water (10°C) and the von Frey test. Rutin and quercetin (25-100 mg/kg, i.p.) were injected 30 min before each oxaliplatin injection. The animals’ spinal cords were removed for histopathological and immunohistochemical evaluation and malondialdehyde assay. Results Oxaliplatin significantly increased thermal and mechanical nociceptive response, effects prevented by quercetin and rutin at all doses. Fos immunostaining in the dorsal horn of the spinal cord confirmed these results. The oxidative stress assays mainly showed that oxaliplatin induced peroxidation in the spinal cord and that rutin and quercetin decreased this effect. The flavonoids also decreased inducible nitric oxide synthase and nitrotyrosine immunostaining in the dorsal horn of the spinal cord. These results suggest that nitric oxide and peroxynitrite are also involved in the neurotoxic effect of oxaliplatin

Hyperacute peripheral neuropathy is a predictor of oxaliplatin-induced persistent peripheral neuropathy.

PubMed

Tanishima, Hiroyuki; Tominaga, Toshiji; Kimura, Masamichi; Maeda, Tsunehiro; Shirai, Yasutsugu; Horiuchi, Tetsuya

2017-05-01

Chronic peripheral neuropathy is a major adverse response to oxaliplatin-containing chemotherapy regimens, but there are no established risk factors pertaining to it. We investigated the efficacy of hyperacute peripheral neuropathy (HAPN) as a predictor of oxaliplatin-induced persistent peripheral neuropathy (PPN). Forty-seven cases of stage III colorectal cancer who received adjuvant chemotherapy with oxaliplatin after curative surgery between January 2010 and August 2014 were retrospectively reviewed. HAPN was defined as acute peripheral neuropathy (APN) occurring on day 1 (≤24 h after oxaliplatin infusion) of the first cycle. PPN was defined as neuropathy lasting >1 year after oxaliplatin discontinuation. The average total dose of oxaliplatin was 625.8 mg/m 2 , and the average relative dose intensity was 66.7%. Twenty-two of the 47 patients (46.8%) had PPN and 13 (27.7%) had HAPN. Male sex, treatment for neuropathy, HAPN, and APN were significantly more frequent in patients with PPN (p = 0.013, 0.02, <0.001, and 0.023, respectively). There was no significant difference in the total oxaliplatin dose between patients with and without PPN (p = 0.061). Multivariate analyses revealed total dose of oxaliplatin and HAPN as independent predictors of PPN [p = 0.015; odds ratio (OR) = 1.005, 95% confidence interval (CI), 1.001-1.009 and p = 0.001; OR = 75.307, 5.3-1070.123, respectively]. The total dose of oxaliplatin was relatively lower in patients with HAPN than that in those without HAPN in the PPN-positive group (not significant, p = 0.068). HAPN was found to be a predictor of oxaliplatin-induced PPN.

The Pain in Neuropathy Study (PiNS): a cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy

PubMed Central

Themistocleous, Andreas C.; Ramirez, Juan D.; Shillo, Pallai R.; Lees, Jonathan G.; Selvarajah, Dinesh; Orengo, Christine; Tesfaye, Solomon; Rice, Andrew S.C.; Bennett, David L.H.

2016-01-01

Abstract Disabling neuropathic pain (NeuP) is a common sequel of diabetic peripheral neuropathy (DPN). We aimed to characterise the sensory phenotype of patients with and without NeuP, assess screening tools for NeuP, and relate DPN severity to NeuP. The Pain in Neuropathy Study (PiNS) is an observational cross-sectional multicentre study. A total of 191 patients with DPN underwent neurological examination, quantitative sensory testing, nerve conduction studies, and skin biopsy for intraepidermal nerve fibre density assessment. A set of questionnaires assessed the presence of pain, pain intensity, pain distribution, and the psychological and functional impact of pain. Patients were divided according to the presence of DPN, and thereafter according to the presence and severity of NeuP. The DN4 questionnaire demonstrated excellent sensitivity (88%) and specificity (93%) in screening for NeuP. There was a positive correlation between greater neuropathy severity (r = 0.39, P < 0.01), higher HbA1c (r = 0.21, P < 0.01), and the presence (and severity) of NeuP. Diabetic peripheral neuropathy sensory phenotype is characterised by hyposensitivity to applied stimuli that was more marked in the moderate/severe NeuP group than in the mild NeuP or no NeuP groups. Brush-evoked allodynia was present in only those with NeuP (15%); the paradoxical heat sensation did not discriminate between those with (40%) and without (41.3%) NeuP. The “irritable nociceptor” subgroup could only be applied to a minority of patients (6.3%) with NeuP. This study provides a firm basis to rationalise further phenotyping of painful DPN, for instance, stratification of patients with DPN for analgesic drug trials. PMID:27088890

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

PubMed

Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

2017-08-17

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m 2 . Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

A highly successful and novel model for treatment of chronic painful diabetic peripheral neuropathy.

PubMed

Pfeifer, M A; Ross, D R; Schrage, J P; Gelber, D A; Schumer, M P; Crain, G M; Markwell, S J; Jung, S

1993-08-01

peripheral neuropathy. It uniquely bases the treatment algorithm on the types and sources of the pain.

Investigation of depression in Greek patients with diabetic peripheral neuropathy.

PubMed

Rekleiti, Maria; Sarafis, Pavlos; Saridi, Maria; Toska, Aikaterini; Melos, Chrysovaladis; Souliotis, Kyriakos; Tsironi, Maria

2013-06-16

Considerable studies directly connect the complications in diabetic patients, and especially peripheral neuropathy, with the emergence of depression. Neuropathetic pain may deteriorate the general health status of the diabetic patient and glycaemic regulation. The purpose of this study was to investigate the appearance and degree of diabetic peripheral neuropathy and its correlation with depression, with other parameters of the disease and also duration. 57 diabetic patients participated with diagnosed diabetic peripheral neuropathy (male n=27, female n= 30, mean of age 72.7±6.35 years). The first part of Michigan Neuropathy Screening Instrument and the Zung Depression Rating Scale were used as tools for our study. Data was analysed with the SPSS 18.0 statistic program. 57.9% of the patients were overweight, 35.1% were obese and only 7% were within normal weight range. The BMI findings between the two genders indicate that male participants are more often obese than females. Women surpassed men in the category of overweight patients (p < 0.05). The score based on MNSI was high and between 3 to 12 (mean average of 8.19±2.60 with 8 as intermediate rate). Almost 60% of patients had severe neuropathy, only 2 were found with mild symptoms and the rest had moderate neuropathtic symptoms, based on the score summary from the questionnaire. Investigating in detail the relation of diabetic neuropathy and depression, it derives that a high degree of diabetic neuropathy is related with high score of depression [F(3.160)=9.821, p=0.001]. Moderate and severe neuropathy was found with almost the same levels of depression. The correlation between diabetic neuropathy and depression is confirmed, while a very high depression rate was found in patients with severe neuropathy. The issue needs further study by using common instruments to obtain comparative results from the scientific community.

Diabetic peripheral neuropathy, is it an autoimmune disease?

PubMed

Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread

2015-11-01

Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (p<0.001). The odds of positive values of ANA in the neuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved.

Uridine monophosphate, folic acid and vitamin B12 in patients with symptomatic peripheral entrapment neuropathies.

PubMed

Negrão, Luis; Nunes, Paula

2016-01-01

Carpal tunnel syndrome is the most common type of peripheral entrapment neuropathy. We performed an exploratory, open-label, multicenter, observational study of 48 patients with peripheral entrapment neuropathy. Patients received a daily capsule of uridine monophosphate, folic acid + vitamin B12 for 2 months and were evaluated using the Pain DETECT questionnaire. The global score for pain decreased from 17.3 ± 5.9 at baseline to 10.3 ± 6.1 at the final evaluation (p < 0.001). Concomitant analgesic and anti-inflammatory treatment was stopped or the dose reduced in 77.4% of patients. Uridine monophosphate + folic acid + vitamin B12 reduced total pain score, intensity and characterization of pain and associated symptoms. These results should be tested in a well-designed, adequately powered randomized controlled trial.

Unipedal stance testing in the assessment of peripheral neuropathy.

PubMed

Hurvitz, E A; Richardson, J K; Werner, R A

2001-02-01

To define further the relation between unipedal stance testing and peripheral neuropathy. Prospective cohort. Electroneuromyography laboratory of a Veterans Affairs medical center and a university hospital. Ninety-two patients referred for lower extremity electrodiagnostic studies. A standardized history and physical examination designed to detect peripheral neuropathy, 3 trials of unipedal stance, and electrodiagnostic studies. Peripheral neuropathy was identified by electrodiagnostic testing in 32%. These subjects had a significantly shorter (p <.001) unipedal stance time (15.7s, longest of 3 trials) than the patients without peripheral neuropathy (37.1s). Abnormal unipedal stance time (<45s) identified peripheral neuropathy with a sensitivity of 83% and a specificity of 71%, whereas a normal unipedal stance time had a negative predictive value of 90%. Abnormal unipedal stance time was associated with an increased risk of having peripheral neuropathy on univariate analysis (odds ratio = 8.8, 95% confidence interval = 2.5--31), and was the only significant predictor of peripheral neuropathy in the regression model. Aspects of the neurologic examination did not add to the regression model compared with abnormal unipedal stance time. Unipedal stance testing is useful in the clinical setting both to identify and to exclude the presence of peripheral neuropathy.

Paclitaxel-induced peripheral neuropathy increases substance P release in rat spinal cord.

PubMed

Chiba, Terumasa; Oka, Yusuke; Kambe, Toshie; Koizumi, Naoya; Abe, Kenji; Kawakami, Kazuyoshi; Utsunomiya, Iku; Taguchi, Kyoji

2016-01-05

Peripheral neuropathy is a common adverse effect of paclitaxel treatment. The major dose-limiting side effect of paclitaxel is peripheral sensory neuropathy, which is characterized by painful paresthesia of the hands and feet. To analyze the contribution of substance P to the development of paclitaxel-induced mechanical hyperalgesia, substance P expression in the superficial layers of the rat spinal dorsal horn was analyzed after paclitaxel treatment. Behavioral assessment using the von Frey test and the paw thermal test showed that intraperitoneal administration of 2 and 4mg/kg paclitaxel induced mechanical allodynia/hyperalgesia and thermal hyperalgesia 7 and 14 days after treatment. Immunohistochemistry showed that paclitaxel (4mg/kg) treatment significantly increased substance P expression (37.6±3.7% on day 7, 43.6±4.6% on day 14) in the superficial layers of the spinal dorsal horn, whereas calcitonin gene-related peptide (CGRP) expression was unchanged. Moreover, paclitaxel (2 and 4mg/kg) treatment significantly increased substance P release in the spinal cord on day 14. These results suggest that paclitaxel treatment increases release of substance P, but not CGRP in the superficial layers of the spinal dorsal horn and may contribute to paclitaxel-induced painful peripheral neuropathy. Copyright © 2015 Elsevier B.V. All rights reserved.

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Starobova, Hana; Vetter, Irina

2017-01-01

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches. PMID:28620280

Rationale and design of a randomized double-blind clinical trial in breast cancer: dextromethorphan in chemotherapy-induced peripheral neuropathy.

PubMed

Martin, Elodie; Morel, Véronique; Joly, Dominique; Villatte, Christine; Delage, Noémie; Dubray, Claude; Pereira, Bruno; Pickering, Gisèle

2015-03-01

Anti-cancer chemotherapy often induces peripheral neuropathy and consequent cognitive and quality of life impairment. Guidelines recommend antiepileptics or antidepressants but their efficacy is limited.Dextromethorphan, a N-methyl-D-aspartate receptor antagonist, has shown its efficacy in painful diabetic neuropathy and in post-operative pain but has not been studied in chemotherapy-induced peripheral neuropathy. This clinical trial evaluates the effect of dextromethorphan on pain, cognition and quality of life in patients who suffer from neuropathic pain induced by chemotherapy for breast cancer. It also assesses the impact of dextromethorphan genetic polymorphism on analgesia. This trial is a randomized, placebo-controlled, double-blind clinical study in two parallel groups (NCT02271893). It includes 40 breast cancer patients suffering from chemotherapy-induced peripheral neuropathy. They are randomly allocated to dextromethorphan (maximal dose 90 mg/day) or placebo for 4 weeks. The primary endpoint is pain intensity measured after 4 weeks of treatment on a (0-10) Numeric Pain Rating Scale. Secondary outcomes include assessment of neuropathic pain, cognitive function, anxiety/depression, sleep and quality of life. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α=0.05. Considering the poor efficacy of available drugs in chemotherapy-induced neuropathic pain, dextromethorphan may be a valuable therapeutic option. Pharmacogenetics may provide predictive factors of dextromethorphan response in patients suffering from breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Painful Traumatic Trigeminal Neuropathy.

PubMed

Rafael, Benoliel; Sorin, Teich; Eli, Eliav

2016-08-01

This article discusses neuropathic pain of traumatic origin affecting the trigeminal nerve. This syndrome has been termed painful traumatic trigeminal neuropathy by the International Headache Society and replaces atypical odontalgia, deafferentation pain, traumatic neuropathy, and phantom toothache. The discussion emphasizes the diagnosis and the early and late management of injuries to the trigeminal nerve and subsequent painful conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Peripheral Neuropathy

MedlinePlus

... of days, weeks, or years. They can be acute or chronic. In acute neuropathies such as Guillain-Barré syndrome (in which ... that warns of impending heart attack or other acute conditions. Loss of pain sensation is a particularly ...

Treatment of peripheral neuropathies.

PubMed Central

Hallett, M; Tandon, D; Berardelli, A

1985-01-01

There are three general approaches to treatment of peripheral neuropathy. First, an attempt should be made to reverse the pathophysiological process if its nature can be elucidated. Second, nerve metabolism can be stimulated and regeneration encouraged. Third, even if the neuropathy itself cannot be improved, symptomatic therapy can be employed. This review outlines the options available for each approach. PMID:3003254

Peripheral Neuropathy – Clinical and Electrophysiological Considerations

PubMed Central

Chung, Tae; Prasad, Kalpana; Lloyd, Thomas E.

2013-01-01

This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography (MRN) has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field MRN may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

POEMS Syndrome Diagnosed 10 Years after Disabling Peripheral Neuropathy.

PubMed

Nguyen, Viet H

2011-01-01

Peripheral neuropathy is characterized as a generalized, relatively homogeneous process affecting many peripheral nerves and predominantly affecting distal nerves. The epidemiology of peripheral neuropathy is limited since the disease presents with varying etiology, pathology, and severity. Toxic, inflammatory, hereditary, and infectious factors can cause damage to the peripheral nerves resulting in peripheral neuropathy. Peripheral neuropathy is most commonly caused by diabetes, alcohol, HIV infection, and malignancy. We report a case of a 42-year-old female with 10-year history of progressively worsening peripheral neuropathy, hypothyroidism, and skin changes who presents with dyspnea secondary to recurrent pleural and pericardial effusions. Prior to her arrival, her peripheral neuropathy was believed to be secondary to chronic demyelinating inflammatory polyneuropathy (CDIP) given elevated protein in the cerebral spinal fluid (CSF) which was treated with intravenous immunoglobulin (IVIG) and corticosteroids. Unfortunately, her peripheral neuropathy did not have any improvement. Incidentally, patient was found to have splenomegaly and papilledema on physical exam. Serum protein electrophoresis showed a monoclonal pattern of IgA lambda. Patient met the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. An underlying diagnosis of POEMS syndrome should be considered in patients with chronic debilitating neuropathy and an elevated protein in the CSF.

POEMS Syndrome Diagnosed 10 Years after Disabling Peripheral Neuropathy

PubMed Central

Nguyen, Viet H.

2011-01-01

Peripheral neuropathy is characterized as a generalized, relatively homogeneous process affecting many peripheral nerves and predominantly affecting distal nerves. The epidemiology of peripheral neuropathy is limited since the disease presents with varying etiology, pathology, and severity. Toxic, inflammatory, hereditary, and infectious factors can cause damage to the peripheral nerves resulting in peripheral neuropathy. Peripheral neuropathy is most commonly caused by diabetes, alcohol, HIV infection, and malignancy. We report a case of a 42-year-old female with 10-year history of progressively worsening peripheral neuropathy, hypothyroidism, and skin changes who presents with dyspnea secondary to recurrent pleural and pericardial effusions. Prior to her arrival, her peripheral neuropathy was believed to be secondary to chronic demyelinating inflammatory polyneuropathy (CDIP) given elevated protein in the cerebral spinal fluid (CSF) which was treated with intravenous immunoglobulin (IVIG) and corticosteroids. Unfortunately, her peripheral neuropathy did not have any improvement. Incidentally, patient was found to have splenomegaly and papilledema on physical exam. Serum protein electrophoresis showed a monoclonal pattern of IgA lambda. Patient met the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. An underlying diagnosis of POEMS syndrome should be considered in patients with chronic debilitating neuropathy and an elevated protein in the CSF. PMID:22013451

Usability and Acceptability of a Web-Based Program for Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Tofthagen, Cindy; Kip, Kevin E; Passmore, Denise; Loy, Ian; Berry, Donna L

2016-07-01

Chemotherapy-induced neuropathy is a painful and debilitating adverse effect of certain chemotherapy drugs. There have not been any patient-centered, easily accessible Web-based interventions to assist with self-management of chemotherapy-induced neuropathy. The aims of this study were to evaluate usability and acceptability and to estimate an effect size of a Web-based intervention for assessing and managing chemotherapy-induced neuropathy. Participants (N = 14) were instructed to complete the Creativity, Optimism, Planning, and Expert Information for Chemotherapy-Induced Peripheral Neuropathy program and provide verbal responses to the program. Participants completed the Chemotherapy Induced Peripheral Neuropathy Assessment Tool and Post-Study System Usability Questionnaire. Iterative changes were made to the COPE-CIPN. Participants were asked to provide feedback on the revised COPE-CIPN, repeat the Chemotherapy Induced Peripheral Neuropathy Assessment Tool, and evaluate acceptability using the Acceptability e-Scale. The COPE-CIPN demonstrated high usability (mean, 1.98 [SD, 1.12]) and acceptability (mean, 4.40 [SD, 0.52]). Comments indicated that the interface was easy to use, and the information was helpful. While neuropathy symptoms continued to increase in this group of patients receiving neurotoxic chemotherapy, there was a decrease in mean level of interference with activities from 53.71 to 39.29 over 3 to 4 months, which indicated a moderate effect (d = 0.39) size. The COPE-CIPN may be a useful intervention to support self-management of chemotherapy-induced neuropathy.

Symptomatic and Electrodiagnostic Features of Peripheral Neuropathy in Scleroderma.

PubMed

Paik, Julie J; Mammen, Andrew L; Wigley, Fredrick M; Shah, Ami A; Hummers, Laura K; Polydefkis, Michael

2016-08-01

To determine the prevalence of peripheral neuropathy in scleroderma. The prevalence of length-dependent peripheral neuropathy was rigorously assessed using signs and symptoms of neuropathy derived from the Total Neuropathy Score (TNS), and standardized nerve conduction study (NCS). All subjects underwent TNS and NCS. Those who were symptomatic or had NCS evidence of peripheral neuropathy underwent laboratory evaluation for secondary causes of neuropathy. A total of 130 subjects were approached for participation and 60 enrolled. Of the 60 subjects, 50 (83.3%) were female and 37 (61.7%) were of the limited cutaneous subtype. The mean ± SD age was 55 ± 11.1 years, and mean ± SD disease duration was 15.3 ± 10.1 years. A total of 17 of 60 (28%) had evidence of a peripheral neuropathy as defined by the presence of neuropathic symptoms on the TNS (12 of 60) and/or electrophysiologic evidence of neuropathy (5 subjects with neuropathic symptoms and 5 without neuropathic symptoms). Subjects with neuropathy were more likely to be male (60% versus 40%; P = 0.02), African American (41% versus 4.6%; P = 0.001), have diabetes mellitus (17.7% versus 0%; P = 0.02), have limited cutaneous scleroderma (82.3% versus 53.5%; P = 0.04), and have anti-U1 RNP antibodies (23.5% versus 0%; P = 0.009) than those without neuropathy. A potential nonscleroderma etiology for the peripheral neuropathy such as diabetes mellitus was found in 82.3% (14 of 17) of subjects with neuropathy. While symptoms or objective evidence of peripheral neuropathy are common among patients with scleroderma, the cause may often be attributed to comorbid nonscleroderma-related conditions. © 2016, American College of Rheumatology.

Alpha-1 adrenoceptor hyperresponsiveness in three neuropathic pain states: complex regional pain syndrome 1, diabetic peripheral neuropathic pain and central pain states following spinal cord injury.

PubMed

Teasell, Robert W; Arnold, J Malcolm O

2004-01-01

The pathophysiology of the pain associated with complex regional pain syndrome, spinal cord injury and diabetic peripheral neuropathy is not known. The pain of complex regional pain syndrome has often been attributed to abnormal sympathetic nervous system activity based on the presence of vasomotor instability and a frequently reported positive response, albeit a temporary response, to sympathetic blockade. In contrast, the pain below the level of spinal cord injury and diabetic peripheral neuropathy are generally seen as deafferentation phenomena. Each of these pain states has been associated with abnormal sympathetic nervous system function and increased peripheral alpha-1 adrenoceptor activity. This increased responsiveness may be a consequence of alpha-1 adrenoceptor postsynaptic hypersensitivity, or alpha-2 adrenoceptor presynaptic dysfunction with diminished noradrenaline reuptake, increased concentrations of noradrenaline in the synaptic cleft and increased stimulation of otherwise normal alpha-1 adrenoceptors. Plausible mechanisms based on animal research by which alpha-1 adrenoceptor hyperresponsiveness can lead to chronic neuropathic-like pain have been reported. This raises the intriguing possibility that sympathetic nervous system dysfunction may be an important factor in the generation of pain in many neuropathic pain states. Although results to date have been mixed, there may be a greater role for new drugs which target peripheral alpha-2 adrenoceptors (agonists) or alpha-1 adrenoceptors (antagonists).

Chinese herbal medicine for diabetic peripheral neuropathy.

PubMed

Chen, Wei; Zhang, Yin; Liu, Jian Ping

2011-06-15

Chinese herbal medicine is frequently used for treating diabetic peripheral neuropathy in China. Many controlled trials have been undertaken to investigate its efficacy. To assess the beneficial effects and harms of Chinese herbal medicine for people with diabetic peripheral neuropathy. We searched the Cochrane Neuromuscular Disease Group Specialized Register (15 June 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2010 in The Cochrane Library), MEDLINE (January 1966 to June 2010), EMBASE (January 1980 to June 2010), AMED (January 1985 to June 2010), Chinese Biomedical Database (CBM) (1979 to June 2010), Chinese National Knowledge Infrastructure Database (CNKI) (1979 to June 2010), and VIP Chinese Science and Technique Journals Database (1989 to June 2010). We searched for unpublished literature in the Chinese Conference Papers Database and Chinese Dissertation Database (from inception to March 2010). No language or publication restrictions were used. We included randomized controlled trials of Chinese herbal medicine (with a minimum of four weeks treatment duration) for people with diabetic peripheral neuropathy compared with placebo, no intervention, or conventional interventions. Trials of herbal medicine plus a conventional drug versus the drug alone were also included. Two authors independently extracted data and evaluated trial quality. We contacted study authors for additional information. The data analyses were carried out using Review Manager 5.1 (Cochrane software). Thirty-nine randomized trials involving 2890 participants were included. All trials were conducted and published in China. Thirty different herbal medicines were tested in these trials, including four single herbs (extracts from a single herb), eight traditional Chinese patent medicines, and 18 self-concocted Chinese herbal compound prescriptions. The trials reported on global symptom improvement (including improvement in numbness or pain) and changes in nerve

Peripheral neuropathy associated with mitochondrial disease in children.

PubMed

Menezes, Manoj P; Ouvrier, Robert A

2012-05-01

Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy.

PubMed

Iqbal, Zohaib; Azmi, Shazli; Yadav, Rahul; Ferdousi, Maryam; Kumar, Mohit; Cuthbertson, Daniel J; Lim, Jonathan; Malik, Rayaz A; Alam, Uazman

2018-06-01

Diabetic peripheral neuropathy (DPN) is the commonest cause of neuropathy worldwide, and its prevalence increases with the duration of diabetes. It affects approximately half of patients with diabetes. DPN is symmetric and predominantly sensory, starting distally and gradually spreading proximally in a glove-and-stocking distribution. It causes substantial morbidity and is associated with increased mortality. The unrelenting nature of pain in this condition can negatively affect a patient's sleep, mood, and functionality and result in a poor quality of life. The purpose of this review was to critically review the current literature on the diagnosis and treatment of DPN, with a focus on the treatment of neuropathic pain in DPN. A comprehensive literature review was undertaken, incorporating article searches in electronic databases (EMBASE, PubMed, OVID) and reference lists of relevant articles with the authors' expertise in DPN. This review considers seminal and novel research in epidemiology; diagnosis, especially in relation to novel surrogate end points; and the treatment of neuropathic pain in DPN. We also consider potential new pharmacotherapies for painful DPN. DPN is often misdiagnosed and inadequately treated. Other than improving glycemic control, there is no licensed pathogenetic treatment for diabetic neuropathy. Management of painful DPN remains challenging due to difficulties in personalizing therapy and ascertaining the best dosing strategy, choice of initial pharmacotherapy, consideration of combination therapy, and deciding on defining treatment for poor analgesic responders. Duloxetine and pregabalin remain first-line therapy for neuropathic pain in DPN in all 5 of the major published guidelines by the American Association of Clinical Endocrinologists, American Academy of Neurology, European Federation of Neurological Societies, National Institute of Clinical Excellence (United Kingdom), and the American Diabetes Association, and their use has been

Motor Nerve Conduction Velocity In Postmenopausal Women with Peripheral Neuropathy.

PubMed

Singh, Akanksha; Asif, Naiyer; Singh, Paras Nath; Hossain, Mohd Mobarak

2016-12-01

The post-menopausal phase is characterized by a decline in the serum oestrogen and progesterone levels. This phase is also associated with higher incidence of peripheral neuropathy. To explore the relationship between the peripheral motor nerve status and serum oestrogen and progesterone levels through assessment of Motor Nerve Conduction Velocity (MNCV) in post-menopausal women with peripheral neuropathy. This cross-sectional study was conducted at Jawaharlal Nehru Medical College during 2011-2013. The study included 30 post-menopausal women with peripheral neuropathy (age: 51.4±7.9) and 30 post-menopausal women without peripheral neuropathy (control) (age: 52.5±4.9). They were compared for MNCV in median, ulnar and common peroneal nerves and serum levels of oestrogen and progesterone estimated through enzyme immunoassays. To study the relationship between hormone levels and MNCV, a stepwise linear regression analysis was done. The post-menopausal women with peripheral neuropathy had significantly lower MNCV and serum oestrogen and progesterone levels as compared to control subjects. Stepwise linear regression analysis showed oestrogen with main effect on MNCV. The findings of the present study suggest that while the post-menopausal age group is at a greater risk of peripheral neuropathy, it is the decline in the serum estrogen levels which is critical in the development of peripheral neuropathy.

CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.

PubMed

Huang, Zhen-Zhen; Li, Dai; Liu, Cui-Cui; Cui, Yu; Zhu, He-Quan; Zhang, Wen-Wen; Li, Yong-Yong; Xin, Wen-Jun

2014-08-01

Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased cleaved caspase-3 expression, induced the loss of primary afferent terminal fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn, indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of macrophage in vitro study. Intrathecal or systemic injection of CX3CL1 neutralizing antibody blocked paclitaxel-induced macrophage recruitment and neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia. Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

Rare NaV1.7 variants associated with painful diabetic peripheral neuropathy

PubMed Central

Blesneac, Iulia; Themistocleous, Andreas C.; Fratter, Carl; Conrad, Linus J.; Ramirez, Juan D.; Cox, James J.; Tesfaye, Solomon; Shillo, Pallai R.; Rice, Andrew S.C.; Tucker, Stephen J.

2018-01-01

Abstract Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes. Almost half of the patients with DPN develop neuropathic pain (NeuP) for which current analgesic treatments are inadequate. Understanding the role of genetic variability in the development of painful DPN is needed for improved understanding of pain pathogenesis for better patient stratification in clinical trials and to target therapy more appropriately. Here, we examined the relationship between variants in the voltage-gated sodium channel NaV1.7 and NeuP in a deeply phenotyped cohort of patients with DPN. Although no rare variants were found in 78 participants with painless DPN, we identified 12 rare NaV1.7 variants in 10 (out of 111) study participants with painful DPN. Five of these variants had previously been described in the context of other NeuP disorders and 7 have not previously been linked to NeuP. Those patients with rare variants reported more severe pain and greater sensitivity to pressure stimuli on quantitative sensory testing. Electrophysiological characterization of 2 of the novel variants (M1852T and T1596I) demonstrated that gain of function changes as a consequence of markedly impaired channel fast inactivation. Using a structural model of NaV1.7, we were also able to provide further insight into the structural mechanisms underlying fast inactivation and the role of the C-terminal domain in this process. Our observations suggest that rare NaV1.7 variants contribute to the development NeuP in patients with DPN. Their identification should aid understanding of sensory phenotype, patient stratification, and help target treatments effectively. PMID:29176367

Treatment options in painful diabetic neuropathy.

PubMed

Nash, T P

1999-01-01

Diabetic neuropathy is common in patients with diabetes mellitus, and 7.5% of diabetics experience pain from diabetic neuropathy. Complications of diabetes mellitus are more common where control of the disease is not optimal. By improving the control of the disease, both the neuropathy and the pain it can produce may be improved. The pain of diabetic neuropathy can frequently be controlled using analgesics, antidepressants, anticonvulsants, topical capsaicin, and neuromodulation, either alone or in any combination.

Epidemiology of Peripheral Neuropathy: An Indian Perspective

PubMed Central

Trivedi, Sweety; Pandit, Alak; Ganguly, Goutam; Das, Shyamal Kumar

2017-01-01

Peripheral neuropathy (PN) is a common disorder and presents as diagnostic and therapeutic challenge to physicians and neurologists. In epidemiological studies from India from various regions the overall prevalence of PN varied from 5 to 2400 per 10,000 population in various community studies. India is composed of a multiethnic, multicultural population who are exposed to different adverse environmental factors such as arsenic and lead. Use of different chemotherapeutic agents with propensity to affect peripheral nerves, increasing methods of diagnosis of connective tissue disorders and use of immunomodulating drugs, growing aging population is expected to change the spectrum and burden of peripheral neuropathy in the community. The other important aspect of peripheral neuropathies is in terms of the geographical and occupational distribution especially of toxic neuropathies like arsenic which is common in eastern belt; lead, mercury and organo-phosphorous compounds where occupational exposures are major sources. Inflammatory neuropathies either due to vasculitis or G B Syndrome, chronic inflammatory polyradiculopathies are another major group of neuropathies which is increasing due to increase longevity of Indian subjects and immunological impairment, also adds to morbidity of the patients and are potentially treatable. Leprous neuropathy is common in India and although its frequency is significantly decreasing because of national control program yet pure neuritic form still remains a cause of concern and similar is the case with another infective cause like diptheric neurpathy. Thus this article is an attempt to cover major categories and also highlight the areas where further studies are needed. PMID:28904445

Animal Models of Peripheral Neuropathy Due to Environmental Toxicants

PubMed Central

Rao, Deepa B.; Jortner, Bernard S.; Sills, Robert C.

2014-01-01

Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy—namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves. PMID:24615445

Lipid-lowering drugs (statins) and peripheral neuropathy.

PubMed

Emad, Mohammadreza; Arjmand, Hosein; Farpour, Hamid Reza; Kardeh, Bahareh

2018-03-01

Peripheral neuropathy is a disorder with often unknown causes. Some drugs, including statins, are proposed to be among the causes of peripheral neuropathy. This study aimed at evaluating this condition by electrodiagnostic study among patients who had received statins. This case-control study was conducted in Shiraz, Iran in 2015, and included 39 patients aged 35-55 who had received statins for at least 6 months, and 39 healthy matched controls. Using electrodiagnosis, the sensory and motor wave features (amplitude, latency and nerve conduction velocity) of the peripheral nerves (Median, Ulnar, Tibial, Sural, and Peroneal) were evaluated among the subjects. Data were analyzed using SPSS software and p<0.05 was considered statistically significant. Regarding the occurrence of neuropathy, there were no significant differences in any of the definitions presented for peripheral neuropathy. However, the difference was close to significance for one definition [2 abnormalities in 2 nerves (p=0.055)]. Regarding mean values of the features, significant differences were observed in two features: amplitude of the peroneal motor nerve (p=0.048) and amplitude of the sural sensory nerve (p=0.036). Since statins are widely used, awareness regarding their side-effects would lead to better treatment. Even though no significant differences were found between the groups regarding the occurrence of peripheral neuropathy, there were significant differences in amplitudes of the sural sensory response and the peroneal motor response. This indicates the involvement of peripheral nerves. Therefore, we recommend that patients and physicians should be informed about the possible symptoms of this condition.

Peripheral Neuropathy Due to Vitamin Deficiency, Toxins, and Medications

PubMed Central

Staff, Nathan P.; Windebank, Anthony J.

2014-01-01

Purpose of Review: Peripheral neuropathies secondary to vitamin deficiencies, medications, or toxins are frequently considered but can be difficult to definitively diagnose. Accurate diagnosis is important since these conditions are often treatable and preventable. This article reviews the key features of different types of neuropathies caused by these etiologies and provides a comprehensive list of specific agents that must be kept in mind. Recent Findings: While most agents that cause peripheral neuropathy have been known for years, newly developed medications that cause peripheral neuropathy are discussed. Summary: Peripheral nerves are susceptible to damage by a wide array of toxins, medications, and vitamin deficiencies. It is important to consider these etiologies when approaching patients with a variety of neuropathic presentations; additionally, etiologic clues may be provided by other systemic symptoms. While length-dependent sensorimotor axonal peripheral neuropathy is the most common presentation, several examples present in a subacute severe fashion, mimicking Guillain-Barré syndrome. PMID:25299283

The clinical identification of peripheral neuropathy among older persons.

PubMed

Richardson, James K

2002-11-01

To identify simple clinical rules for the detection of a diffuse peripheral neuropathy among older outpatients. Observational, blinded, controlled study. A tertiary-care electrodiagnostic laboratory and biomechanics laboratory. One hundred research subjects, 68 with electrodiagnostic evidence of peripheral neuropathy, between the ages of 50 and 80 years. Not applicable. One examiner, unaware of the results of electrodiagnostic testing, evaluated Achilles' and patellar reflexes, Romberg testing, semiquantified vibration, and position sense at the toe and ankle in all subjects, and unipedal stance time and the Michigan Diabetes Neuropathy Score in a subset of subjects. Significant group differences were present in all clinical measures tested. Three signs, Achilles' reflex (absent despite facilitation), vibration (128Hz tuning fork perceived for <10s), and position sense (<8/10 1-cm trials) at the toe, were the best predictors of peripheral neuropathy on both univariate and logistic regression (pseudo R(2)=.744) analyses. The presence of 2 or 3 signs versus 0 or 1 sign identified peripheral neuropathy with sensitivity, specificity, and positive and negative predictive values of 94.1%, 84.4%, 92.8%, and 87.1%, respectively. Values were similar among subgroups of subjects with and without diabetes mellitus. When other clinicians applied the technique to 12 more subjects, excellent interrater reliability regarding the presence of peripheral neuropathy (kappa=.833) and good to excellent interrater reliability for each sign (kappa range,.667-1.00) were shown. Among older persons, the presence of 2 or 3 of the 3 clinical signs strongly suggested electrodiagnostic evidence of a peripheral neuropathy, regardless of etiology. Age-related decline in peripheral nerve function need not be a barrier to the clinical recognition of a diffuse peripheral neuropathy among older persons. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of

Quality assessment of online patient education resources for peripheral neuropathy.

PubMed

Hansberry, David R; Suresh, Ragha; Agarwal, Nitin; Heary, Robert F; Goldstein, Ira M

2013-03-01

Given its practicality, the internet is a primary resource for patients afflicted with diseases like peripheral neuropathy. Therefore, it is important that the readily available online resources on peripheral neuropathy are tailored to the general public, particularly concerning readability. Patient education resources were downloaded from the US National Library of Medicine, Mayo Clinic, National Institute of Neurological Disorders and Stroke, Neuropathy.org, GBS/CIDP Foundation International, Hereditary Neuropathy Foundation, Charcot-Marie-Tooth Association, Foundation for Peripheral Neuropathy, and Neuropathy Action Foundation websites. All patient education material related to peripheral neuropathy was evaluated for its level of readability using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level. The FRE scores averaged 43.4 with only the US National Library of Medicine scoring above 60 (76.5). The Flesch-Kincaid Grade Level scores averaged 11.0. All scores were above a seventh-grade level except the US National Library of Medicine, which had a score of a fifth-grade reading level. Most Americans may not fully benefit from patient education resources concerning peripheral neuropathy education on many of the websites. Only the US National Library of Medicine, which is written at a fifth-grade level, is likely to benefit the average American. © 2013 Peripheral Nerve Society.

Hepatitis C-related cryoglobulinemic neuropathy: potential role of oxcarbazepine for pain control.

PubMed

Moretti, Rita; Caruso, Paola; Dal Ben, Matteo; Gazzin, Silvia; Tiribelli, Claudio

2018-01-25

Peripheral neuropathy is one most common, limiting and invalidating neurological symptom in subjects with hepatitis C virus and mixed cryoglobulinemia. Notably, the medical therapy proposed to eradicate HCV, can frequently exacerbate the painful neuropathy. Therefore, neuropathy therapies are insufficient and inadequate, and comprise immunosuppressive drugs, such as steroid or cyclosporine, intravenous immunoglobulin or plasma exchange. These have shown variable success in case reports, with a presumably temporary effect, but with major side effects. We assessed the effects of oxcarbazepine treatment in 67 cases of cryoglobulinemia related neuropathy, who did not respond to either steroid or Gabapentin, or Pregabalin. Oxcarbazepine was chosen based on the promising preliminary results. Patients treated with Oxcarbazepine showed a rapid, discrete and persistent relief of polyneuropathic signs, without consistent side effects, and with a limited interaction with concomitant drugs. These data favor the use of oxcarbazepine as a useful tool in the management of neuropathic pain associated with Hepatitis-C cryoglobulin neuropathy.

Ambient geothermal hydrogen sulfide exposure and peripheral neuropathy

PubMed Central

Pope, Karl; So, Yuen T.; Crane, Julian; Bates, Michael N.

2017-01-01

The mechanism of toxicity of hydrogen sulfide (H2S) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether chronic exposure causes effects, including peripheral neuropathy, is yet unclear. The city of Rotorua, New Zealand, sits on an active geothermal field and the population has some of the highest measured ambient H2S exposures. A previous study in Rotorua provided evidence that H2S is associated with peripheral neuropathy. Using clinical methods, the present study sought to investigate and possibly confirm this association in the Rotorua population. The study population comprised 1,635 adult residents of Rotorua, aged 18–65. Collected data relevant to the peripheral neuropathy investigation included symptoms, ankle stretch reflex, vibration sensitivity, as measured by the timed-tuning fork test and a Bio-Thesiometer (Bio-Medical Instrument Co., Ohio), and light touch sensitivity measured by monofilaments. An exposure metric, estimating time-weighted H2S exposure across the last 30 years was used. Principal components analysis was used to combine data across the various indicators of possible peripheral neuropathy. The main data analysis used linear regression to examine associations between the peripheral nerve function indicators and H2S exposure. None of the peripheral nerve function indicators were associated with H2S exposure, providing no evidence that H2S exposure at levels found in Rotorua is a cause of peripheral neuropathy. The earlier association between H2S exposure and peripheral neuropathy diagnoses may be attributable to the ecological study design used. The possibility that H2S exposure misclassification could account for the lack of association found cannot be entirely excluded. PMID:28223159

Ambient geothermal hydrogen sulfide exposure and peripheral neuropathy.

PubMed

Pope, Karl; So, Yuen T; Crane, Julian; Bates, Michael N

2017-05-01

The mechanism of toxicity of hydrogen sulfide (H 2 S) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether chronic exposure causes effects, including peripheral neuropathy, is yet unclear. The city of Rotorua, New Zealand, sits on an active geothermal field and the population has some of the highest measured ambient H 2 S exposures. A previous study in Rotorua provided evidence that H 2 S is associated with peripheral neuropathy. Using clinical methods, the present study sought to investigate and possibly confirm this association in the Rotorua population. The study population comprised 1635 adult residents of Rotorua, aged 18-65. Collected data relevant to the peripheral neuropathy investigation included symptoms, ankle stretch reflex, vibration sensitivity, as measured by the timed-tuning fork test and a Bio-Thesiometer (Bio-Medical Instrument Co., Ohio), and light touch sensitivity measured by monofilaments. An exposure metric, estimating time-weighted H 2 S exposure across the last 30 years was used. Principal components analysis was used to combine data across the various indicators of possible peripheral neuropathy. The main data analysis used linear regression to examine associations between the peripheral nerve function indicators and H 2 S exposure. None of the peripheral nerve function indicators were associated with H 2 S exposure, providing no evidence that H 2 S exposure at levels found in Rotorua is a cause of peripheral neuropathy. The earlier association between H 2 S exposure and peripheral neuropathy diagnoses may be attributable to the ecological study design used. The possibility that H 2 S exposure misclassification could account for the lack of association found cannot be entirely excluded. Copyright © 2017 Elsevier B.V. All rights reserved.

Diabetes and obesity are the main metabolic drivers of peripheral neuropathy.

PubMed

Callaghan, Brian C; Gao, LeiLi; Li, Yufeng; Zhou, Xianghai; Reynolds, Evan; Banerjee, Mousumi; Pop-Busui, Rodica; Feldman, Eva L; Ji, Linong

2018-04-01

To determine the associations between individual metabolic syndrome (MetS) components and peripheral neuropathy in a large population-based cohort from Pinggu, China. A cross-sectional, randomly selected, population-based survey of participants from Pinggu, China was performed. Metabolic phenotyping and neuropathy outcomes were performed by trained personnel. Glycemic status was defined according to the American Diabetes Association criteria, and the MetS using modified consensus criteria (body mass index instead of waist circumference). The primary peripheral neuropathy outcome was the Michigan Neuropathy Screening Instrument (MNSI) examination. Secondary outcomes were the MNSI questionnaire and monofilament testing. Multivariable models were used to assess for associations between individual MetS components and peripheral neuropathy. Tree-based methods were used to construct a classifier for peripheral neuropathy using demographics and MetS components. The mean (SD) age of the 4002 participants was 51.6 (11.8) and 51.0% were male; 37.2% of the population had normoglycemia, 44.0% prediabetes, and 18.9% diabetes. The prevalence of peripheral neuropathy increased with worsening glycemic status (3.25% in normoglycemia, 6.29% in prediabetes, and 15.12% in diabetes, P < 0.0001). Diabetes (odds ratio [OR] 2.60, 95% CI 1.77-3.80) and weight (OR 1.09, 95% CI 1.02-1.18) were significantly associated with peripheral neuropathy. Age, diabetes, and weight were the primary splitters in the classification tree for peripheral neuropathy. Similar to previous studies, diabetes and obesity are the main metabolic drivers of peripheral neuropathy. The consistency of these results reinforces the urgent need for effective interventions that target these metabolic factors to prevent and/or treat peripheral neuropathy.

Acupuncture Treatment of Diabetic Peripheral Neuropathy in an American Indian Community.

PubMed

Bailey, Anne; Wingard, Deborah; Allison, Matthew; Summers, Priscilla; Calac, Daniel

2017-04-01

Diabetic peripheral neuropathy (DPN) develops in 30% of type 2 diabetes patients, increases the risk for foot ulcers and amputation, and is a significant source of disability and medical costs. Treatment remains challenging, propelling research to focus on therapeutic methods that aim to improve blood circulation or ameliorate oxidative stress that drives development of DPN. The aim of this study was to assess the effectiveness of acupuncture treatment for DPN symptoms and lower extremity arterial circulation in people with type 2 diabetes. Twenty-five patients seen at a Southern California Tribal Health Center who reported a threshold level of diabetic neuropathy symptoms in the lower extremities during the previous 4 weeks received acupuncture treatment once per week over a 10-week period between 2011 and 2013. The Neuropathy Total Symptom Scale (NTSS-6), Neuropathy Disability Score (NDS), and laser Doppler fluxmetry (LDF) were used for assessment at baseline and 10 weeks. A total of 19 of 25 study participants completed the study and reported a significant reduction in the NTSS symptoms of aching pain, burning pain, prickling sensation, numbness, and allodynia. Lancinating pain did not decrease significantly. LDF measures improved but not significantly. Acupuncture may effectively ameliorate selected DPN symptoms in these American Indian patients. Copyright © 2017 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.

Chinese herbal medicine for diabetic peripheral neuropathy.

PubMed

Chen, Wei; Zhang, Yin; Li, Xinxue; Yang, Guoyan; Liu, Jian Ping

2013-10-06

Chinese herbal medicine is frequently used for treating diabetic peripheral neuropathy in China. Many controlled trials have been undertaken to investigate its efficacy.This is an update of a Cochrane review that was first published in the year 2011. To assess the beneficial effects and harms of Chinese herbal medicine for people with diabetic peripheral neuropathy. On 14 May 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register CENTRAL (2012, Issue 4 in The Cochrane Library), MEDLINE (January 1966 to May 2012), EMBASE (January 1980 to May 2012), AMED (January 1985 to May 2012) and in October 2012, the Chinese Biomedical Database (CBM) (1979 to October 2012), Chinese National Knowledge Infrastructure Database (CNKI) (1979 to October 2012), and VIP Chinese Science and Technique Journals Database (1989 to October 2012). We searched for unpublished literature in the Chinese Conference Papers Database, and Chinese Dissertation Database (from inception to October 2012). There were no language or publication restrictions. We included randomised controlled trials of Chinese herbal medicine (with a minimum of four weeks treatment duration) for people with diabetic peripheral neuropathy compared with placebo, no intervention, or conventional interventions. Trials of herbal medicine plus a conventional drug versus the drug alone were also included. Two authors independently extracted data and evaluated trial quality. We contacted study authors for additional information. Forty-nine randomised trials involving 3639 participants were included. All trials were conducted and published in China. Thirty-eight different herbal medicines were tested in these trials, including four single herbs (extracts from a single herb), eight traditional Chinese patent medicines, and 26 self concocted Chinese herbal compound prescriptions. The trials reported on global symptom improvement (including improvement in numbness or pain) and changes in nerve conduction

Vitamin B supplementation for diabetic peripheral neuropathy.

PubMed

Jayabalan, Bhavani; Low, Lian Leng

2016-02-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. Copyright © Singapore Medical Association.

Vitamin B supplementation for diabetic peripheral neuropathy

PubMed Central

Jayabalan, Bhavani; Low, Lian Leng

2016-01-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. PMID:26892473

Sensory, psychological, and metabolic dysfunction in HIV-associated peripheral neuropathy: A cross-sectional deep profiling study

PubMed Central

Phillips, Tudor J.C.; Brown, Matthew; Ramirez, Juan D.; Perkins, James; Woldeamanuel, Yohannes W.; Williams, Amanda C. de C.; Orengo, Christine; Bennett, David L.H.; Bodi, Istvan; Cox, Sarah; Maier, Christoph; Krumova, Elena K.; Rice, Andrew S.C.

2014-01-01

HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of HIV infection and a major source of morbidity. A cross-sectional deep profiling study examining HIV-SN was conducted in people living with HIV in a high resource setting using a battery of measures which included the following: parameters of pain and sensory symptoms (7 day pain diary, Neuropathic Pain Symptom Inventory [NPSI] and Brief Pain Inventory [BPI]), sensory innervation (structured neurological examination, quantitative sensory testing [QST] and intraepidermal nerve fibre density [IENFD]), psychological state (Pain Anxiety Symptoms Scale-20 [PASS-20], Depression Anxiety and Positive Outlook Scale [DAPOS], and Pain Catastrophizing Scale [PCS], insomnia (Insomnia Severity Index [ISI]), and quality of life (Short Form (36) Health Survey [SF-36]). The diagnostic utility of the Brief Peripheral Neuropathy Screen (BPNS), Utah Early Neuropathy Scale (UENS), and Toronto Clinical Scoring System (TCSS) were evaluated. Thirty-six healthy volunteers and 66 HIV infected participants were recruited. A novel triumvirate case definition for HIV-SN was used that required 2 out of 3 of the following: 2 or more abnormal QST findings, reduced IENFD, and signs of a peripheral neuropathy on a structured neurological examination. Of those with HIV, 42% fulfilled the case definition for HIV-SN (n = 28), of whom 75% (n = 21) reported pain. The most frequent QST abnormalities in HIV-SN were loss of function in mechanical and vibration detection. Structured clinical examination was superior to QST or IENFD in HIV-SN diagnosis. HIV-SN participants had higher plasma triglyceride, concentrations depression, anxiety and catastrophizing scores, and prevalence of insomnia than HIV participants without HIV-SN. PMID:24973717

Association between pain severity and health care resource use, health status, productivity and related costs in painful diabetic peripheral neuropathy patients.

PubMed

DiBonaventura, Marco Dacosta; Cappelleri, Joseph C; Joshi, Ashish V

2011-05-01

Research has shown that painful diabetic peripheral neuropathy (pDPN) is associated with worse health outcomes. However, among pDPN patients, few studies have examined the relationship between the severity of pain and health outcomes. The current project included pDPN patients (N=1506) from the 2006, 2007, and 2008 waves of the National Health and Wellness Survey. Health status (Short Form [SF]-12), work productivity (Work Productivity and Activity Impairment questionnaire), and health care resource use in the past 6 months were compared among pDPN patients with mild, moderate, and severe pain, adjusting for demographics and clinical characteristics. More than half (51.2%) of the patients reported their pain as severe, 45.2% reported moderate pain, and 3.7% reported mild pain. Those with severe pain reported significantly lower levels of health status, higher levels of work and activity impairment, and higher levels of resource use relative to the other groups. Annual per-patient costs for those with severe pain were $12,856, $3927, and $16,783 for direct, indirect, and total costs, respectively. Both direct and total costs were significantly higher in this group relative to both mild and moderate pain patients. These results suggest that pain severity contributes substantially to the health outcomes of pDPN patients and that greater resources should be allocated to the management of patients with severe pain. Wiley Periodicals, Inc.

Emerging drugs for diabetic peripheral neuropathy and neuropathic pain.

PubMed

Papanas, Nikolaos; Ziegler, Dan

2016-12-01

Diabetic sensorimotor polyneuropathy (DSPN) is a common complication of diabetes. Areas covered: In this review, the authors discuss the emerging drugs for DSPN, which aim either at improving alleviation of neuropathic pain or addressing the putative mechanisms underlying diabetic neuropathy. Expert Opinion: Current treatment does not address the sensory deficits and pathogenesis underlying DSPN, so there is an unmet need for treatment options targeting the natural history of the condition. Some of these pathogenetic therapies have demonstrated clinically relevant improvements in neuropathic endpoints in recent randomised controlled trials. Since any effective analgesic monotherapy is known to induce a clinically meaningful response in only some 50% of the patients, there remains a substantial unmet need in patients with neuropathic pain. Advanced knowledge in the neurobiology of neuropathic pain and improved phenotypic profiling have led to a burst of research into novel pharmaceutical approaches. An array of promising molecular entities have reached the clinical stage of development, which should improve our therapeutic armamentarium in the fight against DSPN and neuropathic pain in the foreseeable future.

Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

PubMed

Addington, James; Freimer, Miriam

2016-01-01

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

Comparison of peripheral nerve blockade characteristics between non-diabetic patients and patients suffering from diabetic neuropathy: a prospective cohort study.

PubMed

Baeriswyl, M; Taffé, P; Kirkham, K R; Bathory, I; Rancati, V; Crevoisier, X; Cherix, S; Albrecht, E

2018-06-02

Animal data have demonstrated increased block duration after local anaesthetic injections in diabetic rat models. Whether the same is true in humans is currently undefined. We, therefore, undertook this prospective cohort study to test the hypothesis that type-2 diabetic patients suffering from diabetic peripheral neuropathy would have increased block duration after ultrasound-guided popliteal sciatic nerve block when compared with patients without neuropathy. Thirty-three type-2 diabetic patients with neuropathy and 23 non-diabetic control patients, scheduled for fore-foot surgery, were included prospectively. All patients received an ultrasound-guided popliteal sciatic nerve block with a 30 ml 1:1 mixture of lidocaine 1% and bupivacaine 0.5%. The primary outcome was time to first opioid request after block procedure. Secondary outcomes included the time to onset of sensory blockade, and pain score at rest on postoperative day 1 (numeric rating scale 0-10). These outcomes were analysed using an accelerated failure time regression model. Patients in the diabetic peripheral neuropathy group had significantly prolonged median (IQR [range]) time to first opioid request (diabetic peripheral neuropathy group 1440 (IQR 1140-1440 [180-1440]) min vs. control group 710 (IQR 420-1200 [150-1440] min, p = 0.0004). Diabetic peripheral neuropathy patients had a time ratio of 1.57 (95%CI 1.10-2.23, p < 0.01), experienced a 59% shorter time to onset of sensory blockade (median time ratio 0.41 (95%CI 0.28-0.59), p < 0.0001) and had lower median (IQR [range]) pain scores at rest on postoperative day 1 (diabetic peripheral neuropathy group 0 (IQR 0-1 [0-5]) vs. control group 3 (IQR 0-5 [0-9]), p = 0.001). In conclusion, after an ultrasound-guided popliteal sciatic nerve block, patients with diabetic peripheral neuropathy demonstrated reduced time to onset of sensory blockade, with increased time to first opioid request when compared with patients without neuropathy. © 2018 The

Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy

PubMed Central

Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka

2015-01-01

Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P < 0.05). We also tested whether there is an association between peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P < 0.05), with the strongest association being with motor neuropathy (P < 0.001). Our data from cells and from patients with breast cancer suggest that 1-deoxysphingolipids, the very-long-chain in particular, play a role as molecular intermediates of paclitaxel-induced peripheral neuropathy.—Kramer, R., Bielawski, J., Kistner-Griffin, E., Othman, A., Alecu, I., Ernst, D., Kornhauser, D., Hornemann, T., Spassieva, S. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy. PMID:26198449

Longitudinal patient-oriented outcomes in neuropathy

PubMed Central

Kerber, Kevin; Langa, Kenneth M.; Banerjee, Mousumi; Rodgers, Ann; McCammon, Ryan; Burke, James; Feldman, Eva

2015-01-01

Objective: To evaluate longitudinal patient-oriented outcomes in peripheral neuropathy over a 14-year time period including time before and after diagnosis. Methods: The 1996–2007 Health and Retirement Study (HRS)–Medicare Claims linked database identified incident peripheral neuropathy cases (ICD-9 codes) in patients ≥65 years. Using detailed demographic information from the HRS and Medicare claims, a propensity score method identified a matched control group without neuropathy. Patient-oriented outcomes, with an emphasis on self-reported falls, pain, and self-rated health (HRS interview), were determined before and after neuropathy diagnosis. Generalized estimating equations were used to assess differences in longitudinal outcomes between cases and controls. Results: We identified 953 peripheral neuropathy cases and 953 propensity-matched controls. The mean (SD) age was 77.4 (6.7) years for cases, 76.9 (6.6) years for controls, and 42.1% had diabetes. Differences were detected in falls 3.0 years before neuropathy diagnosis (case vs control; 32% vs 25%, p = 0.008), 5.0 years for pain (36% vs 27%, p = 0.002), and 5.0 years for good to excellent self-rated health (61% vs 74%, p < 0.0001). Over time, the proportion of fallers increased more rapidly in neuropathy cases compared to controls (p = 0.002), but no differences in pain (p = 0.08) or self-rated health (p = 0.9) were observed. Conclusions: In older persons, differences in falls, pain, and self-rated health can be detected 3–5 years prior to peripheral neuropathy diagnosis, but only falls deteriorates more rapidly over time in neuropathy cases compared to controls. Interventions to improve early peripheral neuropathy detection are needed, and future clinical trials should incorporate falls as a key patient-oriented outcome. PMID:26019191

Chemotherapy-Induced Peripheral Neuropathy in Pediatric Cancer Patients

PubMed Central

Groninger, Hunter

2014-01-01

Chemotherapy-induced peripheral neuropathies (CIPNs) are an increasingly common neuropathic and pain syndrome in adult and pediatric cancer patients and survivors [1–69]. However, symptoms associated with CIPNs are often undiagnosed, under-assessed, and communications problems between clinicians, family members, and patients have been observed [70–73]. Less is known about the prevalence and impact of CIPNs on pediatric cancer populations [70–71]. This article aims to provide a brief understanding of CIPNs in pediatric populations, and to review the evidence for both its prevention and treatment. PMID:25144779

Cutaneous manifestations of diabetic peripheral neuropathy.

PubMed

Dogiparthi, S N; Muralidhar, K; Seshadri, K G; Rangarajan, S

2017-01-01

There is a rise in number of people diagnosed with Diabetes Mellitus. The incidence is rising in modern Indian society because of Industrial development and drastically changing lifestyles. Diabetic neuropathies are microvascular disorders that are usually associated with the duration of Diabetes. Among the various forms, the most common is Diabetic Peripheral Neuropathy. The disease if neglected leads to chronic ulcer formation leading to amputations frequently. Hence the aim of this study is to document the early cutaneous changes and create an early awareness in the importance of controlling Diabetes. The study consisted of 205 patients with Type 2 DM. Participant's neuropathy status was determined based on Neuropathy Disability Score and Diabetic Neuropathy Symptom Score. Among the Skin changes documented, the common changes seen were: Peripheral hair loss in 185 (90.2%), Xerosis in 168 (82%), Anhydrosis in 162 (79%), Plantar Fissures in 136 (66.3%), Plantar Ulcer in 80 (39%), common nail changes documented were Onychomycosis in 165 (80.5%) and Onychauxis in 53 (25.8%) patients in relation to the occupation and duration of Diabetes mellitus. In conclusion, it is important to control glycemic levels in the all stages of Diabetes and institute foot care measures to prevent the complications of neuropathy.

[Peripheral neuropathy and blood-nerve barrier].

PubMed

Kanda, Takashi

2009-11-01

It is important to know the cellular properties of endoneurial microvascular endothelial cells (PnMECs) and microvascular pericytes which constitute blood-nerve barrier (BNB), since this barrier structure in the peripheral nervous system (PNS) may play pivotal pathophysiological roles in various disorders of the PNS including inflammatory neuropathies (i.e. Guillain-Barré syndrome), vasculitic neuropathies, hereditary neuropathies and diabetic neuropathy. However, in contrast to blood-brain barrier (BBB), very few studies have been directed to BNB and no adequate cell lines originating from BNB had been launched. In our laboratory, we successfully established human immortalized cell lines originating from BNB using temperature-sensitive SV40 large T antigen and the cellular properties of human cell lines are presented in this paper. Human PnMEC cell line showed high transendothelial electrical resistance and expressed tight junction components and various types of influx as well as efflux transporters that have been reported to function at BBB. Human pericyte cell line also possessed tight junction proteins except claudin-5 and secrete various cytokines and growth factors including bFGF, VEGF, GDNF, NGF, BDNF and angiopoietin-1. Co-culture with pericytes or pericyte-conditioned media strengthend barrier properties of PnMEC, suggesting that in the PNS, peripheral nerve pericytes support the BNB function and play the same role of astrocytes in the BBB. Future accumulation of the knowledge concerning the cellular properties of BNB-forming cells will open the door to novel therapeutic strategies for intractable peripheral neuropathies.

Electroacupuncture is not effective in chronic painful neuropathies.

PubMed

Penza, Paola; Bricchi, Monica; Scola, Amalia; Campanella, Angela; Lauria, Giuseppe

2011-12-01

  To investigate the analgesic efficacy of electroacupuncture (EA) in patients with chronic painful neuropathy.   Double-blind, placebo-controlled, cross-over study. Inclusion criteria were diagnosis of peripheral neuropathy, neuropathic pain (visual analog scale > 4) for at least 6 months, and stable analgesic medications for at least 3 months.   Sixteen patients were randomized into two arms to be treated with EA or pseudo-EA (placebo).   The protocol included 6 weeks of treatment, 12 weeks free of treatment, and then further 6 weeks of treatment. EA or pseudo-EA was performed weekly during each treatment period.   The primary outcome was the number of patients treated with EA achieving at least 50% of pain relief at the end of each treatment compared with pain intensity at baseline. Secondary outcomes were modification in patient's global impression of change, depression and anxiety, and quality of life.   Eleven patients were randomized to EA and five patients to pseudo-EA as the first treatment. Only one patient per group (EA and pseudo-EA) reported 50% of pain relief at the end of each treatment compared with pain intensity at baseline. Pain intensity did not differ between EA (5.7 ± 2.3 at baseline and 4.97 ± 3.23 after treatment) and pseudo-EA (4.9 ± 1.9 at baseline and 4.18 ± 2.69 after treatment). There was no difference between patients who received EA as the first treatment and patients initially treated with placebo. There was no change in the secondary outcomes.   Our results do not support the use of EA in this population of painful neuropathy patients. Further studies in larger groups of patients are warranted to confirm our observation. Wiley Periodicals, Inc.

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure

PubMed Central

Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A.; Vengamma, B.; Sivakumar, V.; Kolli, Satyarao

2017-01-01

Objective: To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Materials and Methods: Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. Results: The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure (n = 100) and severe renal failure patients (n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Conclusion: Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics. PMID:29204008

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure.

PubMed

Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A; Vengamma, B; Sivakumar, V; Kolli, Satyarao

2017-01-01

To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure ( n = 100) and severe renal failure patients ( n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics.

Small-fiber neuropathy and pain sensitization in survivors of pediatric acute lymphoblastic leukemia.

PubMed

Lieber, S; Blankenburg, M; Apel, K; Hirschfeld, G; Hernáiz Driever, P; Reindl, T

2018-05-01

Chemotherapy-induced Peripheral Neuropathy (CIPN) of large-fibers affects up to 20% of survivors of pediatric acute lymphoblastic leukemia (ALL). We aimed to describe small-fiber toxicity and pain sensitization in this group. In a cross-sectional, bicentric study we assessed 46 survivors of pediatric ALL (Mean age: 5.7 ± 3.5 years at diagnosis, median 2.5 years after therapy; males: 28). ≥6 years of age, ≥3 months after last administration of Vincristine, and cumulative dose of Vincristine 12 mg/m 2 . We used a reduced version of the Pediatric-modified Total Neuropathy Score (Ped-mTNS) as bedside test and Quantitative Sensory Testing (QST) for assessment of small- and large-fiber neuropathy as well as pain sensitization. We employed Nerve Conduction Studies (NCS) as the most accurate tool for detecting large-fiber neuropathy. Fifteen survivors (33%) had abnormal rPed-mTNS values (≥4 points) and 5 survivors (11%) reported pain. In QST, the survivor group showed significant (p < 0.001) inferior large-fiber function and pain sensitization when compared to healthy matched peers. We identified deficits of vibration in 33 (72%) and tactile hypoesthesia in 29 (63%), hyperalgesia to blunt pressure in 19 (41%), increased mechanical pain sensitivity in 12 (26%) and allodynia in 16 (35%) of 46 survivors. Only 7 survivors (15%) had pathologic NCS. QST is a sensitive tool that revealed signs of large-fiber neuropathy in two thirds, small-fiber neuropathy and pain sensitization in one third of survivors. Prospective studies using QST in pediatric oncology may help to elucidate the pathophysiology of small-fiber neuropathy and pain sensitization as well as their relevance for quality of survival. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

TNF-Alpha in Peripheral Neuropathy Patients with Impaired Glucose Regulation.

PubMed

Li, Xia; Zhu, Ju; Liu, Na; Liu, Jie; Zhang, Zhecheng

2017-01-01

Impaired glucose regulation (IGR) is the prestate of diabetes; about 1/3 of IGR patients will develop to diabetes finally. In this study, we investigated the serum tumor necrosis factor-alpha (TNF- α ) and interleukin-6 (IL-6) levels in peripheral neuropathy impaired patients with impaired glucose regulation (IGR). A total of 70 IGR patients received the conventional nerve conduction test, including 30 patients with peripheral neuropathy (PN) and 40 patients without peripheral neuropathy (NPN). The other 40 healthy individuals were recruited as controls. The serum TNF- α and IL-6 in IGR patients were higher than in control group, and serum TNF- α and IL-6 levels in IGR-PN group were higher than in IGR-NPN group (27.7 ± 17.8 versus 13.1 ± 6.7 pg/mL and 18.1 ± 17.7 versus 6.4 ± 3.7 pg/mL, resp., both p < 0.05). Multifactors logistic regression analysis showed that TNF- α (OR = 0.893; p = 0.009) was an independent factor affecting whether IGR could combine with peripheral neuropathy. TNF- α and IL-6 could aggregate peripheral neuropathy in impaired glucose regulation patients; TNF- α might be independent risk factor for peripheral neuropathy in glucose regulation impaired patients.

Monoclonal Gammopathy Associated Peripheral Neuropathy: Diagnosis and Management

PubMed Central

Chaudhry, Hafsa M.; Mauermann, Michelle L.; Rajkumar, S. Vincent

2017-01-01

Monoclonal gammopathies consist of a spectrum of clonal plasma cell disorders that includes monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenstrom Macroglobulinemia (WM). In this review, we outline the epidemiology, etiology, classification, diagnosis, and treatment of monoclonal gammopathy associated peripheral neuropathy. Monoclonal gammopathy of undetermined significance (MGUS) is relatively common in the general population, with a prevalence of 3–4% among those over the age of 50. Therefore, the presence of M protein in a patient with neuropathy does not automatically indicate a causal relationship. Monoclonal gammopathy associated peripheral neuropathy is often a difficult diagnosis with limited treatment options. Studies addressing the optimal approach to diagnosis and management of this entity are limited. In addition to a review of the literature, we present a diagnostic approach to patients with monoclonal gammopathy associated peripheral neuropathy and discuss available data and options for treatment. PMID:28473042

Efficacy and Safety of Pregabalin in the Treatment of Patients With Painful Diabetic Peripheral Neuropathy and Pain on Walking.

PubMed

Huffman, Cynthia; Stacey, Brett R; Tuchman, Michael; Burbridge, Claire; Li, Chunming; Parsons, Bruce; Pauer, Lynne; Scavone, Joseph M; Behar, Regina; Yurkewicz, Lorraine

2015-11-01

This randomized, double-blind, placebo-controlled, multicenter, 2-period crossover study (two 6-week treatment periods separated by a 2-week washout period) evaluated the efficacy and safety of pregabalin (150 to 300 mg/d) for treatment of pain and pain on walking in patients with painful diabetic peripheral neuropathy (DPN) who experienced pain while walking. Co-primary efficacy endpoints were: (1) mean pain score (last 7 daily pain diary scores, 0 to 10 numeric rating scale at end of each treatment period) and (2) DPN pain on walking (0 to 10 numeric rating scale immediately after walking 50 feet [15.2 m] on flat surface). Secondary endpoints included other pain parameters, patient-reported sleep, health-related quality of life, and safety measures. Two hundred three patients were treated (pregabalin, n=198; placebo, n=186), with no statistically significant treatment difference for pregabalin versus placebo in the co-primary efficacy endpoints, mean DPN pain (P=0.0656) and mean DPN pain on walking (P=0.412). A carryover effect was observed. Analysis of co-primary endpoints for period 1 showed significant treatment difference for DPN pain (P=0.034) and DPN pain on walking (P=0.001). Treatment with pregabalin resulted in significant improvements versus placebo on prespecified patient global impression of change (end of period 1; P=0.002), and sleep interference rating scale (end of period 2; P=0.011). Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 13 (6.6%) pregabalin patients versus 5 (2.7%) placebo patients. Failure to meet the co-primary objectives may be related to carryover effect from period 1 to period 2, lower pregabalin dose (150 to 300 mg/d), and/or placebo response in painful DPN.

High resolution ultrasonography of the tibial nerve in diabetic peripheral neuropathy.

PubMed

Singh, Kunwarpal; Gupta, Kamlesh; Kaur, Sukhdeep

2017-12-01

High-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy. 75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs. The mean cross sectional area (22.63 +/- 2.66 mm 2 ) and maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score ( p < 0.001). The diabetic patients with no signs of peripheral neuropathy had a larger mean cross sectional area (14.40 +/- 1.72 mm 2 ) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/- 1.01 mm 2 and 0.30 mm respectively). The cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.

Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy.

PubMed

Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka

2015-11-01

Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P < 0.05). We also tested whether there is an association between peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P < 0.05), with the strongest association being with motor neuropathy (P < 0.001). Our data from cells and from patients with breast cancer suggest that 1-deoxysphingolipids, the very-long-chain in particular, play a role as molecular intermediates of paclitaxel-induced peripheral neuropathy. © FASEB.

Efficiencies of Low-Level Laser Therapy (LLLT) and Gabapentin in the Management of Peripheral Neuropathy: Diabetic Neuropathy.

PubMed

Abdel-Wahhab, Khaled G; Daoud, Eitedal M; El Gendy, Aliaa; Mourad, Hagar H; Mannaa, Fathia A; Saber, Maha M

2018-03-12

Diabetic neuropathy (DN) is the highly occurred complication of diabetes mellitus; it has been defined as an event of peripheral nerve dysfunction characterized by pain, allodynia, hyperalgesia, and paraesthesia. The current study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) in the management of neuropathy in diabetic rats. The used animals were divided into the following groups: negative control, streptozotocin-induced diabetic rats, and diabetic rats with peripheral neuropathy (DNP) and DNP treated with gabapentin or with LLLT. Behavioral tests were carried out through hotplate test for the determination of pain sensations and the Morris water maze test for spatial reference memory evaluation. Blood samples were collected at the end of treatment for biochemical determinations. In the current study, the latency of hind-paw lick decreased significantly when DNP are treated with gabapentin or LLLT. The Morris water maze test showed that LLLT treatment improved memory that deteriorated in DNP more than gabapentin do. The results of the biochemical study revealed that LLLT could not affect the level of beta-endorphin that decreased in DNP but significantly decreased S100B that rose in DNP. PGE2 and cytokines IL-1β, IL-10, and TNF-α showed significant increase in DNP compared with control group. The gabapentin administration or LLLT application significantly reversed the levels of the mentioned markers towards the normal values of the controls. Levels of serum MDA and nitric oxide increased significantly in the DNP but rGSH showed significant decrease. These markers were improved significantly when the DNP were treated with gabapentin or LLLT. The treatment with gabapentin or LLLT significantly decreased the raised level in total cholesterol in DNP but could not decrease the elevated level of triglycerides, while LDL cholesterol decreased significantly in DNP treated with gabapentin but not affected by LLLT. Values of serum alanine

Duloxetine contributing to a successful multimodal treatment program for peripheral femoral neuropathy and comorbid 'reactive depression' in an adolescent.

PubMed

Kachko, Ludmyla; Ben Ami, Shiri; Liberman, Alon; Birk, Einat; Kronenberg, Sefi

2011-01-01

In the United States, duloxetine has been approved for the treatment of major depressive disorder, diabetic peripheral neuropathic pain and fibromyalgia in the adult population. Data regarding the use of duloxetine in the pediatric population, however, are very limited. Femoral nerve injury is a rare complication of cardiac catheterization. In the case described, duloxetine contributed to a successful multimodal treatment program for peripheral neuropathic pain due to femoral neuropathy in an adolescent with 'reactive depression' and conversion symptoms. To the best of the authors' knowledge, the present article is only the third such report on this dual use of duloxetine in children and adolescents, and the first report of such treatment following femoral neuropathy induced by cardiac catheterization.

Changes in the basal membrane of dorsal root ganglia Schwann cells explain the biphasic pattern of the peripheral neuropathy in streptozotocin-induced diabetic rats.

PubMed

Becker, Maria; Benromano, Tali; Shahar, Abraham; Nevo, Zvi; Pick, Chaim G

2014-12-01

Peripheral neuropathy is one of the main complications of diabetes mellitus. The current study demonstrated the bimodal pattern of diabetic peripheral neuropathy found in the behavioral study of pain perception in parallel to the histopathological findings in dorsal root ganglia (DRGs) neurons and satellite Schwann cell basement membranes. A gradual decrease in heparan sulfate content, with a reciprocal increase in deposited laminin in the basement membranes of dorsal root ganglia Schwann cells, was shown in streptozotocin-treated rats. In addition, the characteristic biphasic pain profiles were demonstrated in diabetic rats, as shown by hypersensitivity at the third week and hyposensitivity at the tenth week post-streptozotocin injection, accompanied by a continuous decrease in the sciatic nerve conduction velocity. It appears that these basal membrane abnormalities in content of heparan sulfate and laminin, noticed in diabetic rats, may underline the primary damage in dorsal ganglion sensory neurons, simultaneously with the bimodal painful profile in diabetic peripheral neuropathy, simulating the scenario of filtration rate in diabetic kidney.

Electrochemical skin conductance to detect sudomotor dysfunction, peripheral neuropathy and the risk of foot ulceration among Saudi patients with diabetes mellitus.

PubMed

Sheshah, Eman; Madanat, Amal; Al-Greesheh, Fahad; Al-Qaisi, Dalal; Al-Harbi, Mohammad; Aman, Reem; Al-Ghamdi, Abdul Aziz; Al-Madani, Khaled

2015-01-01

Sudomotor dysfunction is manifested clinically as abnormal sweating leading to dryness of feet skin and increased risk of foot ulceration. The aim of this study was to test the performance of foot electrochemical skin conductance (ESC) to detect diabetic peripheral neuropathy and the risk of foot ulceration against traditional methods in Saudi patients with diabetes mellitus. This cross-sectional study was conducted on 296 Saudi patients with diabetes mellitus. Painful neuropathic symptoms were evaluated using the neuropathy symptom score (NSS). The risk of foot ulceration and diabetic peripheral neuropathy were determined using the neuropathy disability score (NDS). Vibration perception threshold (VPT) was assessed using neurothesiometer. Neurophysiological assessment of the right and left sural, peroneal and tibial nerves was performed in 222 participants. Diabetic peripheral neuropathy was defined according to the definition of the American Academy of Neurology. ESC was measured with Sudoscan. Feet-ESC decreased as the scores of sensory and motor function tests increased. Feet-ESC decreased as the NSS, NDS and severity of diabetic peripheral neuropathy increased. Sensitivity of feet-ESC < 50μS to detect diabetic peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 90.1, 61 and 63.8 % respectively and specificity 77, 85 and 81.9 % respectively. Sensitivity of feet-ESC < 70μS to detect diabetic peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 100, 80.6 and 80.9 % respectively. Sensitivity and specificity of feet-ESC < 70μS to detect confirmed-diabetic peripheral neuropathy were 67.5 and 58.9 % respectively. Sudoscan a simple and objective tool can be used to detect diabetic peripheral neuropathy and the risk of foot ulceration among patients with diabetes mellitus. Prospective studies to confirm our results are warranted.

Text Messaging to Improve Disease Management in Patients With Painful Diabetic Peripheral Neuropathy.

PubMed

Bauer, Victoria; Goodman, Nancy; Lapin, Brittany; Cooley, Camille; Wang, Ed; Craig, Terri L; Glosner, Scott E; Juhn, Mark S; Cappelleri, Joseph C; Sadosky, Alesia B; Masi, Christopher

2018-06-01

Purpose The purpose of the study was to determine the impact of educational text messages on diabetes self-management activities and outcomes in patients with painful diabetic peripheral neuropathy (pDPN). Methods Patients with pDPN identified from a large integrated health system who agreed to participate were randomized to 6 months of usual care (UC) or UC plus twice-daily diabetes self-management text messages (UC+TxtM). Outcomes included the Pain Numerical Rating Scale, Summary of Diabetes Self-Care Activities (SDSCA), questions on diabetes health beliefs, and glycated hemoglobin (A1C). Changes from baseline were evaluated at 6 months and compared between groups. Results Demographic characteristics were balanced between groups (N = 62; 53% female, mean age = 63 years, 94% type 2 diabetes), as were baseline measures. After 6 months, pain decreased with UC+TxtM from 6.3 to 5.5 and with UC from 6.5 to 6.0, with no difference between groups. UC+TxtM but not UC was associated with significant improvements from baseline on all SDSCA subscales. On diabetes health beliefs, UC+TxtM patients reported significantly increased benefits and reduced barriers and susceptibility relative to UC at 6 months. A1C declined in both groups, but neither change was significant relative to baseline. Conclusions Patients with pDPN who receive twice-daily text messages regarding diabetes management reported reduced pain relative to baseline, although this change was not significant compared with usual care. In addition, text messaging was associated with increased self-management activities and improved diabetes health beliefs and total self-care. These results warrant further investigation.

Intravenous Lidocaine: Old-School Drug, New Purpose—Reduction of Intractable Pain in Patients with Chemotherapy Induced Peripheral Neuropathy

PubMed Central

van der Wal, Selina E. I.; Smedes, Lotte A.; Radema, Sandra A.; van Alfen, Nens; Steegers, Monique A. H.

2017-01-01

Background. Treatment of intractable pain due to chemotherapy induced peripheral neuropathy (CIPN) is a challenge. Intravenous (iv) lidocaine has shown to be a treatment option for neuropathic pain of different etiologies. Methods. Lidocaine (1.5 mg/kg in 10 minutes followed by 1.5 mg/kg/h over 5 hours) was administered in nine patients with CIPN, and analgesic effect was evaluated during infusion and after discharge. The immediate effect of lidocaine on pressure pain thresholds (PPT) and the extent of the stocking and glove distribution of sensory abnormalities (cold and pinprick) were assessed. Results. Lidocaine had a significant direct analgesic effect in 8 out of 9 patients (P = 0.01) with a pain intensity difference of >30%. Pain reduction persisted in 5 patients for an average of 23 days. Lidocaine did not influence mean PPT, but there was a tendency that the extent of sensory abnormalities decreased after lidocaine. Conclusion. Iv lidocaine has direct analgesic effect in CIPN with a moderate long-term effect and seems to influence the area of cold and pinprick perception. Additional research is needed, using a control group and larger sample sizes to confirm these results. PMID:28458593

Mild peripheral neuropathy prevents both leg muscular ischaemia and activation of exercise-induced coagulation in Type 2 diabetic patients with peripheral artery disease.

PubMed

Piarulli, F; Sambataro, M; Minicuci, N; Scarano, L; Laverda, B; Baiocchi, M R; Baldo-Enzi, G; Galasso, S; Bax, G; Fedele, D

2007-10-01

To study the influence of peripheral neuropathy on intermittent claudication in patients with Type 2 diabetes (T2DM). Twenty-five patients with T2DM were grouped according to the ankle/brachial index (ABI): 10 with ABI > 0.9 without peripheral artery disease (PAD; group T2DM) and 15 with ABI < 0.9 with PAD (group T2DM + PAD). Twelve individuals without T2DM with PAD (group PAD without T2DM) were also enrolled. Tests for peripheral neuropathy were performed in all patients. ABI, rate pressure product, prothrombin fragments 1 + 2 (F1+2), thrombin-anti-thrombin complex (TAT), and d-dimer were measured before and after a treadmill test. During exercise both initial and absolute claudication distance and electrocardiogram readings were recorded. We found mild peripheral neuropathy in 20% of group T2DM and 46.7% of group T2DM + PAD (P < 0.01). After exercise, the rate pressure product increased in each group; ABI fell in T2DM + PAD (P < 0.0001) and in PAD without T2DM (P = 0.0005); the fall was greater in the latter group. Initial and absolute claudication distances were similar in PAD patients. In group T2DM + PAD, absolute claudication distance was longer in the subgroup without peripheral neuropathy (P < 0.05), whereas ABI and rate pressure products were similar. F1+2 values at rest were higher in group T2DM + PAD. After exercise, F1+2 values and TAT increased only in group PAD without T2DM. Only group PAD without T2DM experienced muscular ischaemia, whereas group T2DM + PAD did not. Mild peripheral neuropathy may have prevented them from reaching the point of muscular ischaemia during the treadmill test, because they stopped exercising with the early onset of pain. Reaching a false absolute claudication distance may induce ischaemic preconditioning. These findings suggest a possible protective role of mild peripheral neuropathy in T2DM patients with intermittent claudication, by preventing further activation of coagulation during treadmill testing.

Peripheral neuropathy is associated with more frequent falls in Parkinson's disease.

PubMed

Beaulieu, Mélanie L; Müller, Martijn L T M; Bohnen, Nicolaas I

2018-04-03

Peripheral neuropathy is a common condition in the elderly that can affect balance and gait. Postural imbalance and gait difficulties in Parkinson's disease (PD), therefore, may stem not only from the primary neurodegenerative process but also from age-related medical comorbidities. Elucidation of the effects of peripheral neuropathy on these difficulties in PD is important to provide more targeted and effective therapy. The purpose of this study was to investigate the association between lower-limb peripheral neuropathy and falls and gait performance in PD while accounting for disease-specific factors. From a total of 140 individuals with PD, 14 male participants met the criteria for peripheral neuropathy and were matched 1:1 for Hoehn & Yahr stage and duration of disease with 14 male participants without peripheral neuropathy. All participants underwent fall (retrospectively) and gait assessment, a clinical evaluation, and [ 11 C]dihydrotetrabenazine and [ 11 C]methylpiperidin-4-yl propionate PET imaging to assess dopaminergic and cholinergic denervation, respectively. The presence of peripheral neuropathy was significantly associated with more falls (50% vs. 14%, p = 0.043), as well as a shorter stride length (p = 0.011) and greater stride length variability (p = 0.004), which resulted in slower gait speed (p = 0.016) during level walking. There was no significant difference in nigrostriatal dopaminergic denervation, cortical and thalamic cholinergic denervation, and MDS-UPDRS motor examination scores between groups. Lower-limb peripheral neuropathy is significantly associated with more falls and gait difficulties in PD. Thus, treating such neuropathy may reduce falls and/or improve gait performance in PD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Subacute peripheral and optic neuropathy syndrome with no evidence of a toxic or nutritional cause.

PubMed

Allen, D; Riordan-Eva, P; Paterson, R W; Hadden, R D M

2013-08-01

The syndrome of subacute simultaneous peripheral neuropathy and bilateral optic neuropathy is known to occur in tropical countries, probably due to malnutrition or toxicity, but not often seen in developed countries. We report seven patients in London who were not malnourished or alcoholic, and in whom no clear cause was found. We retrospectively reviewed the case notes and arranged some further investigations. All patients developed peripheral and bilateral optic neuropathy within 6 months. Patients were aged 30-52, and all of Jamaican birth and race but lived in the UK. Most had subacute, painful ataxic sensory axonal neuropathy or neuronopathy, some with myelopathy. Nerve conduction studies revealed minor demyelinating features in two cases. The optic neuropathy was symmetrical, subacute and monophasic, usually with marked reduction in visual acuity. CSF protein concentration was usually elevated but other laboratory investigations were normal. Patients showed only modest improvement at follow-up. These patients share a common clinical and electrophysiological phenotype, age, ethnicity and elevated CSF protein, but otherwise normal laboratory investigations. The syndrome is a cause of significant morbidity in young people. The cause remains uncertain despite thorough investigation. Copyright © 2013 Elsevier B.V. All rights reserved.

Mobile phone generated vibrations used to detect diabetic peripheral neuropathy.

PubMed

May, Jonathan David; Morris, Matthew William John

2017-12-01

In the current United Kingdom population the incidence of diabetic peripheral neuropathy is increasing. The presence of diabetic neuropathy affects decision making and treatment options. This study seeks to evaluate if the vibrations generated from a mobile phone can be used to screen patients for diabetic peripheral neuropathy. This study comprised of 61 patients; a control group of 21 patients; a lower limb injury group of 19 patients; a diabetic peripheral neuropathy group of 21 patients. The control and injury group were recruited randomly from fracture clinics. The diabetic peripheral neuropathy group were randomly recruited from the diabetic foot clinic. The 61 patients were examined using a 10g Semmes-Weinstein monofilament, a 128Hz tuning fork and a vibrating mobile phone. The points tested were, index finger, patella, lateral malleoli, medial malleoli, heel, first and fifth metatarsal heads. The most accurate location of all the clinical tests was the head of the 1st metatarsal at 0.86. The overall accuracy of the tuning fork was 0.77, the ten gram monofilament 0.79 and the mobile phone accuracy was 0.88. The control group felt 420 of 441 tests (95%). The injury group felt 349 of 399 tests (87%). The neuropathic group felt 216 of 441 tests (48%). There is a significant difference in the number of tests felt between the control and both the injury and neuropathic groups. p<0.0001 using N-1 Two Proportion Test. A mobile phone is an accurate screening tool for diabetic peripheral neuropathy. The most accurate location to test for diabetic peripheral neuropathy is the head of the 1st metatarsal. Screening for diabetic peripheral neuropathy in the index finger and patella were inaccurate. An injury to the lower limb affects the patient's vibration sensation, we would therefore recommend screening the contralateral limb to the injury. This study represents level II evidence of a new diagnostic investigation. Copyright © 2016 European Foot and Ankle Society. All

Sweet bee venom pharmacopuncture for chemotherapy-induced peripheral neuropathy.

PubMed

Yoon, Jeungwon; Jeon, Ju-Hyun; Lee, Yeon-Weol; Cho, Chong-Kwan; Kwon, Ki-Rok; Shin, Ji-Eun; Sagar, Stephen; Wong, Raimond; Yoo, Hwa-Seung

2012-08-01

Chemotherapy-induced peripheral neuropathy (CIPN) is sensory and motor nerve damage to the peripheral nervous system caused by chemotherapeutic agents. It often causes pain and other varying degrees of neuropathic symptoms accompanied by functional limitations and reduced quality of life. Currently, there is no standard treatment protocol for the treatment of CIPN. In need of more research to develop new therapeutic options focusing on their safety, efficacy, and long-term sustained clinical effects, a pilot study of sweet bee venom pharmacopuncture (SBVP) for CIPN was conducted to build up preliminary efficacy data in the process of preparing for a future larger scale randomized controlled SBVP trial for CIPN. We conducted a prospective case series by analyzing the clinical observations made of CIPN patients treated with SBVP. A total of 11 eligible consecutive CIPN patients who visited East-West Cancer Center from June 1, 2010, to February 28, 2011, were treated with total of six SBVP treatments given within the 3-week period. The outcomes were measured using World Health Organization Common Toxicity Criteria for Peripheral neuropathy (WHO grading system), Patient Neurotoxicity Questionnaire (PNQ), Visual Analogue System (VAS), and Health-Related Quality of Life (HRQOL) collected at the baseline, post-second, fourth, and the final treatment. Patients were followed 3 weeks into no intervention to determine the sustained effects of pharmacopuncture. Both of the WHO CIPN grade and PNQ scores have shown a decrease in the level of neuropathy. VAS pain level has also shown a great decrease and improvement in patients' quality of life have also been detected though modest. Changes in WHO grade, VAS and Total HRQOL scores between the baseline and after the last treatment session were significant. Changes in WHO grade, Total PNQ, PNQ-sensory, VAS, Total HRQOL, and HRQOL-functional scores between the baseline and the 3-week follow-up were significant. The positive result

F wave index: A diagnostic tool for peripheral neuropathy.

PubMed

Sathya, G R; Krishnamurthy, N; Veliath, Susheela; Arulneyam, Jayanthi; Venkatachalam, J

2017-03-01

Each skeletal muscle is usually supplied by two or more nerve roots and if one nerve root is affected and the other is spared, the clinically used F wave minimum latency can still be normal. An F wave index was constructed taking into consideration the other parameters of the F wave such as persistence, chronodispersion, latency, arm-length to determine its usefulness in the diagnosis of peripheral neuropathy. This study was undertaken to construct the F wave index in the upper limb for the median nerve in normal healthy adult males and in patients with peripheral neuropathy and to compare the values obtained in both groups. This hospital-based study was carried out on 40 males who were diagnosed to have peripheral neuropathy and on 40 age matched healthy males who served as the control group. The F wave recording was done using a digitalized nerve conduction/electromyography/EP machine in a quiet and dimly lit room. All recordings were done between 0900 and 1100 h at an ambient temperature of 22°C. The F wave recording was obtained from a fully relaxed muscle by stimulating the median nerve. The median value for F wave index obtained from median nerve (abductor pollicis brevis) in patients with peripheral neuropathy [right arm - 35.85, interquartile range (IQR) - 35.26; left arm - 39.49, IQR - 39.49] was significantly lower (P=0.001) as compared to the control group (right arm - 102.62, IQR - 83.76; left arm - 77.43, IQR - 58.02). Our results showed that F wave index in upper limb was significantly lower in patients with peripheral neuropathy than the healthy controls, and could be used for early detection of peripheral neuropathy.

Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy

PubMed Central

Komatsu, Masaaki; Wheeler, Heather E.; Chung, Suyoun; Low, Siew-Kee; Wing, Claudia; Delaney, Shannon M.; Gorsic, Lidija K.; Takahashi, Atsushi; Kubo, Michiaki; Kroetz, Deanna L.; Zhang, Wei; Nakamura, Yusuke; Dolan, M. Eileen

2015-01-01

Purpose Paclitaxel is used worldwide in the treatment of breast, lung, ovarian and other cancers. Sensory peripheral neuropathy is an associated adverse effect that cannot be predicted, prevented or mitigated. To better understand the contribution of germline genetic variation to paclitaxel-induced peripheral neuropathy, we undertook an integrative approach that combines genome-wide association study (GWAS) data generated from HapMap lymphoblastoid cell lines (LCLs) and Asian patients. Methods GWAS was performed with paclitaxel-induced cytotoxicity generated in 363 LCLs and with paclitaxel-induced neuropathy from 145 Asian patients. A gene-based approach was used to identify overlapping genes and compare to a European clinical cohort of paclitaxel-induced neuropathy. Neurons derived from human induced pluripotent stem cells were used for functional validation of candidate genes. Results SNPs near AIPL1 were significantly associated with paclitaxel-induced cytotoxicity in Asian LCLs (P < 10−6). Decreased expression of AIPL1 resulted in decreased sensitivity of neurons to paclitaxel by inducing neurite morphological changes as measured by increased relative total outgrowth, number of processes and mean process length. Using a gene-based analysis, there were 32 genes that overlapped between Asian LCL cytotoxicity and Asian patient neuropathy (P < 0.05) including BCR. Upon BCR knockdown, there was an increase in neuronal sensitivity to paclitaxel as measured by neurite morphological characteristics. Conclusion We identified genetic variants associated with Asian paclitaxel-induced cytotoxicity and functionally validated the AIPL1 and BCR in a neuronal cell model. Furthermore, the integrative pharmacogenomics approach of LCL/patient GWAS may help prioritize target genes associated with chemotherapeutic-induced peripheral neuropathy. PMID:26015512

A community-based epidemiological study of peripheral neuropathies in Assiut, Egypt.

PubMed

Kandil, Mahmoud R; Darwish, Esam S; Khedr, Eman M; Sabry, Mahmoud M; Abdulah, Mohamed A

2012-12-01

There is very little published information about the prevalence, patterns, and predictors of peripheral neuropathies. The current study is a community-based survey was conducted in the Assiut Governorate to estimate their prevalence and clinical profile. A door-to-door study was carried out on 42,223 persons from rural and urban communities in the Assiut Governorate, Egypt. There were 13,288 (31.5%) subjects from the urban and 28,935 (68·5%) from the rural area. All subjects filled in a questionnaire designed specifically for diagnosis of peripheral neuropathy. Positive cases were then given a complete medical and neurological examination, routine laboratory tests, neurophysiology, and neuroimaging (magnetic resonance). The crude prevalence rate (CPR) of peripheral neuropathy was 3181/100,000 inhabitants. There was a significantly higher prevalence in the rural compared with the urban population (3795 versus 1844/100,000) and in females than males (4473 versus 1943/100,000; P<0.001 for both). The most common type reported was entrapment neuropathy (736 cases with CPR of 1743/100,000), particularly carpal tunnel syndrome (1686/100,000). Diabetic neuropathy was the most common non-compressive neuropathy with a CPR of 649/100,000. Type II diabetes was recorded in 241 patients with a CPR of 571/100,000. Compressive radiculopathy had a crude prevalence of 358/100,000; traumatic and iatrogenic radiculopathy had a prevalence rate of 149/100,000. Less common conditions were: uremic neuropathy (21/100,000) hepatic neuropathy (14/100,000), Bell's palsy (28/100,000), Guillian-Barre' syndrome (12/100,000), chronic inflammatory demyelinating polyneuropathy (12/100,000), hereditary sensory motor neuropathy (12/100,000), and idiopathic neuropathy (92/100,000). The overall prevalence of peripheral neuropathies was high in comparison to other studies. Entrapment neuropathy, diabetic neuropathy, and spondylotic radiculopathy were the most common. Overall, the prevalence of

Perspectives on the impact of painful diabetic peripheral neuropathy in a multicultural population.

PubMed

Eichholz, Martin; Alexander, Andrea H; Cappelleri, Joseph C; Hlavacek, Patrick; Parsons, Bruce; Sadosky, Alesia; Tuchman, Michael M

2017-01-01

Since few studies have characterized painful diabetic peripheral neuropathy (pDPN) symptoms in multicultural populations, this study fielded a survey to better understand pDPN and its impact in African-American, Caucasian, and Hispanic populations. Kelton fielded a survey by phone or Internet, in English or Spanish, among adults with pDPN symptoms in the United States between August and October 2015; African-Americans and Hispanics were oversampled to achieve at least 500 subjects for each group. Patients were required to have been diagnosed with pDPN or score ≥ 3 on ID Pain validated screening tool. The survey elicited information on pDPN symptoms and interactions with healthcare providers (HCPs), and included the Brief Pain Inventory and pain-specific Work Productivity and Assessment Questionnaire (WPAI:SHP). Respondents included 823 Caucasians, 525 African-Americans, and 537 Hispanics; approximately half of African-Americans and Hispanics were <40 years of age, vs 12% of Caucasians. Pain was less likely to be rated moderate or severe by African-Americans (65%) and Hispanics (49%) relative to Caucasians (87%; p  < 0.05). African-Americans and Hispanics were less likely than Caucasians to report experiencing specific pDPN sensory symptoms. Significantly fewer African-Americans and Hispanics reported receiving a pDPN diagnosis relative to Caucasians ( p  < 0.05), and higher proportions of African-Americans and Hispanics reported difficulty communicating with their HCP ( p  < 0.05). WPAI:SHP activity impairment was lower in Hispanics (43%) relative to African-Americans (53%) and Caucasian (56%; p  < 0.05). Multicultural patients reported differences in pDPN symptoms and pain relative to Caucasians, and fewer received a pDPN diagnosis. While further evaluation is needed to understand these differences, these data suggest a need to broaden pDPN educational initiatives to improve patient-HCP dialogue and encourage discussion of pDPN symptoms and

Analysis of youtube as a source of information for peripheral neuropathy.

PubMed

Gupta, Harsh V; Lee, Ricky W; Raina, Sunil K; Behrle, Brian L; Hinduja, Archana; Mittal, Manoj K

2016-01-01

YouTube is an important resource for patients. No study has evaluated the information on peripheral neuropathy disseminated by YouTube videos. In this study, our aim was to perform a systematic review of information on YouTube regarding peripheral neuropathy. The Web site (www.youtube.com) was searched between September 19 and 21, 2014, for the terms "neuropathy," "peripheral neuropathy," "diabetic neuropathy," "neuropathy causes," and "neuropathy treatment." Two hundred videos met the inclusion criteria. Healthcare professionals accounted for almost half of the treatment videos (41 of 92; 44.6%), and most came from chiropractors (18 of 41; 43.9%). Alternative medicine was cited most frequently among the treatment discussions (54 of 145, 37.2%), followed by devices (38 of 145, 26.2%), and pharmacological treatments (23 of 145, 15.9%). Approximately half of the treatment options discussed in the videos were not evidence-based. Caution should be exercised when YouTube videos are used as a patient resource. © 2015 Wiley Periodicals, Inc.

Regulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Kawata, Daisuke; Wu, Zetang

2017-09-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet)-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2), and expression of the transgene was controlled by doxycycline (DOX). We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.

The association of vitamin D with inflammatory cytokines in diabetic peripheral neuropathy.

PubMed

Bilir, Bulent; Tulubas, Feti; Bilir, Betul Ekiz; Atile, Neslihan Soysal; Kara, Sonat Pinar; Yildirim, Tulay; Gumustas, Seyit Ali; Topcu, Birol; Kaymaz, Ozlem; Aydin, Murat

2016-07-01

[Purpose] The effects of vitamin D on the circulating levels of IL-17 and IL-13 were investigated in patients with diabetic peripheral neuropathy, patients with diabetes mellitus type 2 without neuropathy, and healthy controls. [Subjects and Methods] A single-blind controlled clinical study was performed, including70 type 2 diabetic patients with or without diabetic peripheral neuropathy and 33 healthy volunteer controls. The 25(OH)D levels were evaluated using ultra-performance liquid chromatography, and IL-17 and IL-13 levels were assessed using enzyme-linked immunosorbent assays. [Results] The 25(OH) vitamin D concentration was lower in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy and healthy controls. Similarly, 25(OH)D levels were lower in diabetes mellitus patients than healthy controls. IL-17 and IL-13 levels were higher in diabetes mellitus patients than in controls. Additionally, IL-13 levels were higher in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy. These differences were statistically significant. There was a significant positive correlation between 25(OH)D and IL-13,and a negative correlation between 25(OH)D andIL-17 in the diabetic and diabetic neuropathy groups. [Conclusion] Vitamin D is a potential modifiable risk factor for diabetic peripheral neuropathy and may regulate inflammatory mediators, e.g., IL-17 and IL-13.

Cryotherapy in Preventing Peripheral Neuropathy and Nail Toxicity in Patients With Breast Cancer Who Are Receiving Paclitaxel

ClinicalTrials.gov

2018-01-09

Chemotherapeutic Agent Toxicity; Pain; Peripheral Neuropathy; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Therapy-related Toxicity

Early-Onset Physical Frailty in Adults with Diabesity and Peripheral Neuropathy.

PubMed

Tuttle, Lori J; Bittel, Daniel C; Bittel, Adam J; Sinacore, David R

2017-12-07

Diabesity (obesity and diabetes mellitus) has been identified as a potential contributor to early-onset frailty. Impairments contributing to early onset of physical frailty in this population are not well understood, and there is little evidence of the impact of peripheral neuropathy on frailty. The purpose of this study was to determine impairments that contribute to early-onset physical frailty in individuals with diabesity and peripheral neuropathy. We studied 105 participants, 82 with diabesity and peripheral neuropathy (57 years of age, body mass index [BMI] 31 kg/m 2 ); 13 with diabesity only (53 years of age, BMI 34 kg/m 2 ) and 10 obese controls (67 years of age, BMI 32 kg/m 2 ). Peripheral neuropathy was determined using Semmes Weinstein monofilaments; physical frailty was classified using the 9-item, modified Physical Performance Test; and knee extension and ankle plantarflexion peak torques were measured using isokinetic dynamometry. Participants with diabesity and peripheral neuropathy were 7.4 times more likely to be classified as physically frail. Impairments in lower-extremity function were associated with classification of frailty. Individuals with diabesity and peripheral neuropathy are particularly likely to be classified as frail. Earlier identification and interventions aimed at improving lower-extremity function may be important to mitigate the early-onset functional decline. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Peripheral neuropathy in Tangier disease: A literature review and assessment.

PubMed

Mercan, Metin; Yayla, Vildan; Altinay, Serdar; Seyhan, Serhat

2018-06-01

Tangier disease (TD) (OMIM#205400) is a rare cause of inherited metabolic neuropathies characterized by marked deficiency of high-density lipoproteins and accumulation of cholesterol esters in various tissue resulting from reverse cholesterol transport deficiency. We report a case of a patient with TD with multifocal demyelinating neuropathy with conduction block who presents with winging scapula, tongue, and asymmetric extremity weakness. We also present a review of all studies published from 1960 to 2017 regarding peripheral neuropathy in TD. Our search identified 54 patients with TD with peripheral neuropathy. Syringomyelia-like neuropathy subtype (52.4%) was more frequent than multifocal sensorial and motor neuropathy subtype (26.2%), focal neuropathy subtype (19.1%), and distal symmetric polyneuropathy subtype (2.4%). Splenomegaly was the most common (40.7%) clinical manifestation in these patients. The pattern of electrodiagnostic abnormalities are: (1) demyelinating abnormalities were more predominant in the upper extremities than in the lower extremities and (2) slowing of motor nerve conduction was more prominent in the intermediate segment than in distal nerve segments. The sural-sparing pattern was present in 34.6% and conduction block was present in 11.5% of the patients. Our literature review and our case showed the clinical spectrum of TD neuropathy is quite wide and that it should be considered in the differential diagnosis of non-uniform demyelinating neuropathies. © 2018 Peripheral Nerve Society.

Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy.

PubMed

Turkiew, Elliot; Falconer, Debbie; Reed, Nicole; Höke, Ahmet

2017-09-01

Distal axon degeneration seen in many peripheral neuropathies is likely to share common molecular mechanisms with Wallerian degeneration. Although several studies in mouse models of peripheral neuropathy showed prevention of axon degeneration in the slow Wallerian degeneration (Wlds) mouse, the role of a recently identified player in Wallerian degeneration, Sarm1, has not been explored extensively. In this study, we show that mice lacking the Sarm1 gene are resistant to distal axonal degeneration in a model of chemotherapy induced peripheral neuropathy caused by paclitaxel and a model of high fat diet induced putative metabolic neuropathy. This study extends the role of Sarm1 to axon degeneration seen in peripheral neuropathies and identifies it as a likely target for therapeutic development. © 2017 Peripheral Nerve Society.

Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature.

PubMed

Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P

2018-03-01

The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated, but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy, with most cases (31/40) receiving a >42 g total (>4 weeks) of therapy. In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0 to 50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 g total (>4 weeks) of metronidazole compared with those patients receiving ≤42 g total (17.9% vs. 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is rare in patients who receive ≤42 g total of metronidazole. Patients who receive higher total doses may be at higher risk of peripheral neuropathy, but symptoms resolve after discontinuation of therapy in most patients. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 g total of the drug (≤4 weeks). Published by Elsevier B.V.

Topiramate induced peripheral neuropathy: A case report and review of literature.

PubMed

Hamed, Sherifa Ahmed

2017-12-16

Drug-induced peripheral neuropathy had been rarely reported as an adverse effect of some antiepileptic drugs (AEDs) at high cumulative doses or even within the therapeutic drug doses or levels. We describe clinical and diagnostic features of a patient with peripheral neuropathy as an adverse effect of chronic topiramate (TPM) therapy. A 37-year-old woman was presented for the control of active epilepsy (2010). She was resistant to some AEDs as mono- or combined therapies (carbamazepine, sodium valproate, levetiracetam, oxcarbazepine and lamotrigine). She has the diagnosis of frontal lobe epilepsy with secondary generalization and has a brother, sister and son with active epilepsies. She became seizure free on TPM (2013-2017) but is complaining of persistent distal lower extremities paresthesia in a stocking distribution. Neurological examination revealed presence of diminished Achilles tendon reflexes, stocking hypesthesia and delayed distal latencies, reduced conduction velocities and amplitudes of action potentials of posterior tibial and sural nerves, indicating demyelinating and axonal peripheral neuropathy of the lower extremities. After exclusion of the possible causes of peripheral neuropathy, chronic TPM therapy is suggested as the most probable cause of patient's neuropathy. This is the first case report of topiramate induced peripheral neuropathy in the literature.

Peripheral Glial Cells in the Development of Diabetic Neuropathy.

PubMed

Gonçalves, Nádia Pereira; Vægter, Christian Bjerggaard; Pallesen, Lone Tjener

2018-01-01

The global prevalence of diabetes is rapidly increasing, affecting more than half a billion individuals within the next few years. As diabetes negatively affects several physiological systems, this dramatic increase represents not only impaired quality of life on the individual level but also a huge socioeconomic challenge. One of the physiological consequences affecting up to half of diabetic patients is the progressive deterioration of the peripheral nervous system, resulting in spontaneous pain and eventually loss of sensory function, motor weakness, and organ dysfunctions. Despite intense research on the consequences of hyperglycemia on nerve functions, the biological mechanisms underlying diabetic neuropathy are still largely unknown, and treatment options lacking. Research has mainly focused directly on the neuronal component, presumably from the perspective that this is the functional signal-transmitting unit of the nerve. However, it is noteworthy that each single peripheral sensory neuron is intimately associated with numerous glial cells; the neuronal soma is completely enclosed by satellite glial cells and the length of the longest axons covered by at least 1,000 Schwann cells. The glial cells are vital for the neuron, but very little is still known about these cells in general and especially how they respond to diabetes in terms of altered neuronal support. We will discuss current knowledge of peripheral glial cells and argue that increased research in these cells is imperative for a better understanding of the mechanisms underlying diabetic neuropathy.

Peripheral Glial Cells in the Development of Diabetic Neuropathy

PubMed Central

Gonçalves, Nádia Pereira; Vægter, Christian Bjerggaard; Pallesen, Lone Tjener

2018-01-01

The global prevalence of diabetes is rapidly increasing, affecting more than half a billion individuals within the next few years. As diabetes negatively affects several physiological systems, this dramatic increase represents not only impaired quality of life on the individual level but also a huge socioeconomic challenge. One of the physiological consequences affecting up to half of diabetic patients is the progressive deterioration of the peripheral nervous system, resulting in spontaneous pain and eventually loss of sensory function, motor weakness, and organ dysfunctions. Despite intense research on the consequences of hyperglycemia on nerve functions, the biological mechanisms underlying diabetic neuropathy are still largely unknown, and treatment options lacking. Research has mainly focused directly on the neuronal component, presumably from the perspective that this is the functional signal-transmitting unit of the nerve. However, it is noteworthy that each single peripheral sensory neuron is intimately associated with numerous glial cells; the neuronal soma is completely enclosed by satellite glial cells and the length of the longest axons covered by at least 1,000 Schwann cells. The glial cells are vital for the neuron, but very little is still known about these cells in general and especially how they respond to diabetes in terms of altered neuronal support. We will discuss current knowledge of peripheral glial cells and argue that increased research in these cells is imperative for a better understanding of the mechanisms underlying diabetic neuropathy. PMID:29770116

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy.

PubMed

Köşkderelioğlu, Aslı; Ortan, Pınar; Ari, Alpay; Gedizlioğlu, Muhteşem

2016-03-01

To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy

PubMed Central

KÖŞKDERELİOĞLU, Aslı; ORTAN, Pınar; ARI, Alpay; GEDİZLİOĞLU, Muhteşem

2016-01-01

Introduction To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Methods Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Results Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Conclusion Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients

Diagnosis and therapeutic options for peripheral vasculitic neuropathy

PubMed Central

2015-01-01

Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia

PubMed Central

Pitceathly, Robert D. S.; Blake, Julian C.; Woodward, Catherine E.; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E.; Plant, Gordon T.; Houlden, Henry; Sweeney, Mary G.; Hanna, Michael G.; Reilly, Mary M.

2014-01-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P < 0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P = 0.002; odds ratio 8.43, 95% confidence

Correlation of Michigan neuropathy screening instrument, United Kingdom screening test and electrodiagnosis for early detection of diabetic peripheral neuropathy.

PubMed

Fateh, Hamid R; Madani, Seyed Pezhman; Heshmat, Ramin; Larijani, Bagher

2015-01-01

Almost half of Diabetic Peripheral Neuropathies (DPNs) are symptom-free. Methods including questionnaires and electrodiagnosis (EDx) can be fruitful for easy reach to early diagnosis, correct treatments of diabetic neuropathy, and so decline of complications for instance diabetic foot ulcer and prevention of high costs. The goal of our study was to compare effectiveness of the Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST) and electrophysiological evaluation in confirming diabetic peripheral neuropathy. One hundred twenty five known diabetes mellitus male and female subjects older than 18 with or without symptoms of neuropathy comprised in this research. All of them were interviewed in terms of demographic data, lipid profile, HbA1C, duration of disease, and history of retinopathy, so examined by Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST), and nerve conduction studies (NCS). The collected data were analyzed by SPSS software 18. One hundred twenty five diabetic patients (70 female, 55 male) were recruited in this study with a mean age of 58.7 ± 10.2, and mean duration of diabetes was 10.17 ± 6.9 years. The mean neuropathy score of MNSI and UKST were 2.3 (1.7) and 4.16 (2.9), respectively. Each instrument detected the peripheral neuropathy in 78 (69 %) and 91 (73 %) of patients, respectively. There was a significant relationship between number of neuropathies and mean of diabetes duration and development of retinopathy in both questionnaire evaluations and NCS. By nerve conduction study, neuropathy was detected in 121 (97 %) diabetic patients were reported in order 15 (12 %) mononeuropathy (as 33 % sensory and 67 % motor neuropathy) and 106 (85 %) polyneuropathy (as 31 % motor and 69 % sensorimotor neuropathy). As regards NCS is an objective, simple, and non-invasive tool and also can determine level of damage and regeneration in peripheral nerves, this study

Side Effects: Nerve Problems (Peripheral Neuropathy)

Cancer.gov

Nerve problems, such as peripheral neuropathy, can be caused by cancer treatment. Learn about signs and symptoms of nerve changes. Find out how to prevent or manage nerve problems during cancer treatment.

Assessment Tools for Peripheral Neuropathy in Pediatric Oncology: A Systematic Review From the Children's Oncology Group.

PubMed

Smolik, Suzanne; Arland, Lesley; Hensley, Mary Ann; Schissel, Debra; Shepperd, Barbara; Thomas, Kristin; Rodgers, Cheryl

Peripheral neuropathy is a known side effect of several chemotherapy agents, including vinca alkaloids and platinum-based chemotherapy. Early recognition and monitoring of this side effect is an important role of the pediatric oncology nurse. There are a variety of peripheral neuropathy assessment tools currently in use, but the usefulness of these tools in identifying and grading neuropathy in children varies, and there is currently no standardized tool in place to evaluate peripheral neuropathy in pediatric oncology. A systematic review was performed to identify the peripheral neuropathy assessment tools that best evaluate the early onset and progression of peripheral neuropathy in pediatric patients receiving vincristine. Because of the limited information available in pediatric oncology, this review was extended to any pediatric patient with neuropathy. A total of 8 studies were included in the evidence synthesis. Based on available evidence, the pediatric-modified Total Neuropathy Scale (ped-m TNS) and the Total Neuropathy Score-pediatric version (TNS-PV) are recommended for the assessment of vincristine-induced peripheral neuropathy in children 6 years of age and older. In addition, several studies demonstrated that subjective symptoms alone are not adequate to assess for vincristine-induced peripheral neuropathy. Nursing assessment of peripheral neuropathy should be an integral and regular part of patient care throughout the course of chemotherapy treatment.

The Importance of Rare Subtypes in Diagnosis and Treatment of Peripheral Neuropathy: A Review.

PubMed

Callaghan, Brian C; Price, Raymond S; Chen, Kevin S; Feldman, Eva L

2015-12-01

Peripheral neuropathy is a prevalent condition that usually warrants a thorough history and examination but has limited diagnostic evaluation. However, rare localizations of peripheral neuropathy often require more extensive diagnostic testing and different treatments. To describe rare localizations of peripheral neuropathy, including the appropriate diagnostic evaluation and available treatments. References were identified from PubMed searches conducted on May 29, 2015, with an emphasis on systematic reviews and randomized clinical trials. Articles were also identified through the use of the authors' own files. Search terms included common rare neuropathy localizations and their causes, as well as epidemiology, pathophysiology, diagnosis, and treatment. Diffuse, nonlength-dependent neuropathies, multiple mononeuropathies, polyradiculopathies, plexopathies, and radiculoplexus neuropathies are rare peripheral neuropathy localizations that often require extensive diagnostic testing. Atypical neuropathy features, such as acute/subacute onset, asymmetry, and/or motor predominant signs, are frequently present. The most common diffuse, nonlength-dependent neuropathies are Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and amyotrophic lateral sclerosis. Effective disease-modifying therapies exist for many diffuse, nonlength-dependent neuropathies including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and some paraprotein-associated demyelinating neuropathies. Vasculitic neuropathy (multiple mononeuropathy) also has efficacious treatment options, but definitive evidence of a treatment effect for IgM anti-MAG neuropathy and diabetic amyotrophy (radiculoplexus neuropathy) is lacking. Recognition of rare localizations of peripheral neuropathy is essential given the implications for diagnostic testing and treatment. Electrodiagnostic studies are an important

Carpal tunnel syndrome: just a peripheral neuropathy?

PubMed

Fernández-de-Las-Peñas, César; Plaza-Manzano, Gustavo

2018-06-05

Carpal tunnel syndrome (CTS) is considered just a peripheral neuropathy of the upper extremity associated to the compression of the median nerve. There is evidence suggesting the presence of complex sensitization mechanisms in CTS. These processes are manifested by symptoms in extra-median regions and the presence of bilateral sensory and motor impairments. These sensory and motor changes are not associated to electrodiagnostic findings. The presence of sensitization mechanisms suggests that CTS should not be considered just as a peripheral neuropathy. The presence of altered nociceptive gain processing should be considered for therapeutic management of CTS by considering the application of therapeutic interventions that modulate nociceptive barrage into the CNS.

Prevalence and predictors of peripheral neuropathy in nondiabetic children with chronic kidney disease.

PubMed

Yoganathan, Sangeetha; Bagga, Arvind; Gulati, Sheffali; Toteja, G S; Hari, Pankaj; Sinha, Aditi; Pandey, Ravindra Mohan; Irshad, Mohammad

2018-05-01

This study sought to determine the prevalence and predictors of peripheral neuropathy in nondiabetic children with chronic kidney disease (CKD). Fifty-one consecutive normally nourished children, 3-18 years of age, with CKD stages IV and V of nondiabetic etiology were enrolled from May to December 2012. Nerve conduction studies were performed in 50 children. Blood samples were analyzed for the biochemical parameters, trace elements, and micronutrients. The prevalence of peripheral neuropathy in our cohort was 52% (95% confidence interval 37.65, 66.34). The majority (80.8%) of the children had axonal neuropathy, and 11.5% had demyelinating neuropathy. Isolated motor neuropathy was identified in 92.3% of the children, and sensorimotor neuropathy was identified in 7.6%. The significant risk factors associated with peripheral neuropathy were older age, low serum copper, and dialysis therapy. Electrodiagnostic studies should be performed in children with CKD to assess for peripheral neuropathy for the purpose of optimizing medical care. Muscle Nerve 57: 792-798, 2018. © 2017 Wiley Periodicals, Inc.

Immunostaining of skin biopsy adds no diagnostic value in MGUS-associated peripheral neuropathy.

PubMed

Al-Zuhairy, Ali; Schrøder, Henrik Daa; Plesner, Torben; Abildgaard, Niels; Sindrup, Søren H

2015-02-15

For several decades an association between MGUS, IgM-MGUS in particular, and peripheral neuropathy has been suspected. Several histopathology studies have shown binding of IgM to myelin and a secondary widening of myelin lamellae in cutaneous nerves and in the sural nerve of patients with IgM-MGUS, or Waldenström's Macroglobulinaemia (WM), and peripheral neuropathy. In this retrospective study we investigated the value of skin biopsy examination in the diagnosis of MGUS- and WM-associated peripheral neuropathy. A total of 117 patients, who were examined for an M-component in serum with associated nerve symptoms, had a skin biopsy taken and examined for immunoglobulin deposition in cutaneous nerves. Thirty-five patients were diagnosed with MGUS or WM and peripheral neuropathy with no other cause of neuropathy. Nineteen patients had MGUS but no peripheral neuropathy. Of the 35 patients with MGUS or WM and peripheral neuropathy, four had immunoglobulin deposition in the skin biopsy, all of whom had an IgM gammopathy. In the control group of 19 without peripheral neuropathy, three had immunoglobulin deposition in the skin biopsy, all of whom had IgM-MGUS. In both groups, there was a trend towards higher IgM blood levels in patients with immunoglobulin deposition. Half of the patients with IgM gammopathy in the neuropathy group had anti-MAG reactivity, whereas only one in the control group had weak anti-MAG reactivity. Our study indicates that examination of skin biopsies for immunoglobulin deposition does not add significant diagnostic value in the evaluation of neuropathies suspected to be caused by MGUS or WM. IgM immunoglobulin deposition in skin biopsy might merely be an epiphenomenon secondary to high IgM blood levels. Copyright © 2014 Elsevier B.V. All rights reserved.

Peripheral neuropathy: an often-overlooked cause of falls in the elderly.

PubMed

Richardson, J K; Ashton-Miller, J A

1996-06-01

Peripheral neuropathy is common in the elderly and results in impairments in distal proprioception and strength that hinder balance and predispose them to falls. The loss of heel reflexes, decreased vibratory sense that improves proximally, impaired position sense at the great toe, and inability to maintain unipedal stance for 10 seconds in three attempts all suggest functionally significant peripheral neuropathy. Physicians can help their patients with peripheral neuropathy to prevent falls by teaching them and their families about peripheral nerve dysfunction and its effects on balance and by advising patients to substitute vision for the lost somatosensory function, correctly use a cane, wear proper shoes and orthotics, and perform balance and upper extremity strengthening exercises.

Electrophysiological measurements of diabetic peripheral neuropathy: A systematic review.

PubMed

Shabeeb, Dheyauldeen; Najafi, Masoud; Hasanzadeh, Gholamreza; Hadian, Mohammed Reza; Musa, Ahmed Eleojio; Shirazi, Alireza

2018-03-28

Peripheral neuropathy is one of the main complications of diabetes mellitus. One of the features of diabetic nerve damage is abnormality of sensory and motor nerve conduction study. An electrophysiological examination can be reproduced and is also a non-invasive approach in the assessment of peripheral nerve function. Population-based and clinical studies have been conducted to validate the sensitivity of these methods. When the diagnosis was based on clinical electrophysiological examination, abnormalities were observed in all patients. In this research, using a review design, we reviewed the issue of clinical electrophysiological examination of diabetic peripheral neuropathy in articles from 2008 to 2017. For this purpose, PubMed, Scopus and Embase databases of journals were used for searching articles. The researchers indicated that diabetes (both types) is a very disturbing health issue in the modern world and should be given serious attention. Based on conducted studies, it was demonstrated that there are different procedures for prevention and treatment of diabetes-related health problems such as diabetic polyneuropathy (DPN). The first objective quantitative indication of the peripheral neuropathy is abnormality of sensory and motor nerve conduction tests. Electrophysiology is accurate, reliable and sensitive. It can be reproduced and also is a noninvasive approach in the assessment of peripheral nerve function. The methodological review has found that the best method for quantitative indication of the peripheral neuropathy compared with all other methods is clinical electrophysiological examination. For best results, standard protocols such as temperature control and equipment calibration are recommended. Copyright © 2018. Published by Elsevier Ltd.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia.

PubMed

Horga, Alejandro; Pitceathly, Robert D S; Blake, Julian C; Woodward, Catherine E; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E; Plant, Gordon T; Houlden, Henry; Sweeney, Mary G; Hanna, Michael G; Reilly, Mary M

2014-12-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P<0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P=0.002; odds ratio 8.43, 95% confidence interval 2

Premature aging-related peripheral neuropathy in a mouse model of progeria.

PubMed

Goss, James R; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D; Glorioso, Joseph C; Niedernhofer, Laura J

2011-08-01

Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1(-/Δ) mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1(-/Δ) mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Peripherally Restricted Cannabinoids for the Treatment of Pain.

PubMed

Romero-Sandoval, E Alfonso; Asbill, Scott; Paige, Candler A; Byrd-Glover, Kiara

2015-10-01

The use of cannabinoids for the treatment of chronic diseases has increased in the United States, with 23 states having legalized the use of marijuana. Although currently available cannabinoid compounds have shown effectiveness in relieving symptoms associated with numerous diseases, the use of cannabis or cannabinoids is still controversial mostly due to their psychotropic effects (e.g., euphoria, laughter) or central nervous system (CNS)-related undesired effects (e.g., tolerance, dependence). A potential strategy to use cannabinoids for medical conditions without inducing psychotropic or CNS-related undesired effects is to avoid their actions in the CNS. This approach could be beneficial for conditions with prominent peripheral pathophysiologic mechanisms (e.g., painful diabetic neuropathy, chemotherapy-induced neuropathy). In this article, we discuss the scientific evidence to target the peripheral cannabinoid system as an alternative to cannabis use for medical purposes, and we review the available literature to determine the pros and cons of potential strategies that can be used to this end. © 2015 Pharmacotherapy Publications, Inc.

Meta-analysis of incidence and risk of peripheral neuropathy associated with intravenous bortezomib.

PubMed

Peng, Ling; Ye, Xianghua; Zhou, Yun; Zhang, Junyan; Zhao, Qiong

2015-09-01

Bortezomib is a proteasome inhibitor which has demonstrated activity against recurrent or newly diagnosed multiple myeloma (MM) and mantle cell lymphoma. Peripheral neuropathy has been described with this agent, although the overall incidence and relative risk remain unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy associated with the use of intravenous bortezomib in MM and lymphoma and to compare the relative risk compared with placebo. We searched PubMed, Embase, Cochrane databases, and meeting proceedings from the American Society of Clinical Oncology (ASCO) for relevant clinical trials. Eligible studies included prospective phase 2 and 3 clinical trials with toxicity profile on peripheral neuropathy associated with intravenous bortezomib in patients with MM and lymphoma. Statistical analyses were done to calculate summary incidences, relative risks (RRs), and 95 % confidence intervals (CIs), employing fixed- or random-effects models depending on the heterogeneity of the included studies. Altogether, 34 clinical trials were selected for the meta-analysis, yielding a total of 6492 patients. The incidence of peripheral neuropathy (all grades) was 33.9 % (95 % CI, 29.9-38.5 %) and that of high-grade events was 8.1 % (95 % CI, 6.9-9.4 %). The relative risks of bortezomib-induced peripheral neuropathy compared to placebo were increased for all-grade (RR = 4.89; 95 % CI, 2.52-9.51) and high-grade (RR = 4.53; 95 % CI, 2.04-10.07) peripheral neuropathy (for randomized controlled trials only). Our analysis was also stratified by different underlying diseases, and patients with lymphoma had an increased incidence of all-grade peripheral neuropathy than those with MM when treated with intravenous bortezomib. Treatment with intravenous bortezomib is associated with an increased risk of developing peripheral neuropathy.

Peripheral neuropathy in genetically characterized patients with mitochondrial disorders: A study from south India.

PubMed

Bindu, Parayil Sankaran; Govindaraju, Chikanna; Sonam, Kothari; Nagappa, Madhu; Chiplunkar, Shwetha; Kumar, Rakesh; Gayathri, Narayanappa; Bharath, M M Srinivas; Arvinda, Hanumanthapura R; Sinha, Sanjib; Khan, Nahid Akthar; Govindaraj, Periyasamy; Nunia, Vandana; Paramasivam, Arumugam; Thangaraj, Kumarasamy; Taly, Arun B

2016-03-01

There are relatively few studies, which focus on peripheral neuropathy in large cohorts of genetically characterized patients with mitochondrial disorders. This study sought to analyze the pattern of peripheral neuropathy in a cohort of patients with mitochondrial disorders. The study subjects were derived from a cohort of 52 patients with a genetic diagnosis of mitochondrial disorders seen over a period of 8 years (2006-2013). All patients underwent nerve conduction studies and those patients with abnormalities suggestive of peripheral neuropathy were included in the study. Their phenotypic features, genotype, pattern of peripheral neuropathy and nerve conduction abnormalities were analyzed retrospectively. The study cohort included 18 patients (age range: 18 months-50 years, M:F- 1.2:1).The genotype included mitochondrial DNA point mutations (n=11), SURF1 mutations (n=4) and POLG1(n=3). Axonal neuropathy was noted in 12 patients (sensori-motor:n=4; sensory:n=4; motor:n=4) and demyelinating neuropathy in 6. Phenotype-genotype correlations revealed predominant axonal neuropathy in mtDNA point mutations and demyelinating neuropathy in SURF1. Patients with POLG related disorders had both sensory ataxic neuropathy and axonal neuropathy. A careful analysis of the family history, clinical presentation, biochemical, histochemical and structural analysis may help to bring out the mitochondrial etiology in patients with peripheral neuropathy and may facilitate targeted gene testing. Presence of demyelinating neuropathy in Leigh's syndrome may suggest underlying SURF1 mutations. Sensory ataxic neuropathy with other mitochondrial signatures should raise the possibility of POLG related disorder. Copyright © 2015. Published by Elsevier B.V.

Role of metformin in oxaliplatin-induced peripheral neuropathy in patients with stage III colorectal cancer: randomized, controlled study.

PubMed

El-Fatatry, Basma Mahrous; Ibrahim, Osama Mohamed; Hussien, Fatma Zakaria; Mostafa, Tarek Mohamed

2018-06-21

Peripheral sensory neuropathy is the most prominently reported adverse effect of oxaliplatin. The purpose of this study was to evaluate metformin role in oxaliplatin-induced neuropathy. From November 2014 to May 2016, 40 patients with stage III colorectal cancer completed 12 cycles of FOLFOX-4 regimen. Twenty patients in the control arm received FOLFOX-4 regimen only, and 20 patients in the metformin arm, received the same regimen along with metformin 500 mg three times daily. The metformin efficacy was evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0), a12-item neurotoxicity questionnaire (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group and, the brief pain inventory short form "worst pain" item. In addition to neurotensin, malondialdehyde and interleukin-6 serum levels assessment. At the end of the 12th cycle, there were less patients with grade 2 and 3 neuropathy in metformin arm as compared to control arm. (60 versus 95%, P = 0.009) In addition, metformin arm showed significantly higher total scores of Ntx-12 questionnaire than control arm (24.0 versus 19.2, P < 0.001). Furthermore, the mean pain score in metformin arm was significantly lower than those of control arm, (6.7 versus 7.3, P = 0.005). Mean serum levels of malondialdehyde and neurotensin were significantly lower in metformin arm after the 6th and the 12th cycles. Metformin may be a promising drug in protecting colorectal cancer patients against oxaliplatin-induced chronic peripheral sensory neuropathy.

[Vasculitic Peripheral Neuropathies: Clinical Features and Diagnostic Laboratory Tests].

PubMed

Ogata, Katsuhisa

2016-03-01

Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course.

Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment

PubMed Central

Mo, Michelle; Erdelyi, Ildiko; Szigeti-Buck, Klara; Benbow, Jennifer H.; Ehrlich, Barbara E.

2012-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect that occurs in many patients undergoing chemotherapy. It is often irreversible and frequently leads to early termination of treatment. In this study, we have identified two compounds, lithium and ibudilast, that when administered as a single prophylactic injection prior to paclitaxel treatment, prevent the development of CIPN in mice at the sensory-motor and cellular level. The prevention of neuropathy was not observed in paclitaxel-treated mice that were only prophylactically treated with a vehicle injection. The coadministration of lithium with paclitaxel also allows for administration of higher doses of paclitaxel (survival increases by 60%), protects against paclitaxel-induced cardiac abnormalities, and, notably, does not interfere with the antitumor effects of paclitaxel. Moreover, we have determined a mechanism by which CIPN develops and have discovered that lithium and ibudilast inhibit development of peripheral neuropathy by disrupting the interaction between paclitaxel, neuronal calcium sensor 1 (NCS-1), and the inositol 1,4,5-trisphosphate receptor (InsP3R) to prevent treatment-induced decreases in intracellular calcium signaling. This study shows that lithium and ibudilast are candidate therapeutics for the prevention of paclitaxel-induced neuropathy and could enable patients to tolerate more aggressive treatment regimens.—Mo, M., Erdelyi, I., Szigeti-Buck, K., Benbow, J. H., Ehrlich, B. E. Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment. PMID:22889832

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis.

PubMed

Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

2018-03-28

To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori ( H. pylori ) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve ( R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

PubMed Central

Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

2018-01-01

AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy

High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis.

PubMed

Xue, Hong-Xia; Fu, Wen-Yi; Cui, Hua-Dong; Yang, Li-Li; Zhang, Ning; Zhao, Li-Juan

2015-05-01

Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

PubMed Central

Xue, Hong-xia; Fu, Wen-yi; Cui, Hua-dong; Yang, Li-li; Zhang, Ning; Zhao, Li-juan

2015-01-01

Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide. PMID:26109960

Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

PubMed Central

2011-01-01

Background Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be

Comparison of topical capsaicin and topical turpentine Oil for treatment of painful diabetic neuropathy.

PubMed

Musharraf, Muhammad Usman; Ahmad, Zaheer; Yaqub, Zernab

2017-01-01

Diabetes Mellitus is a pandemic of the modern era owing to our rapidly deteriorating lifestyle. Painful diabetic neuropathy is one of the costliest and disabling complications of diabetes mellitus. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Topical Capsaicin and Turpentine Oil are found to be effective in treatment of painful diabetic neuropathy. Patients of either gender with ages between 18 and 70 years having painful diabetic neuropathy already taking one oral drug for painful neuropathy and treatment for diabetes mellitus and an HbA1C less than 8.5% were included while Pregnant or lactating mothers, patients with chronic liver disease and patients with renal insufficiency (creatinine >3.0 mg/dl) and peripheral arterial disease were excluded from study. Patients were randomly divided into two groups (A & B) using computer generated random number table. Group A was given topical application of capsaicin while Group B was given topical application of commercially available turpentine oil over painful site on feet. 300 patients were equally divided in two groups. The patients in group A had a Visual Analog Pain Score of 7.91±5.10 at baseline and 5.10±1.343 after 3 months of treatment (p-value 0.0001). The patients in group B had a Visual Analog Pain Score of 7.83±1.012 at baseline and 5.20±1.187 after 3 months of treatment (p-value 0.0001). Chi Square test was applied to compare efficacy of both groups. It was noted that 71 (53%) had efficacy in group A and 63 (47%) had efficacy in the group B but the difference was not statistically significant. (p-value=0.399). It has been concluded that turpentine oil is effective in managing diabetic neuropathic pain similar to capsaicin cream.

Peripheral neuropathy is a common manifestation of mitochondrial diseases: a single-centre experience.

PubMed

Luigetti, M; Sauchelli, D; Primiano, G; Cuccagna, C; Bernardo, D; Lo Monaco, M; Servidei, S

2016-06-01

Peripheral neuropathy in mitochondrial diseases (MDs) may vary from a subclinical finding in a multisystem syndrome to a severe, even isolated, manifestation in some patients. To investigate the involvement of the peripheral nervous system in MDs extensive electrophysiological studies were performed in 109 patients with morphological, biochemical and genetic diagnosis of MD [12 A3243G progressive external ophthalmoplegia (PEO)/mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), 16 myoclonic epilepsy with ragged-red fibres (MERRF), four mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), 67 PEO with single or multiple deletions of mitochondrial DNA, 10 others]. A neuropathy was found in 49 patients (45%). The incidence was very high in MNGIE (100%), MELAS (92%) and MERRF (69%), whilst 28% of PEO patients had evidence of peripheral involvement. The most frequent abnormality was a sensory axonal neuropathy found in 32/49 patients (65%). A sensory-motor axonal neuropathy was instead detected in 16% of the patients and sensory-motor axonal demyelinating neuropathy in 16%. Finally one Leigh patient had a motor axonal neuropathy. It is interesting to note that the great majority had preserved tendon reflexes and no sensory disturbances. In conclusion, peripheral involvement in MD is frequent even if often mild or asymptomatic. The correct identification and characterization of peripheral neuropathy through electrophysiological studies represents another tile in the challenge of MD diagnosis. © 2016 EAN.

Role of sigma 1 receptor in high fat diet-induced peripheral neuropathy.

PubMed

Song, Tieying; Zhao, Jianhui; Ma, Xiaojing; Zhang, Zaiwang; Jiang, Bo; Yang, Yunliang

2017-09-26

The neurobiological mechanisms of obesity-induced peripheral neuropathy are poorly understood. We evaluated the role of Sigma-1 receptor (Sig-1R) and NMDA receptor (NMDARs) in the spinal cord in peripheral neuropathy using an animal model of high fat diet-induced diabetes. We examined the expression of Sig-1R and NMDAR subunits GluN2A and GluN2B along with postsynaptic density protein 95 (PSD-95) in the spinal cord after 24-week HFD treatment in both wild-type and Sig-1R-/- mice. Finally, we examined the effects of repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice on peripheral neuropathy. Wild-type mice developed tactile allodynia and thermal hypoalgesia after 24-week HFD treatment. HFD-induced peripheral neuropathy correlated with increased expression of GluN2A and GluN2B subunits of NMDARs, PDS-95, and Sig-1R, as well as increased Sig-1R-NMDAR interaction in the spinal cord. In contrast, Sig-1R-/- mice did not develop thermal hypoalgesia or tactile allodynia after 24-week HFD treatment, and the levels of GluN2A, GluN2B, and PSD-95 were not altered in the spinal cord of HFD-fed Sig-1R-/- mice. Finally, repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice attenuated peripheral neuropathy. Our results suggest that obesity-associated peripheral neuropathy may involve Sig-1R-mediated enhancement of NMDAR expression in the spinal cord.

Exploration of a Novel Persistent Reversal of Pathological Pain: Mechanisms and Mediators

DTIC Science & Technology

2015-04-01

ability of a single IT ATL313 dose to reverse neuropathic pain from traumatic peripheral neuropathy . Milestone 2 is complete. We determined that 1 pmol...cord injury; to prevent and reverse neuropathic pain from inflammatory peripheral neuropathy following either IT or peri-sciatic nerve ( peripheral ...ATL313 can reverse neuropathic pain from inflammatory peripheral neuropathy following either IT or peri-sciatic nerve ( peripheral ) injections. We also

Peripheral neuropathy in patients with myotonic dystrophy type 2.

PubMed

Leonardis, L

2017-05-01

Myotonic dystrophy type 2 (dystrophia myotonica type 2-DM2) is an autosomal dominant multi-organ disorder. The involvement of the peripheral nervous system was found in 25%-45% of patients with myotonic dystrophy type 1, although limited data are available concerning polyneuropathy in patients with DM2, which was the aim of this study with a thorough presentation of the cases with peripheral neuropathy. Patients with genetically confirmed DM2 underwent motor nerve conduction studies of the median, ulnar, tibial and fibular nerves and sensory nerve conduction studies of the median (second finger), ulnar (fifth finger), radial (forearm) and sural nerves. Seventeen adult patients with DM2 participated in the study. Fifty-three percent (9/17) of our patients had abnormality of one or more attributes (latency, amplitude or conduction velocity) in two or more separate nerves. Four types of neuropathies were found: (i) predominantly axonal motor and sensory polyneuropathy, (ii) motor polyneuropathy, (iii) predominantly demyelinating motor and sensory polyneuropathy and (iv) mutilating polyneuropathy with ulcers. The most common forms are axonal motor and sensory polyneuropathy (29%) and motor neuropathy (18% of all examined patients). No correlations were found between the presence of neuropathy and age, CCTG repeats, blood glucose or HbA1C. Peripheral neuropathy is common in patients with DM2 and presents one of the multisystemic manifestations of DM2. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Psychological Factors Associated With Painful Versus Non-Painful HIV-Associated Sensory Neuropathy.

PubMed

Pillay, Prinisha; Wadley, Antonia L; Cherry, Catherine L; Karstaedt, Alan S; Kamerman, Peter R

2018-05-01

HIV-associated sensory neuropathy (HIV-SN) is a common, and frequently painful complication of HIV, but factors that determine the presence of pain are unresolved. We investigated: (i) if psychological factors associated with painful (n = 125) versus non-painful HIV-SN (n = 72), and (ii) if pain and psychological factors affected quality of life (QoL). We assessed anxiety and depression using the Hopkins Symptoms Checklist-25. Pain catastrophizing and QoL were assessed using the Pain Catastrophizing Scale and Euroqol-5D, respectively. Presence of neuropathy was detected using the Brief Neuropathy Screening Tool, and pain was characterised using the Wisconsin Brief Pain Questionnaire. Overall, there was a high burden of pain, depression and anxiety in the cohort. None of the psychological variables associated with having painful HIV-SN. Greater depressive symptoms and presence of pain were independently associated with lower QoL. In those participants with painful HIV-SN, greater depressive symptom scores were associated with increased pain intensity. In conclusion, in a cohort with high background levels of psychological dysfunction, psychological factors do not predict the presence of pain, but both depression and presence of pain are associated with poor quality of life.

Paclitaxel Plasma Concentration after the First Infusion Predicts Treatment-Limiting Peripheral Neuropathy.

PubMed

Hertz, Daniel L; Kidwell, Kelley M; Vangipuram, Kiran; Li, Feng; Pai, Manjunath P; Burness, Monika; Griggs, Jennifer J; Schott, Anne F; Van Poznak, Catherine; Hayes, Daniel F; Lavoie Smith, Ellen M; Henry, N Lynn

2018-04-27

Purpose: Paclitaxel exposure, specifically the maximum concentration ( C max ) and amount of time the concentration remains above 0.05 μmol/L ( T c >0.05 ), has been associated with the occurrence of paclitaxel-induced peripheral neuropathy. The objective of this study was to validate the relationship between paclitaxel exposure and peripheral neuropathy. Experimental Design: Patients with breast cancer receiving paclitaxel 80 mg/m 2 × 12 weekly doses were enrolled in an observational clinical study (NCT02338115). Paclitaxel plasma concentration was measured at the end of and 16-26 hours after the first infusion to estimate C max and T c >0.05 Patient-reported peripheral neuropathy was collected via CIPN20 at each dose, and an 8-item sensory subscale (CIPN8) was used in the primary analysis to test for an association with T c >0.05 Secondary analyses were conducted using C max as an alternative exposure parameter and testing each parameter with a secondary endpoint of the occurrence of peripheral neuropathy-induced treatment disruption. Results: In 60 subjects included in the analysis, the increase in CIPN8 during treatment was associated with baseline CIPN8, cumulative dose, and relative dose intensity ( P < 0.05), but neither T c >0.05 ( P = 0.27) nor C max ( P = 0.99). In analyses of the secondary endpoint, cumulative dose (OR = 1.46; 95% confidence interval (CI), 1.18-1.80; P = 0.0008) and T c >0.05 (OR = 1.79; 95% CI, 1.06-3.01; P = 0.029) or C max (OR = 2.74; 95% CI, 1.45-5.20; P = 0.002) were associated with peripheral neuropathy-induced treatment disruption. Conclusions: Paclitaxel exposure is predictive of the occurrence of treatment-limiting peripheral neuropathy in patients receiving weekly paclitaxel for breast cancer. Studies are warranted to determine whether exposure-guided dosing enhances treatment effectiveness and/or prevents peripheral neuropathy in these patients. Clin Cancer Res; 1-9. ©2018 AACR. ©2018 American Association for Cancer

Pregabalin for painful HIV neuropathy

PubMed Central

Simpson, D. M.; Schifitto, G.; Clifford, D. B.; Murphy, T. K.; Durso-De Cruz, E.; Glue, P.; Whalen, E.; Emir, B.; Scott, G. N.; Freeman, R.

2010-01-01

Objective: Pregabalin is effective in several neuropathic pain syndromes. This trial evaluated its efficacy, safety, and tolerability for treatment of painful HIV-associated neuropathy. Methods: This randomized, double-blind, placebo-controlled, parallel-group trial included a 2-week double-blind dose-adjustment (150–600 mg/day BID) phase, a 12-week double-blind maintenance phase, and an optional 3-month open label extension phase. The primary efficacy measure was the mean Numeric Pain Rating Scale (NPRS) score, an 11-point numeric rating scale. Secondary measures included Patient Global Impression of Change (PGIC) and sleep measurements. Results: Baseline mean NPRS score was 6.93 for patients randomized to pregabalin (n = 151) and 6.72 for those to placebo (n = 151). Pregabalin average daily dosage (SD) was 385.7 (160.3) mg/d. At endpoint, pregabalin and placebo showed substantial reductions in mean NPRS score from baseline: −2.88 vs −2.63, p = 0.3941. Pregabalin had greater improvements in NPRS score relative to placebo at weeks 1 (−1.14 vs −0.69, p = 0.0131) and 2 (−1.92 vs −1.43, p = 0.0393), and at weeks 7 (−3.22 vs −2.53 p = 0.0307) and 8 (−3.33 vs −2.53, p = 0.0156). At all other time points, differences between groups were not significant. Sleep measurements and 7-item PGIC did not differ among treatment groups; however, collapsed PGIC scores showed 82.8% of pregabalin and 66.7% of placebo patients rated themselves in 1 of the 3 “improved” categories (p = 0.0077). Somnolence and dizziness were the most common adverse events with pregabalin. Conclusions: Pregabalin was well-tolerated, but not superior to placebo in the treatment of painful HIV neuropathy. Factors predicting analgesic response in HIV neuropathy warrant additional research. Classification of Evidence: This Class II trial showed that pregabalin is not more effective than placebo in treatment of painful HIV neuropathy. GLOSSARY AE = adverse events; ANCOVA = analysis of

Pharmacological Modulation of the Mitochondrial Electron Transport Chain in Paclitaxel-Induced Painful Peripheral Neuropathy.

PubMed

Griffiths, Lisa A; Flatters, Sarah J L

2015-10-01

Paclitaxel is an effective first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Mitochondrial dysfunction and oxidative stress have been implicated in paclitaxel-induced painful neuropathy. Here we show the effects of pharmacological modulation of mitochondrial sites that produce reactive oxygen species using systemic rotenone (complex I inhibitor) or antimycin A (complex III inhibitor) on the maintenance and development of paclitaxel-induced mechanical hypersensitivity in adult male Sprague Dawley rats. The maximally tolerated dose (5 mg/kg) of rotenone inhibited established paclitaxel-induced mechanical hypersensitivity. However, some of these inhibitory effects coincided with decreased motor coordination; 3 mg/kg rotenone also significantly attenuated established paclitaxel-induced mechanical hypersensitivity without any motor impairment. The maximally tolerated dose (.6 mg/kg) of antimycin A reversed established paclitaxel-induced mechanical hypersensitivity without any motor impairment. Seven daily doses of systemic rotenone or antimycin A were given either after paclitaxel administration or before and during paclitaxel administration. Rotenone had no significant effect on the development of paclitaxel-induced mechanical hypersensitivity. However, antimycin A significantly inhibited the development of paclitaxel-induced mechanical hypersensitivity when given before and during paclitaxel administration but had no effect when given after paclitaxel administration. These studies provide further evidence of paclitaxel-evoked mitochondrial dysfunction in vivo, suggesting that complex III activity is instrumental in paclitaxel-induced pain. This study provides further in vivo evidence that mitochondrial dysfunction is a key contributor to the development and maintenance of chemotherapy-induced painful neuropathy. This work also indicates that selective modulation of the electron transport chain can induce antinociceptive

Mechanisms of Distal Axonal Degeneration in Peripheral Neuropathies

PubMed Central

Cashman, Christopher R.; Höke, Ahmet

2015-01-01

Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478

Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6.

PubMed

Linnemann, Christoph; Tezenas du Montcel, Sophie; Rakowicz, Maryla; Schmitz-Hübsch, Tanja; Szymanski, Sandra; Berciano, Jose; van de Warrenburg, Bart P; Pedersen, Karine; Depondt, Chantal; Rola, Rafal; Klockgether, Thomas; García, Antonio; Mutlu, Gurkan; Schöls, Ludger

2016-04-01

Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers.

Incidence and risk of peripheral neuropathy with nab-paclitaxel in patients with cancer: a meta-analysis.

PubMed

Peng, L; Bu, Z; Ye, X; Zhou, Y; Zhao, Q

2017-09-01

Nab-paclitaxel, a Cremophor EL-free formulation of paclitaxel, is used to treat various malignancies. Peripheral neuropathy is one of its major toxicities, although the overall incidence remains unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy in cancer patients treated with nab-paclitaxel and to compare the relative risk (RR) with conventional taxanes. The electronic databases were searched for relevant clinical trials. Eligible studies included phase II and III prospective clinical trials of cancer patients treated with nab-paclitaxel with toxicity profile on peripheral neuropathy. Statistical analyses were done to calculate summary incidences, RRs and 95% confidence intervals (CI), using fixed-effects or random-effects models based on the heterogeneity of the included studies. Nineteen trials were selected for the meta-analysis, yielding a total of 2878 cancer patients. The overall incidences of peripheral neuropathy (all-grade) was 51.0% (95% CI: 45.1-57.6%), and that of high-grade peripheral neuropathy was 12.4% (9.8-15.7%). The RRs of peripheral neuropathy of nab-paclitaxel compared to taxanes were not increased for all-grade and high-grade peripheral neuropathy. Nab-paclitaxel is associated with an increased risk of developing peripheral neuropathy. Future clinical studies are still needed to investigate the risk reduction and possible use of nab-paclitaxel. © 2015 John Wiley & Sons Ltd.

Peripheral neuropathy in patients with HIV infection: consider dual pathology.

PubMed

Miller, R F; Bunting, S; Sadiq, S T; Manji, H

2002-12-01

Two HIV infected patients presented with peripheral neuropathy, in one patient this was originally ascribed to HIV associated mononeuritis multiplex and in the other to stavudine. Investigations confirmed these diagnoses and in both cases genetic analysis identified a second hereditary aetiology: in the first patient hereditary neuropathy with liability to pressure palsies and in the second hereditary motor and sensory neuropathy.

Effect of Vitamin E on Oxaliplatin-induced Peripheral Neuropathy Prevention: A Randomized Controlled Trial.

PubMed

Salehi, Zeinab; Roayaei, Mahnaz

2015-01-01

Peripheral neuropathy is one of the most important limitations of oxaliplatin base regimen, which is the standard for the treatment of colorectal cancer. Evidence has shown that Vitamin E may be protective in chemotherapy-induced peripheral neuropathy. The aim of this study is to evaluate the effect of Vitamin E administration on prevention of oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. This was a prospective randomized, controlled clinical trial. Patients with colorectal cancer and scheduled to receive oxaliplatin-based regimens were enrolled in this study. Enrolled patients were randomized into two groups. The first group received Vitamin E at a dose of 400 mg daily and the second group observed, until after the sixth course of the oxaliplatin regimen. For oxaliplatin-induced peripheral neuropathy assessment, we used the symptom experience diary questionnaire that completed at baseline and after the sixth course of chemotherapy. Only patients with a score of zero at baseline were eligible for this study. Thirty-two patients were randomized to the Vitamin E group and 33 to the control group. There was no difference in the mean peripheral neuropathy score changes (after - before) between two groups, after sixth course of the oxaliplatin base regimen (mean difference [after - before] of Vitamin E group = 6.37 ± 2.85, control group = 6.57 ± 2.94; P = 0.78). Peripheral neuropathy scores were significantly increased after intervention compared with a base line in each group (P < 0.001). The results from this current trial demonstrate a lack of benefit for Vitamin E in preventing oxaliplatin-induced peripheral neuropathy.

Diabetic neuropathy: Clinical manifestations and current treatments

PubMed Central

Callaghan, Brian C.; Cheng, Hsinlin; Stables, Catherine L.; Smith, Andrea L.; Feldman, Eva L.

2014-01-01

Diabetic peripheral neuropathy is a prevalent, disabling condition. The most common manifestation is a distal symmetric polyneuropathy (DSP), but many patterns of nerve injury can occur. Currently, the only effective treatments are glucose control and pain management. While glucose control dramatically decreases the development of neuropathy in those with type 1 diabetes, the effect is likely much smaller in those with type 2 diabetes. High levels of evidence support the use of certain anticonvulsants and antidepressants for pain management in diabetic peripheral neuropathy. However, the lack of disease modifying therapies for diabetic DSP makes the identification of new modifiable risk factors essential. Intriguingly, growing evidence supports an association between metabolic syndrome components, including pre-diabetes, and neuropathy. Future studies are needed to further explore this relationship with implications for new treatments for this common disease. PMID:22608666

Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial

PubMed Central

Smith, Ellen M. Lavoie; Pang, Herbert; Cirrincione, Constance; Fleishman, Stewart; Paskett, Electra D.; Ahles, Tim; Bressler, Linda R.; Fadul, Camilo E.; Knox, Chetaye; Le-Lindqwister, Nguyet; Gilman, Paul B.; Shapiro, Charles L.

2013-01-01

Context There are no known effective treatments for painful chemotherapy-induced peripheral neuropathy (CIPN). Objective The primary objective was to determine the effect of duloxetine 60 mg daily on CIPN “average” pain severity Design Randomized, double-blind, placebo-controlled crossover Setting Eight National Cancer Institute (NCI)-funded cooperative research networks recruited patients from community and academic settings between April 2008 and March 2011. Study follow-up was completed July 2012. Patients 231 patients ≥ 25 years of age were randomized (stratified by chemotherapy drug and CIPN comorbid risk) to receive either duloxetine followed by placebo or placebo followed by duloxetine. Eligible patients reported ≥ Grade 1 sensory CIPN per the NCI Common Toxicity Criteria for Adverse Events and ≥ 4/10 average CIPN-related pain following paclitaxel or oxaliplatin treatment. 81% completed the initial treatment period. Intervention The initial treatment consisted of duloxetine/placebo 30mg/one capsule daily for the first week, then 60mg/two capsules for four additional weeks Outcome Measure The primary hypothesis was that duloxetine would be more effective than placebo in decreasing CIPN pain. Pain severity was assessed using the Brief Pain Inventory-Short Form “average pain” item [0 (no pain) – 10 (as bad as can imagine)]. Results Individuals receiving duloxetine as initial treatment (weeks 1–5) reported a larger mean decrease in average pain (1.06; 95% CI: 0.72, 1.40) compared to placebo-treated patients (0.34; 95% CI: 0.01, 0.66) (p = 0.003) (effect size = 0.513). The observed mean difference in the average pain score between the duloxetine and placebo groups was 0.73 (95% CI: 0.26, 1.20). 59% of duloxetine-treated patients compared to 38% of placebo-treated patients reported decreased pain of any amount. Conclusions Among patients with painful CIPN, the use of duloxetine compared with placebo for 5 weeks resulted in a greater reduction in

Influence of dosing times on cisplatin-induced peripheral neuropathy in rats.

PubMed

Seto, Yoshihiro; Okazaki, Fumiyasu; Horikawa, Keiji; Zhang, Jing; Sasaki, Hitoshi; To, Hideto

2016-09-27

Although cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats. CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague-Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. In order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia. It was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy.

Image analysis software for following progression of peripheral neuropathy

NASA Astrophysics Data System (ADS)

Epplin-Zapf, Thomas; Miller, Clayton; Larkin, Sean; Hermesmeyer, Eduardo; Macy, Jenny; Pellegrini, Marco; Luccarelli, Saverio; Staurenghi, Giovanni; Holmes, Timothy

2009-02-01

A relationship has been reported by several research groups [1 - 4] between the density and shapes of nerve fibers in the cornea and the existence and severity of peripheral neuropathy. Peripheral neuropathy is a complication of several prevalent diseases or conditions, which include diabetes, HIV, prolonged alcohol overconsumption and aging. A common clinical technique for confirming the condition is intramuscular electromyography (EMG), which is invasive, so a noninvasive technique like the one proposed here carries important potential advantages for the physician and patient. A software program that automatically detects the nerve fibers, counts them and measures their shapes is being developed and tested. Tests were carried out with a database of subjects with levels of severity of diabetic neuropathy as determined by EMG testing. Results from this testing, that include a linear regression analysis are shown.

Peripheral neuropathies associated with antibodies directed to intracellular neural antigens.

PubMed

Antoine, J-C

2014-10-01

Antibodies directed to intracellular neural antigens have been mainly described in paraneoplastic peripheral neuropathies and mostly includes anti-Hu and anti-CV2/CRMP5 antibodies. These antibodies occur with different patterns of neuropathy. With anti-Hu antibody, the most frequent manifestation is sensory neuronopathy with frequent autonomic involvement. With anti-CV2/CRMP5 the neuropathy is more frequently sensory and motor with an axonal or mixed demyelinating and axonal electrophysiological pattern. The clinical pattern of these neuropathies is in keeping with the cellular distribution of HuD and CRMP5 in the peripheral nervous system. Although present in high titer, these antibodies are probably not directly responsible for the neuropathy. Pathological and experimental studies indicate that cytotoxic T-cells are probably the main effectors of the immune response. These disorders contrast with those in which antibodies recognize a cell surface antigen and are probably responsible for the disease. The neuronal cell death and axonal degeneration which result from T-cell mediated immunity explains why treating these disorders remains challenging. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pyruvate Dehydrogenase Kinase-mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives Painful Diabetic Neuropathy*

PubMed Central

Rahman, Md Habibur; Jha, Mithilesh Kumar; Kim, Jong-Heon; Nam, Youngpyo; Lee, Maan Gee; Go, Younghoon; Harris, Robert A.; Park, Dong Ho; Kook, Hyun; Lee, In-Kyu; Suk, Kyoungho

2016-01-01

The dorsal root ganglion (DRG) is a highly vulnerable site in diabetic neuropathy. Under diabetic conditions, the DRG is subjected to tissue ischemia or lower ambient oxygen tension that leads to aberrant metabolic functions. Metabolic dysfunctions have been documented to play a crucial role in the pathogenesis of diverse pain hypersensitivities. However, the contribution of diabetes-induced metabolic dysfunctions in the DRG to the pathogenesis of painful diabetic neuropathy remains ill-explored. In this study, we report that pyruvate dehydrogenase kinases (PDK2 and PDK4), key regulatory enzymes in glucose metabolism, mediate glycolytic metabolic shift in the DRG leading to painful diabetic neuropathy. Streptozotocin-induced diabetes substantially enhanced the expression and activity of the PDKs in the DRG, and the genetic ablation of Pdk2 and Pdk4 attenuated the hyperglycemia-induced pain hypersensitivity. Mechanistically, Pdk2/4 deficiency inhibited the diabetes-induced lactate surge, expression of pain-related ion channels, activation of satellite glial cells, and infiltration of macrophages in the DRG, in addition to reducing central sensitization and neuroinflammation hallmarks in the spinal cord, which probably accounts for the attenuated pain hypersensitivity. Pdk2/4-deficient mice were partly resistant to the diabetes-induced loss of peripheral nerve structure and function. Furthermore, in the experiments using DRG neuron cultures, lactic acid treatment enhanced the expression of the ion channels and compromised cell viability. Finally, the pharmacological inhibition of DRG PDKs or lactic acid production substantially attenuated diabetes-induced pain hypersensitivity. Taken together, PDK2/4 induction and the subsequent lactate surge induce the metabolic shift in the diabetic DRG, thereby contributing to the pathogenesis of painful diabetic neuropathy. PMID:26769971

Reflexology in the management of chemotherapy induced peripheral neuropathy: A pilot randomized controlled trial.

PubMed

Kurt, Seda; Can, Gulbeyaz

2018-02-01

The current experimental study aimed to evaluate the effectiveness of reflexology on the management of symptoms and functions of chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients. This study was conducted as a randomized controlled trial in 60 patients (30 experimental and 30 control patients) who had chemotherapy-induced Grade II-IV peripheral neuropathy complaints from July 2013 to November 2015. Data were collected using the patient identification form, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (EORTC-CIPN-20) form, and BPI (used for related chemotherapy-induced peripheral neuropathy symptoms). The majority of the patients were being treated for gastrointestinal or breast cancer and were primarily receiving Eloxatine- or taxane-based treatment. It was found that reflexology applications did not lead to differences in either group in terms of peripheral neuropathy severity and incidence (p > 0.05) and only led to improvement in sensory functions in the experimental group (p < 0.05). It was determined that reflexology is not an effective method in the management of patients' activity levels, walking ability etc. and motor, autonomic functions related CIPN, but reflexology is effective method in the management of patients' sensory functions related CIPN. Key Words: Peripheral neuropathy, reflexology, chemotherapy, EORTC QLQ-CIPN-20, BPI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Vitamin E on Oxaliplatin-induced Peripheral Neuropathy Prevention: A Randomized Controlled Trial

PubMed Central

Salehi, Zeinab; Roayaei, Mahnaz

2015-01-01

Background: Peripheral neuropathy is one of the most important limitations of oxaliplatin base regimen, which is the standard for the treatment of colorectal cancer. Evidence has shown that Vitamin E may be protective in chemotherapy-induced peripheral neuropathy. The aim of this study is to evaluate the effect of Vitamin E administration on prevention of oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. Methods: This was a prospective randomized, controlled clinical trial. Patients with colorectal cancer and scheduled to receive oxaliplatin-based regimens were enrolled in this study. Enrolled patients were randomized into two groups. The first group received Vitamin E at a dose of 400 mg daily and the second group observed, until after the sixth course of the oxaliplatin regimen. For oxaliplatin-induced peripheral neuropathy assessment, we used the symptom experience diary questionnaire that completed at baseline and after the sixth course of chemotherapy. Only patients with a score of zero at baseline were eligible for this study. Results: Thirty-two patients were randomized to the Vitamin E group and 33 to the control group. There was no difference in the mean peripheral neuropathy score changes (after − before) between two groups, after sixth course of the oxaliplatin base regimen (mean difference [after − before] of Vitamin E group = 6.37 ± 2.85, control group = 6.57 ± 2.94; P = 0.78). Peripheral neuropathy scores were significantly increased after intervention compared with a base line in each group (P < 0.001). Conclusions: The results from this current trial demonstrate a lack of benefit for Vitamin E in preventing oxaliplatin-induced peripheral neuropathy. PMID:26682028

Peripheral Sensory Neuropathy and associated factors among adult diabetes mellitus patients in Bahr Dar, Ethiopia.

PubMed

Jember, Gashaw; Melsew, Yayehirad Alemu; Fisseha, Berihu; Sany, Kedir; Gelaw, Asmare Yitayeh; Janakiraman, Balamurugan

2017-01-01

Diabetic sensory neuropathy is a common form of microvascular complication among diabetic patients. The swiftly growing population of people living with diabetes in Ethiopia and lack of elaborated scientific data on peripheral sensory neuropathy among diabetic population in Ethiopia prompted this work. This study was set out to assess the enormity and associated factors of peripheral sensory neuropathy among diabetes patients attending chronic illness clinic of Felege Hiwot Regional Referral Hospital, Bahr Dar, Northwest Ethiopia. An institution based cross-sectional study was conducted at Felege Hiwot Referral Hospital chronic illness clinic using Michigan neuropathy screening instrument tool for diabetic peripheral sensory neuropathy on 408 diabetic patients during 2016. Data were collected using interview, patient record review, anthropometric measurements and physical examination. Both bivariate and multivariate binary logistic regression was employed to identify factors associated with peripheral sensory neuropathy. Odds ratios with their 95% CI and P value less than 0.05 used to determine statistically significant associations. A total of 368 patients were included with the mean age of 49 ± 14.3 years. The overall prevalence of Peripheral Sensory Neuropathy was found to be 52.2%. The major associated factors identified by multivariate analysis were age >50 years: AOR: 3.0 CI [1.11, 7.89]; overweight and obese: AOR: 7.3 CI [3.57, 14.99]; duration of DM: AOR: 3.4 CI [1.75, 6.60]; not involved in physical exercise: AOR: 4.8 CI [1.90, 7.89]; male gender: AOR: 2.4 CI [1.18, 5.05]. Almost half of the diabetic patients who attended Felege Hiwot regional referral hospital during study period were found to present with peripheral sensory neuropathy. Socio-demographic and bio characteristics like patients age, Body Mass Index, level of physical activity and marital status were significantly associated with diabetic peripheral sensory neuropathy.

Peripheral neuropathy in a diabetic child treated with linezolid for multidrug-resistant tuberculosis: a case report and review of the literature.

PubMed

Swaminathan, Aravind; du Cros, Philipp; Seddon, James A; Mirgayosieva, Shamsiya; Asladdin, Rajabov; Dusmatova, Zulfiya

2017-06-12

Extensively drug-resistant (XDR) tuberculosis (TB) and multidrug resistant (MDR)-TB with additional resistance to injectable agents or fluoroquinolones are challenging to treat due to lack of available, effective drugs. Linezolid is one of the few drugs that has shown promise in treating these conditions. Long-term linezolid use is associated with toxicities such as peripheral and optic neuropathies. Diabetes mellitus (DM), especially when uncontrolled, can also result in peripheral neuropathy. The global burden of DM is increasing, and DM has been associated with a three-fold increased risk of developing TB disease. TB and DM can be a challenging combination to treat. DM can inhibit the host immune response to tuberculosis infection; and TB and some anti-TB drugs can worsen glycaemic control. A child experiencing neuropathy that is a possible complication of both DM and linezolid used to treat TB has not been reported previously. We report peripheral neuropathy in a 15-year-old boy with type 1 DM, diagnosed with MDR-TB and additional resistance to injectable TB medications. The boy was treated with a linezolid-based regimen, but after 8 months developed peripheral neuropathy. It was unclear whether the neuropathy was caused by the DM or the linezolid therapy. He had clinical improvement following cessation of linezolid and was declared cured following 21 months of treatment. Following completion of treatment, nerve conduction studies demonstrated significant improvement in neuropathy. To the best of our knowledge, this is the first case of peripheral neuropathy reported in a diabetic child on long-term linezolid therapy for tuberculosis. This case study underlines the importance of stringent follow-up for side effects of linezolid, especially when associated with co-morbidity such as DM that increases the chances of adverse effects. The presence of both DM and TB should alert a physician to strive for optimal glycaemic control to minimize the risk of

Peripheral neuropathy, decreased muscle strength and obesity are strongly associated with walking in persons with type 2 diabetes without manifest mobility limitations.

PubMed

van Sloten, Thomas T; Savelberg, Hans H C M; Duimel-Peeters, Inge G P; Meijer, Kenneth; Henry, Ronald M A; Stehouwer, Coen D A; Schaper, Nicolaas C

2011-01-01

We evaluated the associations of diabetic complications and underlying pathology with daily walking activity in type 2 diabetic patients without manifest mobility limitations. 100 persons with type 2 diabetes (mean age 64.5 ± 9.4 years) were studied. Persons with manifest mobility limitations were excluded. Possible determinants measured: peripheral neuropathy, neuropathic pain, peripheral arterial disease, cardiovascular disease, decreased muscle strength (handgrip strength), BMI, depression, falls and fear of falling. Walking activity was measured during one week with a pedometer. Functional capacity was measured with the 6 min walk test, the timed "up and go" test and a stair climbing test. prevalence of neuropathy (40%) and obesity (53%) was high. Persons took a median of 6429 steps/day. In multivariate regression analysis, adjusted for age and sex, neuropathy was associated with a reduction of 1967 steps/day, decreased muscle strength with 1782 steps/day, and an increase in BMI of 1 kg/m(2) with a decrease of 210 steps/day (all p<0.05). Decreased muscle strength and BMI, but not neuropathy, were associated with outcome of functional capacity tests in multiple regression analysis. peripheral neuropathy, decreased muscle strength and obesity are strongly associated with walking in persons with type 2 diabetes without manifest mobility limitations. 2010 Elsevier Ireland Ltd. All rights reserved.

Incidence and relative risk of peripheral neuropathy in cancer patients treated with eribulin: a meta-analysis.

PubMed

Peng, Ling; Hong, Yun; Ye, Xianghua; Shi, Peng; Zhang, Junyan; Wang, Yina; Zhao, Qiong

2017-12-19

Eribulin is a microtubule inhibitor, which is approved for the treatment of breast cancer. Peripheral neuropathy has been reported in the studies of eribulin, but the incidence and relative risk (RR) of eribulin-associated peripheral neuropathy varied greatly in cancer patients. The purpose of this meta-analysis was to determine the overall incidence and RR of eribulin-associated peripheral neuropathy in cancer patients. Pubmed database and Embase and abstracts presented at the American Society of Clinical Oncology (ASCO) meetings were systematically reviewed for primary studies. Eligible studies included prospective clinical trials and expanded access programs of cancer patients treated with eribulin. Statistical analyses were performed to calculate the incidences, RRs, and 95% confidence intervals (CIs). Altogether, 4,849 patients from 19 clinical trials were selected for this meta-analysis. The incidences of all-grade and high-grade peripheral neuropathy were 27.5% (95% CI: 23.3-32.4%) and 4.7% (95% CI: 3.6-6.2%), respectively. The relative risks of peripheral neuropathy of eribulin compared to control were increased for all-grade (RR = 1.89, 95% CI: 1.10-3.25) but not statistically significant for high-grade (RR = 2.98, 95% CI: 0.71-12.42). The use of eribulin is associated with an increased incidence of peripheral neuropathy. The RR is increased for all-grade peripheral neuropathy.

[Association between neuropathy and peripheral vascular insufficiency in patients with diabetes mellitus type 2].

PubMed

Millán-Guerrero, Rebeca O; Vásquez, Clemente; Isaís-Millán, Sara; Trujillo-Hernández, Benjamín; Caballero-Hoyos, Ramiro

2011-01-01

Diabetes mellitus (DM) can present complications of neuropathy and peripheral arterial disease with high risk for developing foot ulcers and consequent amputations. To identify the association between peripheral vascular disease, and neuropathy in type 2 Diabetes mellitus patients from the Hospital General de Zona No. 1 IMSS in Colima, Mexico. Cross-sectional study of 80 patients with diabetes mellitus evaluated by means of the Edinburgh Claudication Questionnaire, Michigan Neuropathy Screening Instrument, ankle-arm index, Motor Nerve Conduction Velocity and H-reflex. 51 women and 29 men were studied. Mean age was 53.9 +/- 9.6 years, mean diabetes mellitus progression was 8 +/- 6.6 years and mean glucose level was 283 +/- 110 mg/mL. Neuropathy presented in 65 patients (81.2%). Ankle/arm index revealed 19% of patients presented with moderate peripheral vascular insufficiency. Motor Nerve Conduction Velocity was abnormal in 40% of patients and H-reflex was absent in 70%. Grade 2 motor-sensitive polyneuropathy was found in 70-80% of patients and moderate peripheral vascular insufficiency in 19%. It can thus be inferred that the complication of diabetic neuropathy appears before that of peripheral vessel damage.

Improved foot sensitivity and pain reduction in patients with peripheral neuropathy after treatment with monochromatic infrared photo energy--MIRE.

PubMed

Harkless, Lawrence B; DeLellis, Salvatore; Carnegie, Dale H; Burke, Thomas J

2006-01-01

The medical records of 2239 patients (mean age=73 years) with established peripheral neuropathy (PN) were examined to determine whether treatment with MIRE was, in fact, associated with increased foot sensitivity to the Semmes Weinstein monofilament (SWM) 5.07 and a reduction in neuropathic pain. The PN in 1395 of these patients (62%) was due to diabetes. Prior to treatment with MIRE, of the 10 tested sites (5 on each foot), 7.1+/-2.9 were insensitive to the SWM 5.07, and 2078 patients (93%) exhibited loss of protective sensation defined by Medicare as a loss of sensation at two or more sites on either foot. After treatment, the number of insensate sites on both feet decreased to 2.4+/-2.6, an improvement of 66%. Of the 2078 (93%) patients initially presenting with loss of protective sensation, 1106 (53%) no longer had loss of protective sensation after treatment (P<.0001); 1563 patients (70%) also exhibited neuropathic pain in addition to sensory impairment. Prior to treatment with MIRE, pain measured on the 11-point visual analogue scale (VAS) was 7.2+/-2.2 points, despite the use of a variety of pain-relieving therapeutic agents. After treatment with MIRE, pain was reduced by 4.8+/-2.4 points, a 67% reduction. Therefore, MIRE appears to be associated with significant clinical improvement in foot sensation and, simultaneously, a reduction in neuropathic pain in a large cohort of primarily Medicare aged, community-dwelling patients, initially diagnosed with PN. The quality of life associated with these two outcomes cannot be underappreciated.

Performance-based Physical Functioning and Peripheral Neuropathy in a Population-based Cohort of Women at Midlife

PubMed Central

Ylitalo, Kelly R.; Herman, William H.; Harlow, Siobán D.

2013-01-01

Peripheral neuropathy is underappreciated as a potential cause of functional limitations. In the present article, we assessed the cross-sectional association between peripheral neuropathy and physical functioning and how the longitudinal association between age and functioning differed by neuropathy status. Physical functioning was measured in 1996–2008 using timed performances on stair-climb, walking, sit-to-stand, and balance tests at the Michigan site of the Study of Women's Health Across the Nation, a population-based cohort study of women at midlife (n = 396). Peripheral neuropathy was measured in 2008 and defined as having an abnormal monofilament test result or 4 or more symptoms. We used linear mixed models to determine whether trajectories of physical functioning differed by prevalent neuropathy status. Overall, 27.8% of the women had neuropathy. Stair-climb time differed by neuropathy status (P = 0.04), and for every 1-year increase in age, women with neuropathy had a 1.82% (95% confidence interval: 1.42, 2.21) increase compared with a 0.95% (95% confidence interval: 0.71, 1.20) increase for women without neuropathy. Sit-to-stand time differed by neuropathy status (P = 0.01), but the rate of change did not differ. No differences between neuropathy groups were observed for the walk test. For some performance-based tasks, poor functioning was maintained or exacerbated for women who had prevalent neuropathy. Peripheral neuropathy may play a role in physical functioning limitations and future disability. PMID:23524038

Neurophysiological profile of peripheral neuropathy associated with childhood mitochondrial disease.

PubMed

Menezes, Manoj P; Rahman, Shamima; Bhattacharya, Kaustuv; Clark, Damian; Christodoulou, John; Ellaway, Carolyn; Farrar, Michelle; Pitt, Matthew; Sampaio, Hugo; Ware, Tyson L; Wedatilake, Yehani; Thorburn, David R; Ryan, Monique M; Ouvrier, Robert

2016-09-01

Peripheral nerve involvement is common in mitochondrial disease but often unrecognised due to the prominent central nervous system features. Identification of the underlying neuropathy may assist syndrome classification, targeted genetic testing and rehabilitative interventions. Clinical data and the results of nerve conduction studies were obtained retrospectively from the records of four tertiary children's hospital metabolic disease, neuromuscular or neurophysiology services. Nerve conductions studies were also performed prospectively on children attending a tertiary metabolic disease service. Results were classified and analysed according to the underlying genetic cause. Nerve conduction studies from 27 children with mitochondrial disease were included in the study (mitochondrial DNA (mtDNA) - 7, POLG - 7, SURF1 - 10, PDHc deficiency - 3). Four children with mtDNA mutations had a normal study while three had mild abnormalities in the form of an axonal sensorimotor neuropathy when not acutely unwell. One child with MELAS had a severe acute axonal motor neuropathy during an acute stroke-like episode that resolved over 12months. Five children with POLG mutations and disease onset beyond infancy had a sensory ataxic neuropathy with an onset in the second decade of life, while the two infants with POLG mutations had a demyelinating neuropathy. Seven of the 10 children with SURF1 mutations had a demyelinating neuropathy. All three children with PDHc deficiency had an axonal sensorimotor neuropathy. Unlike CMT, the neuropathy associated with mitochondrial disease was not length-dependent. This is the largest study to date of peripheral neuropathy in genetically- classified childhood mitochondrial disease. Characterising the underlying neuropathy may assist with the diagnosis of the mitochondrial syndrome and should be an integral part of the assessment of children with suspected mitochondrial disease. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society

Peripheral neuropathy may not be the only fundamental reason explaining increased sway in diabetic individuals.

PubMed

Bonnet, Cédrick T; Ray, Christopher

2011-08-01

Individuals with diabetic neuropathy sway more than control individuals while standing. This review specifically evaluated whether peripheral sensory neuropathy can be the only fundamental reason accounting for significant increased sway within this population. Twenty-six experimental articles were selected using MEDLINE and reference lists of relevant articles. The articles chosen investigated kinematic data of postural behaviour in controls and individuals with diabetic neuropathy during stance. Results of literature were compared with four expectations related to the peripheral sensory neuropathy fundamental hypothesis. Consistent with the peripheral sensory neuropathy hypothesis, the literature showed that individuals with diabetic neuropathy sway more than controls in quiet stance and even more so if their visual or vestibular systems were perturbed. Inconsistent with the hypothesis, individuals with diabetic neuropathy are more destabilised than controls in conditions altering sensation of the feet and legs (standing on a sway-referenced surface). The review showed that the peripheral sensory neuropathy hypothesis may not be the only fundamental cause accounting for significant increased postural sway in individuals with diabetic neuropathy. Visual impairments and changes in postural coordination may explain the divergence between expectations and results. In order to develop interventions aimed at improving postural control in individuals with diabetic neuropathy, scientific exploration of these new expectations should be detailed. Also at the practical level, the review discussed which additional sensory information - at the level of the hands and feet - may be more beneficial in individuals with diabetic neuropathy to reduce their postural sway. Copyright © 2011 Elsevier Ltd. All rights reserved.

Peripheral neuropathy following intentional inhalation of naphtha fumes.

PubMed Central

Tenenbein, M; deGroot, W; Rajani, K R

1984-01-01

Two adolescent native Canadians who presented with peripheral neuropathy secondary to the abuse of volatile hydrocarbons are described. They were initially thought to have been sniffing leaded gasoline fumes, but public health investigation revealed that they had been sniffing naphtha fumes. Naphtha contains a significant amount of n-hexane, a known inducer of neuropathy. Nerve conduction studies and nerve biopsy confirmed the diagnosis of naphtha abuse. These cases emphasize the need to specifically identify the formulation of hydrocarbons being abused. PMID:6093978

Presence of neuropathic pain may explain poor performances on olfactory testing in diabetes mellitus patients.

PubMed

Brady, Shauna; Lalli, Paul; Midha, Nisha; Chan, Ayechen; Garven, Alexandra; Chan, Cynthia; Toth, Cory

2013-07-01

Olfactory dysfunction in neurodegenerative conditions such as Parkinson's syndrome and Alzheimer's disease can hallmark disease onset. We hypothesized that patients with diabetes mellitus, a condition featuring peripheral and central neurodegeneration, would have decreased olfaction abilities. We examined participants with diabetic peripheral neuropathy, participants with diabetes without diabetic peripheral neuropathy, and control participants in blinded fashion using standardized Sniffin' Sticks. Diabetic peripheral neuropathy severity was quantified using the Utah Early Neuropathy Scale. Further subcategorization of diabetic peripheral neuropathy based on presence of neuropathic pain was performed with Douleur Neuropathique 4 Questionnaires. Participants with diabetes had decreased olfactory sensitivity, impaired olfactory discrimination abilities, and reduced odor identification skills when compared with controls. However, loss of olfaction ability was, at least partially, attributed to presence of neuropathic pain on subcategory assessment, although pain severity was not associated with dysfunction. Those participants with diabetes without diabetic peripheral neuropathy and those with diabetic peripheral neuropathy without neuropathic pain had similar olfactory function as controls in general. The presence of neuropathic pain, associated with limited attention and concentration, may explain at least a portion of the olfactory dysfunction witnessed in the diabetic patient population.

Incidence and relative risk of peripheral neuropathy in cancer patients treated with eribulin: a meta-analysis

PubMed Central

Peng, Ling; Hong, Yun; Ye, Xianghua; Shi, Peng; Zhang, Junyan; Wang, Yina; Zhao, Qiong

2017-01-01

Background Eribulin is a microtubule inhibitor, which is approved for the treatment of breast cancer. Peripheral neuropathy has been reported in the studies of eribulin, but the incidence and relative risk (RR) of eribulin-associated peripheral neuropathy varied greatly in cancer patients. The purpose of this meta-analysis was to determine the overall incidence and RR of eribulin-associated peripheral neuropathy in cancer patients. Materials and Methods Pubmed database and Embase and abstracts presented at the American Society of Clinical Oncology (ASCO) meetings were systematically reviewed for primary studies. Eligible studies included prospective clinical trials and expanded access programs of cancer patients treated with eribulin. Statistical analyses were performed to calculate the incidences, RRs, and 95% confidence intervals (CIs). Results Altogether, 4,849 patients from 19 clinical trials were selected for this meta-analysis. The incidences of all-grade and high-grade peripheral neuropathy were 27.5% (95% CI: 23.3–32.4%) and 4.7% (95% CI: 3.6–6.2%), respectively. The relative risks of peripheral neuropathy of eribulin compared to control were increased for all-grade (RR = 1.89, 95% CI: 1.10–3.25) but not statistically significant for high-grade (RR = 2.98, 95% CI: 0.71–12.42). Conclusions The use of eribulin is associated with an increased incidence of peripheral neuropathy. The RR is increased for all-grade peripheral neuropathy. PMID:29340112

Assessing the Risk for Peripheral Neuropathy in Patients Treated With Dronedarone Compared With That in Other Antiarrhythmics.

PubMed

Wu, Chuntao; Tcherny-Lessenot, Stephanie; Dai, Wanju; Wang, Yunxun; Kechemir, Hayet; Gandhi, Sampada; Lin, Stephen; Juhaeri, Juhaeri

2018-03-01

There are few data on the risk for peripheral neuropathy associated with dronedarone, a newer antiarrhythmic medicine. The objective of this study was to assess whether dronedarone is potentially associated with an increased risk for peripheral neuropathy compared with other antiarrhythmics, including amiodarone, sotalol, flecainide, and propafenone. The MarketScan database was used for identifying patients who were at least 18 years of age, had atrial fibrillation or flutter, and had not been diagnosed with peripheral neuropathy in the 180-day period prior to or on the date of the first prescription of an antiarrhythmic between July 20, 2009, and December 31, 2011. Peripheral neuropathy that occurred during the treatment period for a study drug was ascertained using ICD-9-CM diagnostic codes. For each antiarrhythmic, the incidence rate of peripheral neuropathy was calculated. The adjusted hazard ratio (aHR) for peripheral neuropathy for dronedarone compared with another antiarrhythmic was obtained, with control for age, sex, diabetes mellitus status, and the presence of other comorbidities. The study population included 106,933 patients treated with dronedarone (n = 12,989), amiodarone (n = 45,173), sotalol (n = 22,036), flecainide (n = 14,244), or propafenone (n = 12,491). The incidence rates (per 1000 person-years) of peripheral neuropathy were 1.33 for dronedarone, 2.38 for amiodarone, 1.20 for sotalol, 1.08 for flecainide, and 1.97 for propafenone. The aHRs for peripheral neuropathy for dronedarone relative to other drugs ranged from 0.53 (95% CI, 0.21-1.34) compared with propafenone, to 0.94 (95% CI, 0.38-2.30) compared with sotalol. A new-user analysis showed similar results. The risks for peripheral neuropathy were not significantly different between dronedarone and other antiarrhythmics. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Serum Uric Acid Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: a Systematic Review and Meta-analysis.

PubMed

Yu, Shuai; Chen, Ying; Hou, Xu; Xu, Donghua; Che, Kui; Li, Changgui; Yan, Shengli; Wang, Yangang; Wang, Bin

2016-03-01

Previous studies suggested a possible association between serum uric acid levels and peripheral neuropathy in patients with type 2 diabetes, but no definite evidence was available. A systematic review and meta-analysis of relevant studies were performed to comprehensively estimate the association. Pubmed, Web of Science, Embase, and China Biology Medicine (CBM) databases were searched for eligible studies. Study-specific data were combined using random-effect or fixed-effect models of meta-analysis according to between-study heterogeneity. Twelve studies were finally included into the meta-analysis, which involved a total of 1388 type 2 diabetic patients with peripheral neuropathy and 4746 patients without peripheral neuropathy. Meta-analysis showed that there were obvious increased serum uric acid levels in diabetic patients with peripheral neuropathy (weighted mean difference [WMD] = 50.03 μmol/L, 95% confidence interval [95%CI] 22.14-77.93, P = 0.0004). Hyperuricemia was also significantly associated with increased risk of peripheral neuropathy in patients with type 2 diabetes (risk ratio [RR] = 2.83, 95%CI 2.13-3.76, P < 0.00001). Meta-analysis of two studies with adjusted risk estimates showed that hyperuricemia was independently associated with increased risk of peripheral neuropathy in type 2 diabetic patients (RR = 1.95, 95%CI 1.23-3.11, P = 0.005). Type 2 diabetic patients with peripheral neuropathy have obvious increased serum uric acid levels, and hyperuricemia is associated with increased risk of peripheral neuropathy. Further prospective cohort studies are needed to validate the impact of serum uric acid levels on peripheral neuropathy risk.

Reversal of diabetic peripheral neuropathy and new wound incidence: the role of MIRE.

PubMed

Powell, Mark W; Carnegie, Dale E; Burke, Thomas J

2004-01-01

To determine if improved foot sensitivity to the Semmes-Weinstein 10-g (5.07) monofilament, originally impaired because of diabetic peripheral neuropathy, might be associated with a reduced incidence of new diabetic foot wounds. Retrospective cohort study using a health status questionnaire. Sixty-eight individuals over age 64 with diabetes, diabetic peripheral neuropathy, and loss of protective sensation who had clinically demonstrable increases in foot sensation to the Semmes-Weinstein monofilament after treatment with monochromatic near infrared photo energy. After reversal of diabetic peripheral neuropathy following treatment with monochromatic near infrared photo energy, only 1 of 68 patients developed a new diabetic foot wound, for an incidence of 1.5%. Comparatively, the incidence previously reported in the Medicare-aged population with diabetes was 7.3%. Improved foot sensitivity to the Semmes-Weinstein monofilament in patients previously suffering from loss of protective sensation due to diabetic neuropathy appears to be associated with a lower incidence of new diabetic foot ulcers when compared with the expected incidence in the Medicare-aged population with diabetes. Therapeutic interventions that effectively improve foot sensitivity that has been previously diminished due to diabetic peripheral neuropathy may substantially reduce the incidence of new foot wounds in the Medicare-aged population with diabetes.

Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

PubMed Central

Kerckhove, Nicolas; Collin, Aurore; Condé, Sakahlé; Chaleteix, Carine; Pezet, Denis; Balayssac, David

2017-01-01

Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a “stocking and glove” distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in

Peripheral neuropathy in HIV-infected and uninfected patients in Rakai, Uganda.

PubMed

Saylor, Deanna; Nakigozi, Gertrude; Nakasujja, Noeline; Robertson, Kevin; Gray, Ronald H; Wawer, Maria J; Sacktor, Ned

2017-08-01

To determine the prevalence, risk factors, and functional impairment associated with peripheral neuropathy in a prospective cohort of adults in rural Uganda. Eight hundred participants (400 HIV- and 400 antiretroviral-naive HIV+) in the Rakai Community Cohort Study underwent detailed neurologic evaluations including assessment of neuropathy symptoms, functional measures (Patient Assessment of Own Functioning Inventory and Karnofsky Performance Status scores), and neurologic evaluation by a trained medical officer. Neuropathy was defined as ≥1 subjective symptom and ≥1 sign of neuropathy on examination. Neuropathy risk factors were assessed using log binomial regression. Fifty-three percent of participants were men, with a mean (SD) age of 35 (8) years. Neuropathy was present in 13% of the cohort and was more common in HIV+ vs HIV- participants (19% vs 7%, p < 0.001). Older age (relative risk [RR] 1.04, 95% confidence interval [CI] 1.02-1.06), female sex (RR 1.49, 95% CI 1.04-2.15), HIV infection (RR 2.82, 95% CI 1.86-4.28), tobacco use (RR 1.59, 95% CI 1.02-2.48), and prior neurotoxic medication use (RR 2.08, 95% CI 1.07-4.05) were significant predictors of neuropathy in the overall cohort. Only older age was associated with neuropathy risk in the HIV+ (RR 1.03, 95% CI 1.01-1.05) and HIV- (RR 1.06, 95% CI 1.02-1.10) cohorts. Neuropathy was associated with impaired functional status on multiple measures across all participant groups. Peripheral neuropathy is relatively common and associated with impaired functional status among adults in rural Uganda. Older age, female sex, and HIV infection significantly increase the risk of neuropathy. Neuropathy may be an underrecognized but important condition in rural Uganda and warrants further study. © 2017 American Academy of Neurology.

Peripheral neuropathy in HIV-infected and uninfected patients in Rakai, Uganda

PubMed Central

Nakigozi, Gertrude; Nakasujja, Noeline; Robertson, Kevin; Gray, Ronald H.; Wawer, Maria J.; Sacktor, Ned

2017-01-01

Objective: To determine the prevalence, risk factors, and functional impairment associated with peripheral neuropathy in a prospective cohort of adults in rural Uganda. Methods: Eight hundred participants (400 HIV− and 400 antiretroviral-naive HIV+) in the Rakai Community Cohort Study underwent detailed neurologic evaluations including assessment of neuropathy symptoms, functional measures (Patient Assessment of Own Functioning Inventory and Karnofsky Performance Status scores), and neurologic evaluation by a trained medical officer. Neuropathy was defined as ≥1 subjective symptom and ≥1 sign of neuropathy on examination. Neuropathy risk factors were assessed using log binomial regression. Results: Fifty-three percent of participants were men, with a mean (SD) age of 35 (8) years. Neuropathy was present in 13% of the cohort and was more common in HIV+ vs HIV− participants (19% vs 7%, p < 0.001). Older age (relative risk [RR] 1.04, 95% confidence interval [CI] 1.02–1.06), female sex (RR 1.49, 95% CI 1.04–2.15), HIV infection (RR 2.82, 95% CI 1.86–4.28), tobacco use (RR 1.59, 95% CI 1.02–2.48), and prior neurotoxic medication use (RR 2.08, 95% CI 1.07–4.05) were significant predictors of neuropathy in the overall cohort. Only older age was associated with neuropathy risk in the HIV+ (RR 1.03, 95% CI 1.01–1.05) and HIV− (RR 1.06, 95% CI 1.02–1.10) cohorts. Neuropathy was associated with impaired functional status on multiple measures across all participant groups. Conclusions: Peripheral neuropathy is relatively common and associated with impaired functional status among adults in rural Uganda. Older age, female sex, and HIV infection significantly increase the risk of neuropathy. Neuropathy may be an underrecognized but important condition in rural Uganda and warrants further study. PMID:28679596

Economic evaluation of duloxetine as a first-line treatment for painful diabetic peripheral neuropathy in Mexico.

PubMed

Carlos, Fernando; Ramírez-Gámez, Jocelyn; Dueñas, Héctor; Galindo-Suárez, Rosa María; Ramos, Elisa

2012-01-01

To perform an economic evaluation of duloxetine, pregabalin, and both branded and generic gabapentin for managing pain in patients with painful diabetic peripheral neuropathy (PDPN) in Mexico. The analysis was conducted using a 3-month decision model, which compares duloxetine 60 mg once daily (DUL), pregabalin 150 mg twice daily (PGB), and gabapentin 600 mg three-times daily (GBP) for PDPN patients with moderate-to-severe pain. A systematic review was performed and placebo-adjusted risk ratios for achieving good pain relief (GPR), adverse events (AE), and withdrawal owing to intolerable AE were calculated. Direct medical costs included drug acquisition and additional visits due to lack of efficacy (poor pain relief) or intolerable AE. Unit costs were taken from local sources. Adherence rates were used to estimate the expected drug costs. All costs are expressed in 2010 Mexican Pesos (MXN). Utility values drawn from published literature were applied to health states. The proportion of patients with GPR and quality-adjusted life years (QALY) were assessed. Branded-GBP was dominated by all the other options. PGB was more costly and less effective than DUL. Compared with branded-GBP and PGB, DUL led to savings of 1.01 and 1.74 million MXN (per 1000 patients). The incremental cost per QALY gained with DUL used instead of generic-GBP was $102 433 MXN. This amount is slightly lower than the estimated gross domestic product per capita in Mexico for 2010. During a second-order Monte Carlo simulation, DUL had the highest probability of being cost-effective (61%), followed by generic-GBP (25%) and PGB (14%). Study limitations include a short timeframe and using data from different dosage schemes for GBP and PGB. This study suggests that DUL provides overall savings and better health outcomes compared with branded-GBP and PGB. Administering DUL rather than generic-GBP is a cost-effective intervention to manage PDPN in Mexico.

[Toronto clinical scoring system in diabetic peripheral neuropathy].

PubMed

Liu, Feng; Mao, Ji-Ping; Yan, Xiang

2008-12-01

To evaluate the application value of Toronto clinical scoring system (TCSS) and its grading of neuropathy for diabetic peripheral neuropathy (DPN), and to explore the relationship between TCSS grading of neuropathy and the grading of diabetic nephropathy and diabetic retinopathy. A total of 209 patients of Type 2 diabtes (T2DM) underwent TCSS. Taking electrophysiological examination as a gold standard for diagnosing DPN, We compared the results of TCSS score > or = 6 with electrophysiological examination, and tried to select the optimal cut-off points of TCSS. The corresponding accuracy, sensitivity, and specificity of TCSS score > or = 6 were 76.6%, 77.2%, and 75.6%, respectively.The Youden index and Kappa were 0.53 and 0.52, which implied TCSS score > or = 6 had a moderate consistency with electrophysiological examination. There was a linear positive correlation between TCSS grading of neuropathy and the grading of diabetic nephropathy and diabetic retinopathy (P<0.05). The optimal cut-off point was 5 or 6 among these patients. TCSS is reliable in diagnosing DPN and its grading of neuropathy has clinical value.

Diabetes, peripheral neuropathy, and lower-extremity function.

PubMed

Chiles, Nancy S; Phillips, Caroline L; Volpato, Stefano; Bandinelli, Stefania; Ferrucci, Luigi; Guralnik, Jack M; Patel, Kushang V

2014-01-01

Diabetes among older adults causes many complications, including decreased lower-extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine the following: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship. This study included 983 participants, age 65 years and older from the InCHIANTI study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0 to 12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cutpoints of PNF tests were used to create a neuropathy score from 0 to 5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations. One hundred twenty-six (12.8%) participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β=-0.99; p<0.01), decreased walking speed (β=-0.1m/s; p<0.01), decreased nerve conduction velocity (β=-1.7m/s; p<0.01), and increased neuropathy (β=0.25; p<0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF. © 2014.

Diabetes, Peripheral Neuropathy, and Lower Extremity Function

PubMed Central

Chiles, Nancy S.; Phillips, Caroline L.; Volpato, Stefano; Bandinelli, Stefania; Ferrucci, Luigi; Guralnik, Jack M.; Patel, Kushang V.

2014-01-01

Objective Diabetes among older adults causes many complications, including decreased lower extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship. Research Design and Methods This study included 983 participants, age 65 and older from the InCHIANTI Study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0-12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cut-points of PNF tests were used to create a neuropathy score from 0-5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations. Results and Conclusion 12.8% (n=126) of participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β= −0.99; p< 0.01), decreased walking speed (β= −0.1m/s; p< 0.01), decreased nerve conduction velocity (β= −1.7m/s; p< 0.01), and increased neuropathy (β= 0.25; p< 0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF. PMID:24120281

Alcoholic neuropathy: possible mechanisms and future treatment possibilities

PubMed Central

Chopra, Kanwaljit; Tiwari, Vinod

2012-01-01

Chronic alcohol consumption produces painful peripheral neuropathy for which there is no reliable successful therapy, mainly due to lack of understanding of its pathobiology. Alcoholic neuropathy involves coasting caused by damage to nerves that results from long term excessive drinking of alcohol and is characterized by spontaneous burning pain, hyperalgesia and allodynia. The mechanism behind alcoholic neuropathy is not well understood, but several explanations have been proposed. These include activation of spinal cord microglia after chronic alcohol consumption, oxidative stress leading to free radical damage to nerves, activation of mGlu5 receptors in the spinal cord and activation of the sympathoadrenal and hypothalamo-pituitary-adrenal (HPA) axis. Nutritional deficiency (especially thiamine deficiency) and/or the direct toxic effect of alcohol or both have also been implicated in alcohol-induced neuropathic pain. Treatment is directed towards halting further damage to the peripheral nerves and restoring their normal functioning. This can be achieved by alcohol abstinence and a nutritionally balanced diet supplemented by all B vitamins. However, in the setting of ongoing alcohol use, vitamin supplementation alone has not been convincingly shown to be sufficient for improvement in most patients. The present review is focused around the multiple pathways involved in the development of peripheral neuropathy associated with chronic alcohol intake and the different therapeutic agents which may find a place in the therapeutic armamentarium for both prevention and management of alcoholic neuropathy. PMID:21988193

Clinical efficacy of aconitum-containing traditional Chinese medicine for diabetic peripheral neuropathic pain.

PubMed

Feng, Ling; Liu, Wen-Ke; Deng, Lan; Tian, Jia-Xing; Tong, Xiao-Lin

2014-01-01

Diabetic peripheral neuropathy is a common chronic complication of diabetes. Routine clinical management uses analgesics to relieve pain in combination with drugs for nerve repair. The drugs are often not effective for the severe pain cases, and these western medications also have side effects. We report a more effective treatment of diabetic peripheral neuropathic pain using a high dose of a traditional Chinese medicine, aconitum (including both Radix aconite preparata and Radix aconite kusnezoffii), in combination with Huangqi Guizhi Wuwu Tang (i.e., astragalus, cassia twig, white peony root, and spatholobi). In order to achieve stronger analgesic effects, we increased the clinical dosage of aconitum from 15 to 120 g. The aconitum was boiled for 6-8 hours, and licorice was also used to reduce potential toxicities of aconitum. In the four reported cases, the patients' neuropathic pain was remarkably reduced and the EMG profile was also improved with this treatment regimen. Adverse reactions were not observed during the therapy. Thus, aconitum represents a promising and safe treatment for the well-being of patients and their diabetic peripheral neuropathic pain. Future controlled clinical trials using traditional Chinese medicines containing aconitum in treating the neuropathic pain are warranted.

Genetics Home Reference: paroxysmal extreme pain disorder

MedlinePlus

... extreme pain disorder is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which ... Page National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy Information Page Educational Resources (6 links) Disease InfoSearch: ...

Genetics Home Reference: congenital insensitivity to pain

MedlinePlus

... insensitivity to pain is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which ... link) National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy Information Page Educational Resources (5 links) Disease InfoSearch: ...

Novel insights on diagnosis, cause and treatment of diabetic neuropathy: focus on painful diabetic neuropathy

PubMed Central

Tavakoli, Mitra; Asghar, Omar; Alam, Uazman; Petropoulos, Ioannis N.; Fadavi, Hassan; Malik, Rayaz A.

2010-01-01

Diabetic neuropathy is common, under or misdiagnosed, and causes substantial morbidity with increased mortality. Defining and developing sensitive diagnostic tests for diabetic neuropathy is not only key to implementing earlier interventions but also to ensure that the most appropriate endpoints are employed in clinical intervention trials. This is critical as many potentially effective therapies may never progress to the clinic, not due to a lack of therapeutic effect, but because the endpoints were not sufficiently sensitive or robust to identify benefit. Apart from improving glycaemic control, there is no licensed treatment for diabetic neuropathy, however, a number of pathogenetic pathways remain under active study. Painful diabetic neuropathy is a cause of considerable morbidity and whilst many pharmacological and nonpharmacological interventions are currently used, only two are approved by the US Food and Drug Administration. We address the important issue of the ‘placebo effect’ and also consider potential new pharmacological therapies as well as nonpharmacological interventions in the treatment of painful diabetic neuropathy. PMID:23148152

Charcot Marie Tooth 2B Peripheral Sensory Neuropathy: How Rab7 Mutations Impact NGF Signaling?

PubMed

Liu, Harry; Wu, Chengbiao

2017-02-04

Charcot-Marie-Tooth 2B peripheral sensory neuropathy (CMT2B) is a debilitating autosomal dominant hereditary sensory neuropathy. Patients with this disease lose pain sensation and frequently need amputation. Axonal dysfunction and degeneration of peripheral sensory neurons is a major clinical manifestation of CMT2B. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M) in Rab7 GTPase. Strong evidence suggests that the Rab7 mutation(s) enhances the cellular levels of activated Rab7 proteins, thus resulting in increased lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor (NGF) in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A "gain of toxicity" model has, thus, been proposed based on these observations. However, studies of fly photo-sensory neurons indicate that the Rab7 mutation(s) causes a "loss of function", resulting in haploinsufficiency. In the review, we summarize experimental evidence for both hypotheses. We argue that better models (rodent animals and human neurons) of CMT2B are needed to precisely define the disease mechanisms.

Severe peripheral neuropathy and elevated plantar pressures causing foot ulceration in pituitary gigantism.

PubMed

Jennings, A M; Robinson, A; Kandler, R H; Betts, R P; Ryder, R E; Cullen, D R

1993-07-01

We report two patients with treated pituitary gigantism and peripheral neuropathy, one of whom has chronic foot ulceration. Detailed neurophysiological assessment was performed on both patients. The patient with foot ulceration had clinical and neurophysiological evidence of severe neuropathy, whereas the patient without ulceration had only neurophysiological abnormalities. The sweating response to acetylcholine was markedly impaired in the feet of both patients, suggesting pedal autonomic denervation. Neither patient had evidence of diabetes mellitus and detailed investigation failed to reveal an alternative cause of peripheral neuropathy. Optical pedobarography revealed abnormally high pressure (> 10 kg/cm2) under the metatarsal heads of both patients, one such area coinciding with the area of ulceration. Thus in pituitary gigantism elevated plantar pressures may contribute to the development of foot ulceration when severe peripheral neuropathy is present. Furthermore, as in diabetes mellitus, impaired sweating may also increase the risk of ulceration as the resultant dry skin may develop fissures.

Altered joint moment strategy during stair walking in diabetes patients with and without peripheral neuropathy.

PubMed

Brown, Steven J; Handsaker, Joseph C; Maganaris, Constantinos N; Bowling, Frank L; Boulton, Andrew J M; Reeves, Neil D

2016-05-01

To investigate lower limb biomechanical strategy during stair walking in patients with diabetes and patients with diabetic peripheral neuropathy, a population known to exhibit lower limb muscular weakness. The peak lower limb joint moments of twenty-two patients with diabetic peripheral neuropathy and thirty-nine patients with diabetes and no neuropathy were compared during ascent and descent of a staircase to thirty-two healthy controls. Fifty-nine of the ninety-four participants also performed assessment of their maximum isokinetic ankle and knee joint moment (muscle strength) to assess the level of peak joint moments during the stair task relative to their maximal joint moment-generating capabilities (operating strengths). Both patient groups ascended and descended stairs slower than controls (p<0.05). Peak joint moments in patients with diabetic peripheral neuropathy were lower (p<0.05) at the ankle and knee during stair ascent, and knee only during stair descent compared to controls. Ankle and knee muscle strength values were lower (p<0.05) in patients with diabetic peripheral neuropathy compared to controls, and lower at knee only in patients without neuropathy. Operating strengths were higher (p<0.05) at the ankle and knee in patients with neuropathy during stair descent compared to the controls, but not during stair ascent. Patients with diabetic peripheral neuropathy walk slower to alter gait strategy during stair walking and account for lower-limb muscular weakness, but still exhibit heightened operating strengths during stair descent, which may impact upon fatigue and the ability to recover a safe stance following postural instability. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Celiac Disease Presenting with Peripheral Neuropathy in Children: A Case Report.

PubMed

Pacitto, Alessandra; Paglino, Alessandra; Di Genova, Lorenza; Leonardi, Alberto; Farinelli, Edoardo; Principi, Nicola; di Cara, Giuseppe; Esposito, Susanna

2017-07-14

Background: Clinically relevant neurological manifestations in children with celiac disease (CD) are unusual, especially when they are considered as signs of the onset of the disease. In this paper, a case of Guillain-Barrè syndrome (GBS) as the first manifestation of CD in a 23-month-old child is reported. Case presentation: We describe a case of CD onset with peripheral neuropathy in a 23-month-old Bulgarian boy presenting with a sudden refusal to walk and absence of deep tendon reflexes in both lower limbs. Neurological symptoms were preceded by two months of gastrointestinal symptoms such as vomiting, abdominal distention, and clear signs of malnutrition and weight loss. When we evaluated the child six months after the onset of the symptoms, clinical and laboratory findings showed clear signs of peripheral neuropathy associated with malnutrition. Serum deamidated gliadin and tissue transglutaminase antibodies were therefore measured. The anti-gliadin levels were more than sixteen times higher than normal and the IgA anti-transglutaminase levels were four times higher than normal. Anti-endomysium antibodies were positive, and human leukocyte antigens (HLA) II typing confirmed a genetic predisposition to CD (DQ2 positive and DQ8 negative). Given the association between the clinical evidence of the disease and the results of the celiac screening tests, a diagnosis of CD was made without biopsy confirmation of the enteropathy. The child began a restricted gluten-free diet that led to complete recovery of the peripheral neuropathy, walking, reflexes, and overall improvement after three months on the diet. Conclusion: Our case underlines the rare but possible associations between CD and peripheral neuropathy in children as an onset symptom, even in the absence of gastrointestinal manifestations, thus suggesting that CD should always be considered in the differential diagnosis of peripheral neuropathy in children. A good knowledge of the extra

Pregabalin versus gabapentin in the management of peripheral neuropathic pain associated with post-herpetic neuralgia and diabetic neuropathy: a cost effectiveness analysis for the Greek healthcare setting

PubMed Central

2013-01-01

Background The anticonvulsants pregabalin and gabapentin are both indicated for the treatment of peripheral neuropathic pain. The decision on which treatment provides the best alternative, should take into account all aspects of costs and outcomes associated with the two therapeutic options. The objective of this study was to examine the cost – effectiveness of the two agents in the management of patients with painful diabetic neuropathy or post – herpetic neuralgia, under the third party payer perspective in Greece. Methods The analysis was based on a dynamic simulation model which estimated and compared the costs and outcomes of pregabalin and gabapentin in a hypothetical cohort of 1,000 patients suffering from painful Diabetic Peripheral Neuropathy (DPN) or Post-Herpetic Neuralgia (PHN). In the model, each patient was randomly allocated an average pretreatment pain score, measured using an eleven-point visual analogue scale (0 – 10) and was “run through” the model, simulating their daily pain intensity and allowing for stochastic calculation of outcomes, taking into account medical interventions and the effectiveness of each treatment. Results Pregabalin demonstrated a reduction in days with moderate to severe pain when compared to gabapentin. During the 12 weeks the pregabalin arm demonstrated a 0.1178 (SE 0.0002) QALY gain, which proved to be 0.0063 (SE 0.0003) higher than that in the gabapentin arm. The mean medication cost per patient was higher for the pregabalin arm when compared to the gabapentin arm (i.e. €134.40) over the 12 week treatment period. However, this higher cost was partially offset by the reduced direct medical costs (i.e. the cost of specialist visits, the cost of diagnostic tests and the other applied interventions). Comparing costs with respective outcomes, the ICERs for pregabalin versus gabapentin were €13 (95%CI: 8 – 18) per additional day with no or mild pain and €19,320 (95%CI: 11,743 – 26,755) per QALY gained

A Systematic Review of Experimental and Clinical Acupuncture in Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Franconi, Giovanna; Schröder, Sven; Marchetti, Paolo; Robinson, Nicola

2013-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that can be very disabling and can limit or delay the dose of chemotherapy that can be administered. Acupuncture may be effective for treating peripheral neuropathy. The aim of this study was to review the available literature on the use of acupuncture for CIPN. The systematic literature search was performed using MEDLINE, Google Scholar, Cochrane Database, CINHAL, and ISI Proceedings. Hand searching was conducted, and consensus was reached on all extracted data. Only papers in the English language were included, irrespective of study design. From 3989 retrieved papers, 8 relevant papers were identified. One was an experimental study which showed that electroacupuncture suppressed CIPN pain in rats. In addition, there were 7 very heterogeneous clinical studies, 1 controlled randomised study using auricular acupuncture, 2 randomized controlled studies using somatic acupuncture, and 3 case series/case reports which suggested a positive effect of acupuncture in CIPN. Conclusions. Only one controlled randomised study demonstrated that acupuncture may be beneficial for CIPN. All the clinical studies reviewed had important methodological limitations. Further studies with robust methodology are needed to demonstrate the role of acupuncture for treating CIPN resulting from cancer treatment. PMID:23983788

Clinical effectiveness of low-level laser treatment on peripheral somatosensory neuropathy.

PubMed

Fallah, Alireza; Mirzaei, Alireza; Gutknecht, Norbert; Demneh, Amir Saberi

2017-04-01

Peripheral sensory neuropathy treatment is one of the common treatment problems and causes morbidity and mortality in people suffering from that. Although treatment depends on the underlying cause of the condition, nevertheless, in some cases, there is no cure for it, and it requires palliative and symptomatic treatment. In laboratory studies, low-level laser has been effective in the nerves protection and restoration. The aim of this article is to investigate the clinical efficacy of low-level laser on improvement of the peripheral somatosensory neuropathy. Search in the articles published up to 30 October 2015 (full text and abstracts) in databases PubMed (Medline), Cochrane library, Physiotherapy Evidence Database was performed. The studies of low-level laser trials on patients with peripheral neuropathy were carried out and evaluated in terms of the exclusion criteria. There are 35 articles among which 10 articles had the intended and required criteria. 1, 3, and 6 articles study the patients with diabetes, neuropathy caused by trauma, and carpal tunnel syndrome, respectively. In six studies, laser led to a reduction in sensory impairment and improvement of the physiological function of the sensory nerves. In these articles, lasers (Diode, GaAlAs, He-Ne) had wavelength range 660-860 nm, radiation power 20-250 mW, energy density 0.45-70 J/cm 2 . The intervention sessions range was 6-21 times and patient follow-up was 0-6 months. According to the results of these studies, low-level laser therapy can improve sensory function in patients with peripheral somatosensory neuropathy, although little research have not been done, laser treatment regimens are varied and do not recommend a specific treatment protocol. It seems it requires more research to sum up better, particularly in relation to diabetes.

Downregulation of adenosine and adenosine 1 receptor contributes to neuropathic pain in resiniferatoxin neuropathy.

PubMed

Kan, Hung-Wei; Chang, Chin-Hong; Lin, Chih-Lung; Lee, Yi-Chen; Hsieh, Sung-Tsang; Hsieh, Yu-Lin

2018-04-16

The neurochemical effects of adenosine signaling in small-fiber neuropathy leading to neuropathic pain are yet to be explored in a direct manner. This study examined this system at the level of ligand (via the ectonucleotidase activity of prostatic acid phosphatase, PAP) and adenosine A1 receptors (A1Rs) in resiniferatoxin (RTX) neuropathy, a peripheral neurodegenerative disorder which specifically affects nociceptive nerves expressing transient receptor potential vanilloid type 1 (TRPV1). We conducted immunohistochemistry on dorsal root ganglion neurons (DRG), high-performance liquid chromatography (HPLC) for functional assays, and pharmacological interventions to alter PAP and A1Rs in mice with RTX neuropathy. In DRG of RTX neuropathy, PAP(+) neurons were reduced compared with vehicle-treated mice (P = 0.002) . Functionally, PAP ectonucleotidase activity was consequently reduced (i.e., the content of adenosine in DRG, P = 0.012). PAP(+) neuronal density was correlated with the degree of mechanical allodynia, which was reversed by intrathecal lumbar puncture (i.t.) injection of recombinant PAP with a dose-dependent effect. Furthermore, A1Rs were downregulated (P = 0.002), and this downregulation was colocalized with the TRPV1 receptor (31.0% ± 2.8%). Mechanical allodynia was attenuated in a dose-dependent response by i.t. injection of the A1R ligand, adenosine; however, no analgesia was evident when an exogenous adenosine was blocked by A1R antagonist. This study demonstrated dual mechanisms of neuropathic pain in TRPV1-induced neuropathy, involving a reduced adenosine system at both the ligand (adenosine) and receptor (A1Rs) levels.

"Mitochondrial neuropathies": A survey from the large cohort of the Italian Network.

PubMed

Mancuso, Michelangelo; Orsucci, Daniele; Angelini, Corrado; Bertini, Enrico; Carelli, Valerio; Comi, Giacomo Pietro; Federico, Antonio; Minetti, Carlo; Moggio, Maurizio; Mongini, Tiziana; Tonin, Paola; Toscano, Antonio; Bruno, Claudio; Ienco, Elena Caldarazzo; Filosto, Massimiliano; Lamperti, Costanza; Diodato, Daria; Moroni, Isabella; Musumeci, Olimpia; Pegoraro, Elena; Spinazzi, Marco; Ahmed, Naghia; Sciacco, Monica; Vercelli, Liliana; Ardissone, Anna; Zeviani, Massimo; Siciliano, Gabriele

2016-01-01

Involvement of the peripheral nervous system in mitochondrial disorders has been previously reported. However, the prevalence of peripheral neuropathy in mitochondrial disorders is still unclear. Based on the large database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", we reviewed the clinical data of 1200 patients, with special regard to peripheral neuropathy (mean age at onset 24.3 ± 20.1 years; age at last evaluation 39.8 ± 22.3 years; females 52.7%; childhood onset [before age 16 years] 43.1%). Peripheral neuropathy was present in 143/1156 patients (12.4%), being one of the ten most common signs and symptoms. POLG mutations cause a potentially painful, axonal/mixed, mainly sensory polyneuropathy; TYMP mutations lead to a demyelinating sensory-motor polyneuropathy; SURF1 mutations are associated with a demyelinating/mixed sensory-motor polyneuropathy. The only mtDNA mutation consistently associated with peripheral neuropathy (although less severely than in the above-considered nuclear genes) was the m.8993T > G (or the rarer T > C) changes, which lead to an axonal, mainly sensory polyneuropathy. In conclusion, peripheral neuropathy is one of the most common features of a mitochondrial disorder, and may negatively impact on the quality of life of these patients. Furthermore, the presence or absence of peripheral neuropathy, as well as its specific forms and the association with neuropathic pain (indicative of a POLG-associated disease) can guide the molecular analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Peripheral neuropathy in military aircraft maintenance workers in Australia.

PubMed

Guest, Maya; Attia, John R; D'este, Catherine A; Boggess, May M; Brown, Anthony M; Gibson, Richard E; Tavener, Meredith A; Ross, James; Gardner, Ian; Harrex, Warren

2011-04-01

This study aimed to examine possible persisting peripheral neuropathy in a group who undertook fuel tank repairs on F-111 aircraft, relative to two contemporaneous comparison groups. Vibration perception threshold (VPT) was tested using biothesiometry in 614 exposed personnel, compared with two unexposed groups (513 technical trades and 403 nontrades). Regression modeling was used to examine associations, adjusting for possible confounders. We observed that 26% of participants had chronic persistent increased VPT in the great toe. In contrast, statistically significant higher VPT of the great toe was observed in the comparison groups; however, the effect was small, about 1/4 the magnitude of diabetes. Age, height, and diabetes were all significant and strong predictors in most models. This study highlights chronic persisting peripheral neuropathy in a population of aircraft maintainers.

Metronidazole: newly recognized cause of autonomic neuropathy.

PubMed

Hobson-Webb, Lisa D; Roach, E Steve; Donofrio, Peter D

2006-05-01

Metronidazole is a commonly used antibiotic prescribed for the treatment of anaerobic and protozoal infections of the gastrointestinal and genitourinary tracts. It is associated with numerous neurologic complications, including peripheral neuropathy. Neuropathy is typically detected in patients on chronic therapy, although it has been documented in those taking large doses for acute infections. Numerous case reports have been published describing motor and sensory neuropathy, yet autonomic neuropathy has not been described with metronidazole use. A previously healthy 15-year-old girl presented with complaints of burning pain in her feet following a short course of metronidazole for vaginitis. She could obtain pain relief only by submerging her feet in ice water. Examination revealed cold and swollen lower extremities that became erythematous and very warm when removed from the ice water. Temperature perception was reduced to the upper third of the shin bilaterally. Deep tendon reflexes and strength were preserved. Nerve conduction studies demonstrated a peripheral neuropathy manifested by reduced sensory nerve and compound muscle action potentials. Reproducible sympathetic skin potential responses could not be obtained in the hand and foot, providing evidence of a concurrent autonomic neuropathy. A thorough evaluation revealed no other cause for her condition. Repeated nerve conduction studies and sympathetic skin potentials returned to normal over the course of 6 months, paralleling the patient's clinical improvement. Metronidazole is a potential cause of reversible autonomic neuropathy.

Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency.

PubMed

Taylor, Sean W; Laughlin, Ruple S; Kumar, Neeraj; Goodman, Brent; Klein, Christopher J; Dyck, Peter J; Dyck, P James B

2017-10-01

Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised. To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy. Patients with simultaneous copper deficiency (<0.78 μg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified. 34 patients were identified (median age 55 years, range 36-78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0-0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation. An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Vincristine-induced peripheral neuropathy in pediatric cancer patients

PubMed Central

Mora, Erika; Smith, Ellen M Lavoie; Donohoe, Clare; Hertz, Daniel L

2016-01-01

Vincristine is a chemotherapeutic agent that is a component of many combination regimens for a variety of malignancies, including several common pediatric tumors. Vincristine treatment is limited by a progressive sensorimotor peripheral neuropathy. Vincristine-induced peripheral neuropathy (VIPN) is particularly challenging to detect and monitor in pediatric patients, in whom the side effect can diminish long term quality of life. This review summarizes the current state of knowledge regarding VIPN, focusing on its description, assessment, prediction, prevention, and treatment. Significant progress has been made in our knowledge about VIPN incidence and progression, and tools have been developed that enable clinicians to reliably measure VIPN in pediatric patients. Despite these successes, little progress has been made in identifying clinically useful predictors of VIPN or in developing effective approaches for VIPN prevention or treatment in either pediatric or adult patients. Further research is needed to predict, prevent, and treat VIPN to maximize therapeutic benefit and avoid unnecessary toxicity from vincristine treatment. PMID:27904761

Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN)

PubMed Central

Canta, Annalisa; Pozzi, Eleonora; Carozzi, Valentina Alda

2015-01-01

The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN). This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy. PMID:29056658

High-tone external muscle stimulation in end-stage renal disease: effects on symptomatic diabetic and uremic peripheral neuropathy.

PubMed

Klassen, A; Di Iorio, B; Guastaferro, P; Bahner, U; Heidland, A; De Santo, N

2008-01-01

Pain and peripheral neuropathy are frequent complications of end-stage renal disease (ESRD). Because drug treatment is associated with numerous side effects and is largely ineffective in many maintenance hemodialysis (MHD) patients, nonpharmacologic strategies such as electrotherapy are a potential recourse. Among various forms of electrostimulation, high-tone external muscle stimulation (HTEMS) is a promising alternative treatment for symptomatic diabetic peripheral polyneuropathy (PPN), as demonstrated in a short-term study. Based on these novel findings, we performed a prospective, nonrandomized, pilot trial in MHD patients to determine (1) whether HTEMS is also effective in treating diabetic PPN in the uremic state, and (2) whether uremic PPN is similarly modulated. In total, 40 MHD patients diagnosed with symptomatic PPN (25 with diabetic and 15 with uremic PPN) were enrolled. Both lower extremities were treated intradialytically with HTEMS for 1 hour, three times a week. Initially, a subgroup of 12 patients was followed for 4 weeks, and a further 28 patients for 12 weeks. The patients' degree of neuropathy was graded at baseline before HTEMS and after 1 and 3 months, respectively. Five neuropathic symptoms (tingling, burning, pain, numbness, and numbness in painful areas) as well as sleep disturbances were measured, using the 10-point Neuropathic Pain Scale of Galer and Jensen (Neurology 48:332-338, 1997). A positive response was defined as the improvement of one symptom or more, by at least 3 points. Other parameters included blood pressure, heart rate, dry body weight, and a routine laboratory investigation. The HTEMS led to a significant improvement in all five neuropathic symptoms, and to a significant reduction in sleep disturbances for both diabetic and uremic PPN. The response was independent of the patient's age, with a responder rate of 73%. The improvement of neuropathy was time-dependent, with the best results achieved after 3 months of treatment

Duloxetine, Pregabalin, and Duloxetine Plus Gabapentin for Diabetic Peripheral Neuropathic Pain Management in Patients With Inadequate Pain Response to Gabapentin: An Open-Label, Randomized, Noninferiority Comparison

PubMed Central

Tanenberg, Robert J.; Irving, Gordon A.; Risser, Richard C.; Ahl, Jonna; Robinson, Michael J.; Skljarevski, Vladimir; Malcolm, Sandra K.

2011-01-01

OBJECTIVE: To determine whether duloxetine is noninferior to (as good as) pregabalin in the treatment of pain associated with diabetic peripheral neuropathy. PATIENTS AND METHODS: We performed a 12-week, open-label study of patients with diabetic peripheral neuropathic pain who had been treated with gabapentin (≥900 mg/d) and had an inadequate response (defined as a daily pain score of ≥4 on a numerical rating scale [0-10 points]). The first patient was enrolled on September 28, 2006, and the last patient visit occurred on August 26, 2009. Patients were randomized to duloxetine monotherapy (n=138), pregabalin monotherapy (n=134), or a combination of duloxetine and gabapentin (n=135). The primary objective was a noninferiority comparison between duloxetine and pregabalin on improvement in the weekly mean of the diary-based daily pain score (0- to 10-point scale) at end point. Noninferiority would be declared if the mean improvement for duloxetine was no worse than the mean improvement for pregabalin, within statistical variability, by a margin of –0.8 unit. RESULTS: The mean change in the pain rating at end point was –2.6 for duloxetine and –2.1 for pregabalin. The 97.5% lower confidence limit was a –0.05 difference in means, establishing noninferiority. As to adverse effects, nausea, insomnia, hyperhidrosis, and decreased appetite were more frequent with duloxetine than pregabalin; insomnia, more frequent with duloxetine than duloxetine plus gabapentin; peripheral edema, more frequent with pregabalin than with duloxetine; and nausea, hyperhidrosis, decreased appetite, and vomiting, more frequent with duloxetine plus gabapentin than with pregabalin. CONCLUSION: Duloxetine was noninferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy who had an inadequate pain response to gabapentin. Trial Registration: clinicaltrials.gov Identifier: NCT00385671 PMID:21719618

Retinal Tissue Thickness is Reduced in Diabetic Peripheral Neuropathy.

PubMed

Srinivasan, Sangeetha; Pritchard, Nicola; Vagenas, Dimitrios; Edwards, Katie; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2016-10-01

To investigate the relationship between diabetic peripheral neuropathy (DPN) and retinal tissue thickness. Full retinal thickness in the central retinal, parafoveal, and perifoveal zones and thickness of the ganglion cell complex and retinal nerve fiber layer (RNFL) were assessed in 193 individuals (84 with type 1 diabetes, 67 with type 2 diabetes, and 42 healthy controls) using spectral domain optical coherence tomography. Among those with diabetes, 44 had neuropathy defined using a modified neuropathy disability score recorded on a 0-10 scale. Multiple regression analysis was performed to investigate the relationship between diabetic neuropathy and retinal tissue thickness, adjusted for the presence of diabetic retinopathy (DR), age, sex, duration of diabetes, and HbA 1c levels. In individuals with diabetes, perifoveal thickness was inversely related to the severity of neuropathy (p < 0.05), when adjusted for age, sex, duration of diabetes, and HbA 1c levels. DR was associated with reduced thickness in parafovea (p < 0.01). The RNFL was thinner in individuals with greater degrees of neuropathy (p < 0.04). DPN is associated with structural compromise involving several retinal layers. This compromise may represent a threat to visual integrity and therefore warrants examination of functional correlates.

A longitudinal study of painless and painful intercostobrachial neuropathy after breast cancer surgery.

PubMed

La Cesa, S; Sammartino, P; Mollica, C; Cascialli, G; Cruccu, G; Truini, A; Framarino-Dei-Malatesta, M

2018-04-29

Intercostobrachial neuropathy, often resulting in neuropathic pain, is a common complication of breast cancer surgery. In this 1-year longitudinal study, we aimed at seeking information on the frequency, clinical features, and course of painless and painful intercostobrachial neuropathy. We enrolled 40 women previously undergoing breast cancer surgery. In these patients, we collected, at 3, 6 and 12 months after surgery, clinical and quantitative sensory testing (QST) variables to diagnose intercostobrachial neuropathy, DN4 questionnaire to identify neuropathic pain, Neuropathic Pain Symptom Inventory to assess the different neuropathic pain symptoms, the Beck Depression Inventory to assess depressive symptoms, and SF36 to assess quality of life and Patient Global Impression of Change. Clinical and QST examination showed an intercostobrachial neuropathy in 23 patients (57.5%). Out of the 23 patients, five experienced neuropathic pain, as assessed with clinical examination and DN4. Axillary surgery clearance was associated with an increased risk of intercostobrachial neuropathy. Whereas sensory disturbances improved during the 1-year observation, neuropathic pain did not. Nevertheless, Beck Depression Inventory, SF36, and the Patient Global Impression of Change scores significantly improved over time. Our study shows that although intercostobrachial neuropathy is a common complication of breast cancer surgery, neuropathic pain affects only a minor proportion of patients. After 1 year, sensory disturbances partially improve and have only a mild impact on mood and quality of life.

Pain in chemotherapy-induced neuropathy--more than neuropathic?

PubMed

Geber, Christian; Breimhorst, Markus; Burbach, Berenike; Egenolf, Christina; Baier, Bernhard; Fechir, Marcel; Koerber, Juergen; Treede, Rolf-Detlef; Vogt, Thomas; Birklein, Frank

2013-12-01

Chemotherapy-induced neuropathy (CIN) is an adverse effect of chemotherapy. Pain in CIN might comprise neuropathic and nonneuropathic (ie, musculoskeletal) pain components, which might be characterized by pain patterns, electrophysiology, and somatosensory profiling. Included were 146 patients (100 female, 46 male; aged 56 ± 0.8 years) with CIN arising from different chemotherapy regimens. Patients were characterized clinically through nerve conduction studies (NCS) and quantitative sensory testing (QST). Questionnaires for pain (McGill) and anxiety/depression (Hospital Anxiety and Depression Scale) were supplied. Patients were followed-up after 17 days. Large- (61%) and mixed- (35%) fibre neuropathies were more frequent than small-fibre neuropathy (1.4%). The 5 major chemotherapeutic regimens impacted differently on large- but not on small-fibre function and did not predict painfulness. Chronic pain associated with CIN was reported in 41.7%. Painless and painful CIN did not differ in QST profiles or electrophysiological findings, but different somatosensory patterns were found in CIN subgroups (pain at rest [RestP], n = 25; movement-associated pain [MovP], n = 15; both pain characteristics [MovP+RestP], n = 21; or no pain [NonP], n = 85): small-fibre function (cold-detection threshold, CDT: z score: -1.46 ± 0.21, P < 0.01) was most impaired in RestP; mechanical hyperalgesia was exclusively found in MovP (z score: +0.81 ± 0.30, P < 0.05). "Anxiety" discriminated between painful and painless CIN; "CDT" and "anxiety" discriminated between patients with ongoing (RestP) and movement-associated pain (MovP) or pain components (MovP+RestP). The detrimental effect of chemotherapy on large fibres failed to differentiate painful from painless CIN. Patients stratified for musculoskeletal or neuropathic pain, however, differed in psychological and somatosensory parameters. This stratification might allow for the application of a more specific therapy. Copyright © 2013

Acupuncture for the Treatment of Peripheral Neuropathy: A Systematic Review and Meta-Analysis

PubMed Central

Murchison, Charles; Oken, Barry

2017-01-01

Abstract Objectives: Neuropathy and its associated pain pose great therapeutic challenges. While there has been a recent surge in acupuncture use and research, little remains known about its effects on nerve function. This review aims to assess the efficacy of acupuncture in the treatment of neuropathy of various etiologies. Methods: The Medline, AMED, Cochrane, Scopus, CINAHL, and clintrials.gov databases were systematically searched from inception to July 2015. Randomized controlled trials (RCTs) assessing acupuncture's efficacy for poly- and mononeuropathy were reviewed. Parallel and crossover RCTs focused on acupuncture's efficacy were reviewed and screened for eligibility. The Scale for Assessing Scientific Quality of Investigations in Complementary and Alternative Medicine was used to assess RCT quality. RCTs with score of >9 and active control treatments such as sham acupuncture or medical therapy were included. Results: Fifteen studies were included: 13 original RCTs, a long-term follow-up, and a re-analysis of a prior RCT. The selected RCTs studied acupuncture for neuropathy caused by diabetes, Bell's palsy, carpal tunnel syndrome, human immunodeficiency virus (HIV), and idiopathic conditions. Acupuncture regimens, control conditions, and outcome measures differed among studies, and various methodological issues were identified. Still, the majority of RCTs showed benefit for acupuncture over control in the treatment of diabetic neuropathy, Bell's palsy, and carpal tunnel syndrome. Acupuncture is probably effective in the treatment of HIV-related neuropathy, and there is insufficient evidence for its benefits in idiopathic neuropathy. Acupuncture appears to improve nerve conduction study parameters in both sensory and motor nerves. Meta-analyses were conducted on all diabetic neuropathy and Bell's palsy individual subject data (six RCTs; a total of 680 subjects) using a summary estimate random effects model, which showed combined odds ratio of 4.23 (95

Acupuncture for the Treatment of Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

PubMed

Dimitrova, Alexandra; Murchison, Charles; Oken, Barry

2017-03-01

Neuropathy and its associated pain pose great therapeutic challenges. While there has been a recent surge in acupuncture use and research, little remains known about its effects on nerve function. This review aims to assess the efficacy of acupuncture in the treatment of neuropathy of various etiologies. The Medline, AMED, Cochrane, Scopus, CINAHL, and clintrials.gov databases were systematically searched from inception to July 2015. Randomized controlled trials (RCTs) assessing acupuncture's efficacy for poly- and mononeuropathy were reviewed. Parallel and crossover RCTs focused on acupuncture's efficacy were reviewed and screened for eligibility. The Scale for Assessing Scientific Quality of Investigations in Complementary and Alternative Medicine was used to assess RCT quality. RCTs with score of >9 and active control treatments such as sham acupuncture or medical therapy were included. Fifteen studies were included: 13 original RCTs, a long-term follow-up, and a re-analysis of a prior RCT. The selected RCTs studied acupuncture for neuropathy caused by diabetes, Bell's palsy, carpal tunnel syndrome, human immunodeficiency virus (HIV), and idiopathic conditions. Acupuncture regimens, control conditions, and outcome measures differed among studies, and various methodological issues were identified. Still, the majority of RCTs showed benefit for acupuncture over control in the treatment of diabetic neuropathy, Bell's palsy, and carpal tunnel syndrome. Acupuncture is probably effective in the treatment of HIV-related neuropathy, and there is insufficient evidence for its benefits in idiopathic neuropathy. Acupuncture appears to improve nerve conduction study parameters in both sensory and motor nerves. Meta-analyses were conducted on all diabetic neuropathy and Bell's palsy individual subject data (six RCTs; a total of 680 subjects) using a summary estimate random effects model, which showed combined odds ratio of 4.23 (95% confidence interval 2.3-7.8; p < 0

People with diabetic peripheral neuropathy display a decreased stepping accuracy during walking: potential implications for risk of tripping.

PubMed

Handsaker, J C; Brown, S J; Bowling, F L; Marple-Horvat, D E; Boulton, A J M; Reeves, N D

2016-05-01

To examine the stepping accuracy of people with diabetes and diabetic peripheral neuropathy. Fourteen patients with diabetic peripheral neuropathy (DPN), 12 patients with diabetes but no neuropathy (D) and 10 healthy non-diabetic control participants (C). Accuracy of stepping was measured whilst the participants walked along a walkway consisting of 18 stepping targets. Preliminary data on visual gaze characteristics were also captured in a subset of participants (diabetic peripheral neuropathy group: n = 4; diabetes-alone group: n = 4; and control group: n = 4) during the same task. Patients in the diabetic peripheral neuropathy group, and patients in the diabetes-alone group were significantly less accurate at stepping on targets than were control subjects (P < 0.05). Preliminary visual gaze analysis identified that patients diabetic peripheral neuropathy were slower to look between targets, resulting in less time being spent looking at a target before foot-target contact. Impaired motor control is theorized to be a major factor underlying the changes in stepping accuracy, and potentially altered visual gaze behaviour may also play a role. Reduced stepping accuracy may indicate a decreased ability to control the placement of the lower limbs, leading to patients with neuropathy potentially being less able to avoid observed obstacles during walking. © 2015 Diabetes UK.

Effect of α-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy.

PubMed

Agathos, Evangelos; Tentolouris, Anastasios; Eleftheriadou, Ioanna; Katsaouni, Panagiota; Nemtzas, Ioannis; Petrou, Alexandra; Papanikolaou, Christina; Tentolouris, Nikolaos

2018-05-01

Objective To examine the effect of α-lipoic acid on neuropathic symptoms in patients with diabetic neuropathy (DN). Methods Patients with painful DN were treated with 600 mg/day α-lipoic acid, orally, for 40 days. Neuropathy Symptom Score (NSS), Subjective Peripheral Neuropathy Screen Questionnaire (SPNSQ) and douleur neuropathique (DN)4 questionnaire scores were assessed at baseline and day 40. Quality-of-life treatment effects were assessed by Brief Pain Inventory (BPI), Neuropathic Pain Symptom Inventory (NPSI) and Sheehan Disability Scale (SDS). Changes in body weight, arterial blood pressure, fasting serum glucose and lipids were also assessed. Results Out of 72 patients included, significant reductions in neuropathic symptoms were shown by reduced NSS, SPNSQ and DN4 scores at day 40 versus baseline. BPI, NPSI, and SDS in terms of work disability, social life disability, and family life disability scores were also significantly reduced. Moreover, 50% of patients rated their health condition as 'very much better' or 'much better' following α-lipoic acid administration. Fasting triglyceride levels were reduced, but no difference was found in body weight, blood pressure, fasting glucose, or other lipids at day 40 versus baseline. Conclusions A-lipoic acid administration was associated with reduced neuropathic symptoms and triglycerides, and improved quality of life.

Peripheral neuropathy in complex inherited diseases: an approach to diagnosis.

PubMed

Rossor, Alexander M; Carr, Aisling S; Devine, Helen; Chandrashekar, Hoskote; Pelayo-Negro, Ana Lara; Pareyson, Davide; Shy, Michael E; Scherer, Steven S; Reilly, Mary M

2017-10-01

Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy, for example, spasticity, the type of neuropathy and the other neurological and non-neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy, for example, cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Vitamin D deficiency increases the risk of peripheral neuropathy in Chinese patients with type 2 diabetes.

PubMed

He, Rui; Hu, Yanyun; Zeng, Hui; Zhao, Jun; Zhao, Jungong; Chai, Yimin; Lu, Fengdi; Liu, Fang; Jia, Weiping

2017-02-01

Vitamin D deficiency was reported to be associated with diabetic peripheral neuropathy. But the association in Chinese population and the screening value of vitamin D deficiency for diabetic peripheral neuropathy were unknown. A total of 861 patients with type 2 diabetes were recruited in this cross-sectional study. Vitamin D deficiency was defined as serum circulating 25-hydroxyvitamin D(25(OH)D) level < 20 ng/mL. Peripheral neuropathy was evaluated by neurological symptoms, neurological signs, neurothesiometer and electromyogram. The patients with diabetic peripheral neuropathy had significantly lower serum 25(OH)D concentration (15.59 ± 7.68 ng/mL) and higher prevalence of vitamin D deficiency (80%) than patients with signs of diabetic peripheral neuropathy (17.66 ± 7.50 ng/mL; 64.5%) and non-DPN patients (18.35 ± 6.60; 61.7%) (all p < 0.01). Spearman's correlation analysis showed that serum circulating 25(OH)D level was closely associated with DPN (r = 0.121) and signs of DPN (r = 0.111) (both p < 0.01). After adjusting for all potential confounders, VDD was still linked with increased risk of DPN [odds ratio 2.59 (1.48-4.53)] (p < 0.01). Logistical regression analysis further revealed that VDD was an independent risk factor for DPN (β = 0.88) (p < 0.01). Receiver operating characteristic analysis indicated that serum 25(OH)D < 17.22 ng/mL hinted the signs of DPN and serum 25(OH)D < 16.01 ng/mL predicted the occurrence of DPN (both p < 0.01). Vitamin D deficiency is an independent risk factor for diabetic peripheral neuropathy and may be a potential biomarker for peripheral neuropathy in Chinese patients with type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Selective antagonism of muscarinic receptors is neuroprotective in peripheral neuropathy

PubMed Central

Smith, Darrell R.; Frizzi, Katie; Sabbir, Mohammad Golam; Chowdhury, Subir K. Roy; Mixcoatl-Zecuatl, Teresa; Saleh, Ali; Muttalib, Nabeel; Van der Ploeg, Randy; Ochoa, Joseline; Gopaul, Allison; Tessler, Lori; Wess, Jürgen; Jolivalt, Corinne G.

2017-01-01

Sensory neurons have the capacity to produce, release, and respond to acetylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we have reported that neurite outgrowth from adult sensory neurons that were maintained under subsaturating neurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic receptor–dependent regulation of mitochondrial function via AMPK. Sensory neurons from mice lacking the muscarinic ACh type 1 receptor (M1R) exhibited enhanced neurite outgrowth, confirming the role of M1R in tonic suppression of axonal plasticity. M1R-deficient mice made diabetic with streptozotocin were protected from physiological and structural indices of sensory neuropathy. Pharmacological blockade of M1R using specific or selective antagonists, pirenzepine, VU0255035, or muscarinic toxin 7 (MT7) activated AMPK and overcame diabetes-induced mitochondrial dysfunction in vitro and in vivo. These antimuscarinic drugs prevented or reversed indices of peripheral neuropathy, such as depletion of sensory nerve terminals, thermal hypoalgesia, and nerve conduction slowing in diverse rodent models of diabetes. Pirenzepine and MT7 also prevented peripheral neuropathy induced by the chemotherapeutic agents dichloroacetate and paclitaxel or HIV envelope protein gp120. As a variety of antimuscarinic drugs are approved for clinical use against other conditions, prompt translation of this therapeutic approach to clinical trials is feasible. PMID:28094765

Symptomatic reversal of peripheral neuropathy in patients with diabetes.

PubMed

Kochman, Alan B; Carnegie, Dale H; Burke, Thomas J

2002-03-01

Forty-nine consecutive subjects with established diabetic peripheral neuropathy were treated with monochromatic near-infrared photo energy (MIRE) to determine if there was an improvement of sensation. Loss of protective sensation characterized by Semmes-Weinstein monofilament values of 4.56 and above was present in 100% of subjects (range, 4.56 to 6.45), and 42 subjects (86%) had Semmes-Weinstein values of 5.07 or higher. The ability to discriminate between hot and cold sensation was absent (54%) or impaired (46%) in both groups prior to the initiation of MIRE treatment. On the basis of Semmes-Weinstein monofilament values, 48 subjects (98%) exhibited improved sensation after 6 treatments, and all subjects had improved sensation after 12 treatments. Therefore, MIRE may be a safe, drug-free, noninvasive treatment for the consistent and predictable improvement of sensation in diabetic patients with peripheral neuropathy of the feet.

Generalized peripheral neuropathy in a dental technician exposed to methyl methacrylate monomer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donaghy, M.; Rushworth, G.; Jacobs, J.M.

1991-07-01

A 58-year-old dental prosthetic technician developed generalized sensorimotor peripheral neuropathy. Neurophysiologic studies showed a generalized sensorimotor neuropathy of axonal degeneration type. Examination of a sural nerve biopsy showed a moderately severe axonal neuropathy with loss of large myelinated fibers and unmyelinated axons. There was evidence of slow ongoing degeneration and considerable fiber regeneration. Electron microscopy showed increased numbers of filaments in a few fibers. These findings show resemblances to the nerve changes caused by another acrylic resin, acrylamide. They suggest that the neuropathy may have been caused by 30 years of occupational cutaneous and inhalational exposure to methyl methacrylate monomermore » since they excluded other recognized causes of neuropathy.« less

Living with Fibromyalgia, Drugs Approved to Manage Pain

MedlinePlus

... that can happen in people with diabetes (diabetic peripheral neuropathy) and in those who develop pain following the ... previously approved to treat depression, anxiety, and diabetic peripheral neuropathy. Cymbalta's side effects include nausea, dry mouth, sleepiness, ...

Effect of flavonol and its dimethoxy derivatives on paclitaxel-induced peripheral neuropathy in mice.

PubMed

Sayeli, Vijaykumar; Nadipelly, Jagan; Kadhirvelu, Parimala; Cheriyan, Binoy Varghese; Shanmugasundaram, Jaikumar; Subramanian, Viswanathan

2018-04-13

Peripheral neuropathy is the dose limiting side effect of many anticancer drugs. Flavonoids exhibit good antinociceptive effect in animal models. Their efficacy against different types of nociception has been documented. The present study investigated the effect of flavonol (3-hydroxy flavone), 3',4'-dimethoxy flavonol, 6,3'-dimethoxy flavonol, 7,2'-dimethoxy flavonol and 7,3'-dimethoxy flavonol against paclitaxel-induced peripheral neuropathy in mice. A single dose of paclitaxel (10 mg/kg, i.p.) was administered to induce peripheral neuropathy in mice and the manifestations of peripheral neuropathy such as tactile allodynia, cold allodynia and thermal hyperalgesia were assessed 24 h later by employing Von Frey hair aesthesiometer test, acetone bubble test and hot water tail immersion test, respectively. The test compounds were prepared as a suspension in 0.5% carboxymethyl cellulose and were administered s.c. in various doses (25, 50, 100 and 200 mg/kg). The above behavioral responses were assessed prior to and 30 min after drug treatment. In addition, the effect of test compounds on proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and free radicals was investigated by using suitable in vitro assays. A dose-dependent attenuation of tactile allodynia, cold allodynia and thermal hyperalgesia was evidenced in mice treated with flavonol derivatives. The test compounds inhibited TNF-α, IL-1β and free radicals in a concentration-dependent manner. These results revealed that flavonol and its dimethoxy derivatives ameliorated the manifestations of paclitaxel-induced peripheral neuropathy in mice. The inhibition of proinflammatory cytokines and free radicals could contribute to this beneficial effect.

Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial.

PubMed

de Vos, Cecile C; Meier, Kaare; Zaalberg, Paul Brocades; Nijhuis, Harold J A; Duyvendak, Wim; Vesper, Jan; Enggaard, Thomas P; Lenders, Mathieu W P M

2014-11-01

Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our knowledge, ours is the first multicentre randomized controlled trial investigating the effectiveness of SCS in patients with PDN. Sixty patients with PDN in the lower extremities refractory to conventional medical therapy were enrolled and followed for 6 months. They were randomized 2:1 to best conventional medical practice with (SCS group) or without (control group) additional SCS therapy, and both groups were assessed at regular intervals. At each follow-up visit, the EuroQoL 5D, the short form McGill Pain Questionnaire (SF-MPQ) and a visual analogue scale (VAS, ranging 0-100) to measure pain intensity were recorded. The average VAS score for pain intensity was 73 in the SCS group and 67 in the control group at baseline. After 6 months of treatment, the average VAS score was significantly reduced to 31 in the SCS group (P<.001) and remained 67 (P=.97) in the control group. The SF-MPQ and EuroQoL 5D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced pain and improved quality of life. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Relation of sensory peripheral neuropathy in Sjögren syndrome to anti-Ro/SSA.

PubMed

Scofield, Amanda Kyle; Radfar, Lida; Ice, John A; Vista, Evan; Anaya, Juan-Manuel; Houston, Glen; Lewis, David; Stone, Donald U; Chodosh, James; Hefner, Kimberly; Lessard, Christopher J; Moser, Kathy L; Scofield, Robert Hal

2012-09-01

Sjögren syndrome is a common, chronic autoimmune disease that typically produces inflammation and poor function of the salivary and lacrimal glands. Other organs can be affected, including the nervous system. Sensory peripheral neuropathy is a common manifestation of the disease. Eight-eight patients attending a dry eyes-dry mouth clinic were diagnosed to have primary Sjögren syndrome and underwent a neurological examination. Anti-Ro (or SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno-Lia and BioPlex ANA screen. Serum vitamin B(12) levels were determined using an enzyme-linked microtiter plate assay. Twenty-seven (31%) of the 88 patients had peripheral neuropathy as defined by loss of light touch, proprioception, or vibratory sensation. Anti-Ro and anti-La were found by immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (χ(2) = 8.46, P = 0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) had neuropathy (χ(2) = 5.587, P = 0.018, compared to those without anti-Ro). There was no relationship of the other, more sensitive measures of anti-Ro and anti-La to neuropathy. In addition, we found no association of serum vitamin B(12) levels to neuropathy among these patients with Sjögren syndrome. Sensory peripheral neuropathy is common among patients with Sjögren syndrome and is associated with the presence of anti-Ro and anti-La when determined by immunodiffusion.

The Effect of Exercise on Neuropathic Symptoms, Nerve Function, and Cutaneous Innervation in People with Diabetic Peripheral Neuropathy

PubMed Central

Kluding, Patricia M.; Pasnoor, Mamatha; Singh, Rupali; Jernigan, Stephen; Farmer, Kevin; Rucker, Jason; Sharma, Neena; Wright, Douglas E.

2012-01-01

Although exercise can significantly reduce the prevalence and severity of diabetic complications, no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy (DPN). The purpose of this pilot study was to examine feasibility and effectiveness of a supervised, moderately intense aerobic and resistance exercise program in people with DPN. We hypothesize that the exercise intervention can improve neuropathic symptoms, nerve function, and cutaneous innervation. Methods A pre-test post-test design was to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program. Seventeen subjects with diagnosed DPN (8 males/9 females; age 58.4±5.98; duration of diabetes 12.4±12.2 years) completed the study. Outcome measures included pain measures (visual analog scale), Michigan Neuropathy Screening Instrument (MNSI) questionnaire of neuropathic symptoms, nerve function measures, and intraepidermal nerve fiber (IENF) density and branching in distal and proximal lower extremity skin biopsies. Results Significant reductions in pain (−18.1±35.5 mm on a 100 mm scale, p=0.05), neuropathic symptoms (−1.24±1.8 on MNSI, p=0.01), and increased intraepidermal nerve fiber branching (+0.11±0.15 branch nodes/fiber, p=−.008) from a proximal skin biopsy were noted following the intervention. Conclusions This is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy. These findings are particularly promising given the short duration of the intervention, but need to be validated by comparison with a control group in future studies. PMID:22717465

The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy.

PubMed

Kluding, Patricia M; Pasnoor, Mamatha; Singh, Rupali; Jernigan, Stephen; Farmer, Kevin; Rucker, Jason; Sharma, Neena K; Wright, Douglas E

2012-01-01

Although exercise can significantly reduce the prevalence and severity of diabetic complications, no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy (DPN). The purpose of this pilot study was to examine feasibility and effectiveness of a supervised, moderately intense aerobic and resistance exercise program in people with DPN. We hypothesized that the exercise intervention can improve neuropathic symptoms, nerve function, and cutaneous innervation. A pre-test post-test design was used to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program. Seventeen subjects with diagnosed DPN (8 males/9 females; age 58.4±5.98; duration of diabetes 12.4±12.2 years) completed the study. Outcome measures included pain measures (visual analog scale), Michigan Neuropathy Screening Instrument (MNSI) questionnaire of neuropathic symptoms, nerve function measures, and intraepidermal nerve fiber (IENF) density and branching in distal and proximal lower extremity skin biopsies. Significant reductions in pain (-18.1±35.5 mm on a 100 mm scale, P=.05), neuropathic symptoms (-1.24±1.8 on MNSI, P=.01), and increased intraepidermal nerve fiber branching (+0.11±0.15 branch nodes/fiber, P=.008) from a proximal skin biopsy were noted following the intervention. This is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy. These findings are particularly promising given the short duration of the intervention, but need to be validated by comparison with a control group in future studies. Copyright © 2012 Elsevier Inc. All rights reserved.

Evidence from Human and Animal Studies: Pathological Roles of CD8+ T Cells in Autoimmune Peripheral Neuropathies

PubMed Central

Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

2015-01-01

Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies. PMID:26528293

Evidence from Human and Animal Studies: Pathological Roles of CD8(+) T Cells in Autoimmune Peripheral Neuropathies.

PubMed

Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

2015-01-01

Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4(+) T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4(+) T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8(+) T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8(+) T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8(+) T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4(+) T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8(+) T cells in autoimmune peripheral neuropathies.

Hereditary sensory and autosomal peripheral neuropathy-type IV: case series and review of literature.

PubMed

Ashwin, D P; Chandan, G D; Jasleen, Handa Kaur; Rajkumar, G C; Rudresh, K B; Prashanth, R

2015-06-01

Hereditary sensory and autonomic neuropathy (HSAN) IV is a rare autosomal recessive disorder which is characterized by a decrease in the number of myelinated and non-myelinated nerve fibers of peripheral nerves which causes diminished or absent pain sensation leading to increase in self-mutilative habits. A retrospective study of eight cases ranging from age group of 4 to 17 years for oral and digital signs and symptoms is presented. All the patients showed congenital insensitivity to pain and anhidrosis. Oral self-mutilations, such as autoextraction of teeth and severe bite injuries (with resultant scarring) of the finger tips and oral soft tissues (tongue, lip, and buccal mucosa) were found in most patients. Our study suggests that early diagnosis and specific treatment plan are important for prevention of characteristic of the oral as well as digital trauma associated with this disorder.

Role of insulin signaling impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice.

PubMed

Anderson, Nicholas J; King, Matthew R; Delbruck, Lina; Jolivalt, Corinne G

2014-06-01

One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype. © 2014. Published by The Company of Biologists Ltd.

Acupuncture in Reducing Chemotherapy-Induced Peripheral Neuropathy in Participants With Stage I-III Breast Cancer

ClinicalTrials.gov

2018-06-27

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Grade 1 Peripheral Motor Neuropathy, CTCAE; Grade 1 Peripheral Sensory Neuropathy, CTCAE; Grade 2 Peripheral Motor Neuropathy, CTCAE; Grade 2 Peripheral Sensory Neuropathy, CTCAE; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8

Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy.

PubMed

Brazill, Jennifer M; Cruz, Beverley; Zhu, Yi; Zhai, R Grace

2018-06-12

Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side effect of many commonly used chemotherapeutic agents, including paclitaxel. Currently, there are no neuroprotective or effective symptomatic treatments for CIPN. Lack of understanding of the in vivo mechanisms of CIPN has greatly impeded the identification of therapeutic targets. Here, we optimized a model of paclitaxel-induced peripheral neuropathy using Drosophila larvae that recapitulates aspects of chemotherapy-induced sensory dysfunction . We showed that nociceptive sensitivity is associated with disrupted organization of microtubule-associated MAP1B/Futsch and aberrant stabilization of peripheral sensory dendrites. These findings establish a robust and amenable model for studying peripheral mechanisms of CIPN. Using this model, we uncovered a critical role for nicotinamide mononucleotide adenylyltransferase (Nmnat) in maintaining the integrity and function of peripheral sensory neurons and uncovered Nmnat's therapeutic potential against diverse sensory symptoms of CIPN. © 2018. Published by The Company of Biologists Ltd.

Computer aided diagnosis of diabetic peripheral neuropathy

NASA Astrophysics Data System (ADS)

Chekh, Viktor; Soliz, Peter; McGrew, Elizabeth; Barriga, Simon; Burge, Mark; Luan, Shuang

2014-03-01

Diabetic peripheral neuropathy (DPN) refers to the nerve damage that can occur in diabetes patients. It most often affects the extremities, such as the feet, and can lead to peripheral vascular disease, deformity, infection, ulceration, and even amputation. The key to managing diabetic foot is prevention and early detection. Unfortunately, current existing diagnostic techniques are mostly based on patient sensations and exhibit significant inter- and intra-observer differences. We have developed a computer aided diagnostic (CAD) system for diabetic peripheral neuropathy. The thermal response of the feet of diabetic patients following cold stimulus is captured using an infrared camera. The plantar foot in the images from a thermal video are segmented and registered for tracking points or specific regions. The temperature recovery of each point on the plantar foot is extracted using our bio-thermal model and analyzed. The regions that exhibit abnormal ability to recover are automatically identified to aid the physicians to recognize problematic areas. The key to our CAD system is the segmentation of infrared video. The main challenges for segmenting infrared video compared to normal digital video are (1) as the foot warms up, it also warms up the surrounding, creating an ever changing contrast; and (2) there may be significant motion during imaging. To overcome this, a hybrid segmentation algorithm was developed based on a number of techniques such as continuous max-flow, model based segmentation, shape preservation, convex hull, and temperature normalization. Verifications of the automatic segmentation and registration using manual segmentation and markers show good agreement.

[Treatment Results of Low Back and Leg Pain Considering Para-Lumbar Spine Disease and Peripheral Nerve Neuropathy].

PubMed

Iwamoto, Naotaka; Isu, Toyohiko; Kim, Kyongsong; Morimoto, Daijiro; Matsumoto, Juntaro; Yamazaki, Kazuyoshi; Chiba, Yasuhiro; Isobe, Masanori

2018-06-01

Here we report our treatment results of low back and leg pain(LBLP)considering para-lumbar spine disease(PLSD)and peripheral nerve neuropathy(PNN). We enrolled 103 patients who were admitted to our institute for LBLP treatment between January and December in 2014. For the treatment, we preferentially performed intensive block therapy for PLSD. Among 103 patients, 89 patients had PLSD. In 85 patients, we performed intensive block therapy and 82 patients experienced short-term improvement of symptoms. In 35 of these 82 patients, lumbar spine and/or PNN surgical treatment was required as the effect of block therapy was transient. Intensive block therapy was effective in 47 of 103 patients(45.6%), and the remaining patients required surgical treatment(PLSD and/or PNN:31 cases, lumbar spine:13 cases, both:8 cases). Among 103 patients with LBLP, intensive block therapy for PLSD and PNN was useful for short-term symptom improvement in 82 patients(79.6%), and for long-term symptom improvement in 47 patients(45.6%)as evaluated at the final follow-up. Surgical treatment of PLSD and/or PNN was required in 39 patients(37.9%). These results suggested that treatment of PLSD and PNN might yield good results for patients with LBLP.

Randomized Placebo-Controlled Double-Blind Clinical Trial of Cannabis-Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy

PubMed Central

Selvarajah, Dinesh; Gandhi, Rajiv; Emery, Celia J.; Tesfaye, Solomon

2010-01-01

OBJECTIVE To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments. RESULTS There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention. CONCLUSIONS This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN. PMID:19808912

Effects of diabetic peripheral neuropathy on gait in vascular trans-tibial amputees.

PubMed

Nakajima, Hiroshi; Yamamoto, Sumiko; Katsuhira, Junji

2018-07-01

Patients with diabetes often develop diabetic peripheral neuropathy, which is a distal symmetric polyneuropathy, so foot function on the non-amputated side is expected to affect gait in vascular trans-tibial amputees. However, there is little information on the kinematics and kinetics of gait or the effects of diabetic peripheral neuropathy in vascular trans-tibial amputees. This study aimed to clarify these effects, including the biomechanics of the ankle on the non-amputated side. Participants were 10 vascular trans-tibial amputees with diabetic peripheral neuropathy (group V) and 8 traumatic trans-tibial amputees (group T). Each subject's gait was analyzed at a self-selected speed using a three-dimensional motion analyzer and force plates. Ankle plantarflexion angle, heel elevation angle, and peak and impulse of anterior ground reaction force were smaller on the non-amputated side during pre-swing in group V than in group T. Center of gravity during pre-swing on the non-amputated side was lower in group V than in group T. Hip extension torque during loading response on the prosthetic side was greater in group V than in group T. These findings suggest that the biomechanical function of the ankle on the non-amputated side during pre-swing is poorer in vascular trans-tibial amputees with DPN than in traumatic trans-tibial amputees; the height of the center of gravity could not be maintained during this phase in vascular trans-tibial amputees with diabetic peripheral neuropathy. The hip joint on the prosthetic side compensated for this diminished function at the ankle during loading response. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K.

PubMed

Abbott, Caroline A; Malik, Rayaz A; van Ross, Ernest R E; Kulkarni, Jai; Boulton, Andrew J M

2011-10-01

To assess, in the general diabetic population, 1) the prevalence of painful neuropathic symptoms; 2) the relationship between symptoms and clinical severity of neuropathy; and 3) the role of diabetes type, sex, and ethnicity in painful neuropathy. Observational study of a large cohort of diabetic patients receiving community-based health care in northwest England (n = 15,692). Painful diabetic neuropathy (PDN) was assessed using neuropathy symptom score (NSS) and neuropathy disability score (NDS). Prevalence of painful symptoms (NSS ≥5) and PDN (NSS ≥5 and NDS ≥3) was 34 and 21%, respectively. Painful symptoms occurred in 26% of patients without neuropathy (NDS ≤2) and 60% of patients with severe neuropathy (NDS >8). Adjusted risk of painful neuropathic symptoms in type 2 diabetes was double that of type 1 diabetes (odds ratio [OR] = 2.1 [95% CI 1.7-2.4], P < 0.001) and not affected by severity of neuropathy, insulin use, foot deformities, smoking, or alcohol. Women had 50% increased adjusted risk of painful symptoms compared with men (OR = 1.5 [1.4-1.6], P < 0.0001). Despite less neuropathy in South Asians (14%) than Europeans (22%) and African Caribbeans (21%) (P < 0.0001), painful symptoms were greater in South Asians (38 vs. 34 vs. 32%, P < 0.0001). South Asians without neuropathy maintained a 50% increased risk of painful neuropathy symptoms compared with other ethnic groups (P < 0.0001). One-third of all community-based diabetic patients have painful neuropathy symptoms, regardless of their neuropathic deficit. PDN was more prevalent in patients with type 2 diabetes, women, and people of South Asian origin. This highlights a significant morbidity due to painful neuropathy and identifies key groups who warrant screening for PDN.

Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy.

PubMed

Yarnitsky, David; Granot, Michal; Nahman-Averbuch, Hadas; Khamaisi, Mogher; Granovsky, Yelena

2012-06-01

This study aims to individualize the selection of drugs for neuropathic pain by examining the potential coupling of a given drug's mechanism of action with the patient's pain modulation pattern. The latter is assessed by the conditioned pain modulation (CPM) and temporal summation (TS) protocols. We hypothesized that patients with a malfunctioning pain modulation pattern, such as less efficient CPM, would benefit more from drugs augmenting descending inhibitory pain control than would patients with a normal modulation pattern of efficient CPM. Thirty patients with painful diabetic neuropathy received 1 week of placebo, 1 week of 30 mg/d duloxetine, and 4 weeks of 60 mg/d duloxetine. Pain modulation was assessed psychophysically, both before and at the end of treatment. Patient assessment of drug efficacy, assessed weekly, was the study's primary outcome. Baseline CPM was found to be correlated with duloxetine efficacy (r=0.628, P<.001, efficient CPM is marked negative), such that less efficient CPM predicted efficacious use of duloxetine. Regression analysis (R(2)=0.673; P=.012) showed that drug efficacy was predicted only by CPM (P=.001) and not by pretreatment pain levels, neuropathy severity, depression level, or patient assessment of improvement by placebo. Furthermore, beyond its predictive value, the treatment-induced improvement in CPM was correlated with drug efficacy (r=-0.411, P=.033). However, this improvement occurred only in patients with less efficient CPM (16.8±16.0 to -1.1±15.5, P<.050). No predictive role was found for TS. In conclusion, the coupling of CPM and duloxetine efficacy highlights the importance of pain pathophysiology in the clinical decision-making process. This evaluative approach promotes personalized pain therapy. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Extremely Painful Multifocal Acquired Predominant Axonal Sensorimotor Neuropathy of the Upper Limb.

PubMed

Lieba-Samal, Doris; van Eijk, Jeroen J J; van Rosmalen, Marieke H J; van Balken, Irene M F; Verrips, Aad; Mostert, Jop; Pillen, Sigrid; van Alfen, Nens

2018-06-01

The differential diagnosis of upper extremity mononeuritis multiplex includes neuralgic amyotrophy, vasculitic neuropathy, and Lewis-Sumner syndrome. We describe 3 patients initially suspected of neuralgic amyotrophy, who had an extremely painful, protracted, progressive disease course, not fitting one of these established diagnoses. Nerve ultrasonography showed focal caliber changes of the roots, plexus, and limb nerves. Electromyography showed predominant multifocal axonopathy. Ongoing autoimmune neuropathy was suspected. Steroid treatment provided temporary relief, and intravenous immunoglobulin A sustained pain decrease and functional improvement. These patients appear to have extremely painful axonal inflammatory neuropathy, with a good response to immune-modulating treatment. © 2017 by the American Institute of Ultrasound in Medicine.

Relation of Sensory Peripheral Neuropathy in Sjögren Syndrome to anti-Ro/SSA

PubMed Central

Scofield, Amanda K.; Radfar, Lida; Ice, John; Vista, Evan; Anaya, Juan-Manuel; Houston, Glen; Lewis, David; Stone, Donald U.; Chodosh, James; Hefner, Kimberly; Lessard, Christopher J.; Moser, Kathy L.; Scofield, R. Hal

2013-01-01

Background Sjögren syndrome is a common, chronic autoimmune disease that typically produces inflammation and poor function of the salivary and lacrimal glands. Other organs can be affected, including the nervous system. Sensory peripheral neuropathy is a common manifestation of the disease. Methods Eight-eight patients attending a dry eyes-dry mouth clinic were classified as primary Sjögren syndrome and underwent a neurological examination. Anti-Ro (or SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno-Lia and BioPlex ANA screen. Serum vitamin B12 levels were determined using an enzyme-linked microtiter plate assay. Results Twenty-seven (31%) of the 88 patients had peripheral neuropathy as defined by loss of light touch, proprioception or vibratory sensation. Anti-Ro and anti-La were found by immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (χ2=8.46, p=0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) of these had neuropathy (χ2 =5.587, p=0.018 compared to those without anti-Ro). There was no relationship of the other, more sensitive measures of anti-Ro and anti-La to neuropathy. In addition, we found no association of serum vitamin B12 levels to neuropathy among these patients with Sjögren syndrome. Conclusion Sensory peripheral neuropathy is common among patients with Sjögren syndrome, and is associated with the presence of anti-Ro and anti-La when determined by immunodiffusion. PMID:22955477

Clinical spectrum of Castleman disease–associated neuropathy

PubMed Central

Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay

2016-01-01

Objective: To define the peripheral neuropathy phenotypes associated with Castleman disease. Methods: We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. Results: There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. Conclusion: There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. PMID:27807187

Clinical spectrum of Castleman disease-associated neuropathy.

PubMed

Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay; Mauermann, Michelle L

2016-12-06

To define the peripheral neuropathy phenotypes associated with Castleman disease. We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. © 2016 American Academy of Neurology.

Concurrent outbreaks of cholera and peripheral neuropathy associated with high mortality among persons internally displaced by a volcanic eruption.

PubMed

Rosewell, Alexander; Clark, Geoff; Mabong, Paul; Ropa, Berry; Posanai, Enoch; Man, Nicola W Y; Dutta, Samir R; Wickramasinghe, Wasa; Qi, Lixia; Ng, Jack C; Mola, Glen; Zwi, Anthony B; MacIntyre, C Raina

2013-01-01

In October 2004, Manam Island volcano in Papua New Guinea erupted, causing over 10 000 villagers to flee to internally displaced person (IDP) camps, including 550 from Dugulaba village. Following violence over land access in March 2010, the IDPs fled the camps, and four months later concurrent outbreaks of acute watery diarrhea and unusual neurological complaints were reported in this population. A retrospective case-control study was conducted to identify the risk factors for peripheral neuropathy. Rectal swabs were collected from cases of acute watery diarrhea. Hair and serum metals and metalloids were analyzed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). There were 17 deaths among the 550 village inhabitants during the outbreak period at a crude mortality rate 21-fold that of a humanitarian crisis. Vibrio cholerae O1 El Tor Ogawa was confirmed among the population. Access to community-level rehydration was crucial to mortality. Peripheral neuropathy was diagnosed among cases with neurological symptoms. A balanced diet was significantly protective against neuropathy. A dose-response relationship was seen between peripheral neuropathy and a decreasing number of micronutrient- rich foods in the diet. Deficiencies in copper, iron, selenium and zinc were identified among the cases of peripheral neuropathy. Cholera likely caused the mostly preventable excess mortality. Peripheral neuropathy was not caused by cholera, but cholera may worsen existing nutritional deficiencies. The peripheral neuropathy was likely caused by complex micronutrient deficiencies linked to non-diversified diets that potentially increased the vulnerability of this population, however a new zinc-associated neuropathy could not be ruled out. Reoccurrence can be prevented by addressing the root cause of displacement and ensuring access to arable land and timely resettlement.

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy.

PubMed

Tang, Wei; Chen, Xiangfang; Liu, Haoqi; Lv, Qian; Zou, Junjie; Shi, Yongquan; Liu, Zhimin

2018-04-26

High glucose-induced oxidative stress and inflammatory responses play an important role in painful diabetic neuropathy by activating the TLR4/NFκB signal pathway. Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs provide a microenvironment favoring vascular regeneration but their low survival ratio in hyperglycemic conditions suppress the function to promote nerve growth. Nuclear factor erythroid 2-related factor 2 (Nrf2) promotes remyelination after peripheral nerve injury. The aim of this study was to identify the role of Nrf2 in SC-mediated functional recovery after sciatic nerve injury. We compared plasma inflammatory factors in diabetic patients (DN) with/without diabetic peripheral neuropathy (DPN) and assessed whether Nrf2 expression in SCs could repair peripheral nerve injury in a rat model. Nrf2, TLR4/NFκB signal pathway and apoptosis relative protein expression were detected by western blot. Apoptosis and angiogenesis were determined by immunofluorescence and tubule formation assay, respectively. Regenerated nerves were determined by transmission electron microscope. Higher levels of inflammatory factors and VEGF expression were found in DPN patients. Cellular experiments indicate that Nrf2 expression inhibits hyperglycemia-induced apoptosis and promotes angiogenesis by regulating the TLR4/NFκB signal pathway. Animal experiments show that nerve conduction velocity, myelin sheath thickness, and sciatic vasa nervorum are restored with transplantation of SCs overexpressing Nrf2. Taken together, the high survival ratio of SCs in a DPN rat model indicates that overexpression of Nrf2 restores nerve injury. © 2018 The Author(s). Published by S. Karger AG, Basel.

Characteristics, treatment, and health care expenditures of Medicare supplemental-insured patients with painful diabetic peripheral neuropathy, post-herpetic neuralgia, or fibromyalgia.

PubMed

Johnston, Stephen S; Udall, Margarita; Alvir, Jose; McMorrow, Donna; Fowler, Robert; Mullins, Daniel

2014-04-01

To describe the characteristics, treatment, and health care expenditures of Medicare Supplemental-insured patients with painful diabetic peripheral neuropathy (pDPN), post-herpetic neuralgia (PHN), or fibromyalgia. Retrospective cohort study. United States clinical practice, as reflected within a database comprising administrative claims from 2.3 million older adults participating in Medicare supplemental insurance programs. Selected patients were aged ≥65 years, continuously enrolled in medical and prescription benefits throughout years 2008 and 2009, and had ≥1 medical claim with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for DPN, PHN, or fibromyalgia, followed within 60 days by a medication or pain intervention procedure used in treating pDPN, PHN, or fibromyalgia during 2008-2009. Utilization of, and expenditures on, pain-related and all-cause pharmacotherapy and medical interventions in 2009. The study included 25,716 patients with pDPN (mean age 75.2 years, 51.2% female), 4,712 patients with PHN (mean age 77.7 years, 63.9% female), and 25,246 patients with fibromyalgia (mean age 74.4 years, 73.0% female). Patients typically had numerous comorbidities, and many were treated with polypharmacy. Mean annual expenditures on total pain-related health care and total all-cause health care, respectively, (in 2010 USD) were: $1,632, $24,740 for pDPN; $1,403, $16,579 for PHN; and $1,635, $18,320 for fibromyalgia. In age-stratified analyses, pain-related health care expenditures decreased as age increased. The numerous comorbidities, polypharmacy, and magnitude of expenditures in this sample of Medicare supplemental-insured patients with pDPN, PHN, or fibromyalgia underscore the complexity and importance of appropriate management of these chronic pain patients. Wiley Periodicals, Inc.

An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy.

PubMed

Gupta, Kamesh; Jain, Anand; Rohatgi, Anurag

A descriptive, observational study was completed in a tertiary care hospital between November 2014 and March 2016. Fifty consecutive patients of Type 2-Diabetes Mellitus who had been on metformin therapy for at least three months were included in our study. Several Parameters were compared with vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS) and Nerve Conduction Velocity). These included the duration of diabetes, duration of metformin usage, dietary history, and HbA1c levels. Definite B12 deficiency was defined as B12<150pg/ml and possible B12 deficiency as <220pg/ml. In our study, we found a negative correlation between duration of metformin use and Vitamin B12 levels(r=-0.40). The mean Vitamin B12 levels seen in our study was 212.3pg/mL. There is a positive correlation between the duration of metformin therapy and peripheral neuropathy (r=0.40). The mean TCSS score was 6.8. The percentage of patients with mild neuropathy was 28%, with moderate neuropathy was 20% and severe neuropathy in 12% of the patients. The average duration of metformin use in patients without peripheral neuropathy was 5.5yrs whereas the average length of metformin use in patients with peripheral neuropathy was 10.4 yrs. Patients on long-term metformin therapy are at a high risk for Vitamin B12 deficiency and peripheral neuropathy. Interval Screening for peripheral neuropathy is recommended for patients on metformin even if Vitamin B12 levels appear to be normal. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Oleo gum resin of Ferula assa-foetida L. ameliorates peripheral neuropathy in mice.

PubMed

Homayouni Moghadam, Farshad; Dehghan, Maryam; Zarepur, Ehsan; Dehlavi, Reyhaneh; Ghaseminia, Fatemeh; Ehsani, Shima; Mohammadzadeh, Golnaz; Barzegar, Kazem

2014-05-28

According to the Chinese, European, Iranian and Indian traditional medicines, oleo gum resin of Ferula assa-foetida (asafoetida) has therapeutic effects on different kinds of diseases. Some of these effects are related to the diseases of nervous system such as hysteresis and convulsion. In recent studies, some anti-epileptic and neuroprotective roles were also considered for it and we examined its possible role on treatment of peripheral neuropathy. in vitro studies were carried out to identify the response of isolated sciatic nerves to different concentrations of oleo gum resin of asafoetida solved in Lock׳s solution. Then, in vivo studies were conducted to evaluate its effect on amelioration of peripheral neuropathy in mice. Peripheral neuropathy was induced by intraperiotoneal injection of high doses of pyridoxine in adult Balb/c male mice. Tail flick tests were performed to identify the incidence of neuropathy in animals. After 10 days treatment with asafoetida, the efficiency of treatment was assessed by behavioral, electrophysiological and histological studies. in vitro experiments confirmed that incubating the nerves in aqueous extract of oleo gum rein of asafoetida increased the amplitude and decreased the latent period of nerve compound action potential (CAP). Nerve conduction velocity (NCV) and amplitude of CAP also improved in asafoetida treated animals. Histological and behavioral studies showed that asafoetida was able to facilitate the healing process in peripheral nerves. in vitro experiments showed that asafoetida is a nerve stimulant and its administration in neuropathic mice exerted neuroprotecting effects through stimulating axonal regeneration and remyelination and decrement of lymphocyte infiltration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Measuring Vincristine-Induced Peripheral Neuropathy in Children with Acute Lymphoblastic Leukemia

PubMed Central

Lavoie Smith, Ellen M.; Li, Lang; Hutchinson, Raymond J.; Ho, Richard; Burnette, W. Bryan; Wells, Elizabeth; Bridges, Celia; Renbarger, Jamie

2014-01-01

Background Vincristine-induced peripheral neuropathy (VIPN) is difficult to quantify in children. Objective The study objective was to examine the reliability, validity, and clinical feasibility of several VIPN measures for use in children with acute lymphoblastic leukemia. Interventions/Methods Children (N = 65) aged 1–18 years receiving vincristine at four academic centers participated in the study. Baseline and pre-vincristine VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS-PV), the National Cancer Institute Common Terminology Criteria for Adverse Events, the Balis grading scale, and the FACES pain scale. TNS-PV scores (n = 806) were obtained over 15 weeks. Blood was obtained at several time-points to quantify pharmacokinetic parameters. Results Cronbach’s alpha for a reduced TNS-PV scale was 0.84. TNS-PV scores correlated with cumulative vincristine dosage (r = 0.53, p = 0.01), pharmacokinetic parameters (r = 0.41, p = 0.05), and grading scale scores (r = 0.46 – 0.52; p = 0.01). FACES scores correlated with the TNS-PV neuropathic pain item (r = 0.48; p = 0.01), and were attainable in all ages. A 2-item V-Rex score (vibration and reflex items) was the most responsive to change (es 0.65, p < 0.001). TNS-PV scores were attainable in 95% of children ≥ 6 years. Conclusions The TNS-PV is reliable and valid for measuring VIPN. It is sensitive to change over time (15 weeks) and feasible for use in children ≥ 6 years of age. Implications for Practice The TNS-PV may be a useful tool for assessing vincristine toxicity in children with acute lymphoblastic leukemia. PMID:23842524

Peripheral neuropathy in children with type 1 diabetes.

PubMed

Louraki, M; Karayianni, C; Kanaka-Gantenbein, C; Katsalouli, M; Karavanaki, K

2012-10-01

Diabetic neuropathy (DN) is a major complication of type 1 diabetes mellitus (T1DM) with significant morbidity and mortality in adulthood. Clinical neuropathy is rarely seen in paediatric populations, whereas subclinical neuropathy is commonly seen, especially in adolescents. Peripheral DN involves impairment of the large and/or small nerve fibres, and can be diagnosed by various methods. Nerve conduction studies (NCS) are the gold-standard method for the detection of subclinical DN; however, it is invasive, difficult to perform and selectively detects large-fibre abnormalities. Vibration sensation thresholds (VSTs) and thermal discrimination thresholds (TDTs) are quicker and easier and, therefore, more suitable as screening tools. Poor glycaemic control is the most important risk factor for the development of DN. Maintaining near-normoglycaemia is the only way to prevent or reverse neural impairment, as the currently available treatments can only relieve the symptoms of DN. Early detection of children and adolescents with nervous system abnormalities is crucial to allow all appropriate measures to be taken to prevent the development of DN. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC).

PubMed

Dalakas, M C; Semino-Mora, C; Leon-Monzon, M

2001-11-01

The 2'3'-dideoxycytidine (ddC), a nonazylated dideoxynucleoside analog used for the treatment of AIDS, causes a dose-dependent, painful, sensorimotor axonal peripheral neuropathy in up to 30% of the patients. To investigate the cause of the neuropathy, we performed morphological and molecular studies on nerve biopsy specimens from well-selected patients with ddC-neuropathy and from control subjects with disease, including patients with AIDS-related neuropathy never treated with ddC. Because ddC, in vitro, inhibits the replication of mitochondrial DNA (mtDNA), we counted the number of normal and abnormal mitochondria in a 0.04 mm(2) cross-sectional area of the nerves and quantified the copy numbers of mtDNA by competitive PCR in all specimens. A varying degree of axonal degeneration was present in all nerves. Abnormal mitochondria with enlarged size, excessive vacuolization, electron-dense concentric inclusions and degenerative myelin structures were prominent in the ddC-neuropathy and accounted for 55% +/- 2.5% of all counted mitochondria in the axon and Schwann cells, compared with 9% +/- 0.7% of the controls (p < 0.001). Significantly (p < 0.005) reduced copy numbers, with as high as 80% depletion, of the mtDNA was demonstrated in the nerves of the ddC-treated patients compared with the controls. We conclude that ddC induces a mitochondrial neuropathy with depletion of the nerve's mtDNA. The findings are consistent with the ability of ddC to selectively inhibit the gamma-DNA polymerase in neuronal cell lines. Toxicity to mitochondria of the peripheral nerve is a new cause of acquired neuropathy induced by exogenous toxins and may be the cause of neuropathy associated with the other neurotoxic antiretroviral drugs or toxic-metabolic conditions.

Concurrent Outbreaks of Cholera and Peripheral Neuropathy Associated with High Mortality among Persons Internally Displaced by a Volcanic Eruption

PubMed Central

Rosewell, Alexander; Clark, Geoff; Mabong, Paul; Ropa, Berry; Posanai, Enoch; Man, Nicola W. Y.; Dutta, Samir R.; Wickramasinghe, Wasa; Qi, Lixia; Ng, Jack C.; Mola, Glen; Zwi, Anthony B.; MacIntyre, C. Raina

2013-01-01

Background In October 2004, Manam Island volcano in Papua New Guinea erupted, causing over 10 000 villagers to flee to internally displaced person (IDP) camps, including 550 from Dugulaba village. Following violence over land access in March 2010, the IDPs fled the camps, and four months later concurrent outbreaks of acute watery diarrhea and unusual neurological complaints were reported in this population. Materials and Methods A retrospective case-control study was conducted to identify the risk factors for peripheral neuropathy. Rectal swabs were collected from cases of acute watery diarrhea. Hair and serum metals and metalloids were analyzed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Results There were 17 deaths among the 550 village inhabitants during the outbreak period at a crude mortality rate 21-fold that of a humanitarian crisis. Vibrio cholerae O1 El Tor Ogawa was confirmed among the population. Access to community-level rehydration was crucial to mortality. Peripheral neuropathy was diagnosed among cases with neurological symptoms. A balanced diet was significantly protective against neuropathy. A dose-response relationship was seen between peripheral neuropathy and a decreasing number of micronutrient- rich foods in the diet. Deficiencies in copper, iron, selenium and zinc were identified among the cases of peripheral neuropathy. Conclusions Cholera likely caused the mostly preventable excess mortality. Peripheral neuropathy was not caused by cholera, but cholera may worsen existing nutritional deficiencies. The peripheral neuropathy was likely caused by complex micronutrient deficiencies linked to non-diversified diets that potentially increased the vulnerability of this population, however a new zinc-associated neuropathy could not be ruled out. Reoccurrence can be prevented by addressing the root cause of displacement and ensuring access to arable land and timely resettlement. PMID:24023752

Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions

PubMed Central

Javed, Saad; Alam, Uazman; Malik, Rayaz A.

2015-01-01

Diabetic peripheral neuropathies (DPN) are a heterogeneous group of disorders caused by neuronal dysfunction in patients with diabetes. They have differing clinical courses, distributions, fiber involvement (large or small), and pathophysiology. These complications are associated with increased morbidity, distress, and healthcare costs. Approximately 50% of patients with diabetes develop peripheral neuropathy, and the projected rise in the global burden of diabetes is spurring an increase in neuropathy. Distal symmetrical polyneuropathy (DSPN) with painful diabetic neuropathy, occurring in around 20% of diabetes patients, and diabetic autonomic neuropathy (DAN) are the most common manifestations of DPN. Optimal glucose control represents the only broadly accepted therapeutic option though evidence of its benefit in type 2 diabetes is unclear. A number of symptomatic treatments are recommended in clinical guidelines for the management of painful DPN, including antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids, and topical agents such as capsaicin. However, monotherapy is frequently not effective in achieving complete resolution of pain in DPN. There is a growing need for head-to-head studies of different single-drug and combination pharmacotherapies. Due to the ubiquity of autonomic innervation in the body, DAN causes a plethora of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. The current treatment of DAN is largely symptomatic, and does not correct the underlying autonomic nerve deficit. A number of novel potential candidates, including erythropoietin analogues, angiotensin II receptor type 2 antagonists, and sodium channel blockers are currently being evaluated in phase II clinical trials. PMID:26676662

Effectiveness of aquatic versus land physiotherapy in the treatment of peripheral neuropathies: a randomized controlled trial.

PubMed

Zivi, Ilaria; Maffia, Sara; Ferrari, Vanessa; Zarucchi, Alessio; Molatore, Katia; Maestri, Roberto; Frazzitta, Giuseppe

2018-05-01

To compare the effects on gait and balance of aquatic physiotherapy versus on-land training, in the context of an inpatient rehabilitation treatment tailored for peripheral neuropathies. Parallel-group, single-center, single-blind randomized controlled trial. Consecutive patients affected by peripheral neuropathy admitted in our Neuro-Rehabilitation Unit. Patients received a four-week rehabilitation program composed by daily sessions of conventional physiotherapy and three sessions/week of specific treatment (aquatic vs. on-land). Primary outcome measures were Berg Balance Scale and Dynamic Gait Index. Secondary outcome measures were Neuropathic Pain Scale, Overall Neuropathy Limitations Scale, Functional Independence Measure, Functional Ambulation Classification, Conley Scale and Medical Research Council Scale score for the strength of hip and ankle flexor and extensor muscles. For each scale, we calculated the difference between the scores at discharge and admission and compared it between the two groups. Forty patients were enrolled: 21 in the water-based rehabilitation group and 19 in the land-based one. Patients were similar between groups. When comparing the groups, we found that "in-water" patients had a significant better improvement in the Dynamic Gait Index score (6.00 (4.00, 7.25) vs. 4.00 (1.25, 6.00), P = 0.0433). On the opposite, the "on-land" group showed a better improvement of the Functional Ambulation Classification score (1.0 (0.75, 1.0) vs. 1.0 (1.0, 2.0), P = 0.0386). Aquatic physiotherapy showed an effect comparable to the land-based rehabilitation on gait and balance dysfunctions of neuropathic patients.

A randomised, placebo-controlled trial assessing the efficacy of an oral B group vitamin in preventing the development of chemotherapy-induced peripheral neuropathy (CIPN).

PubMed

Schloss, Janet M; Colosimo, Maree; Airey, Caroline; Masci, Paul; Linnane, Anthony W; Vitetta, Luis

2017-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect resulting from neurotoxic chemotherapeutic agents. This study aimed to assess the efficacy and safety of an oral B group vitamin compared to placebo, in preventing the incidence of CIPN in cancer patients undergoing neurotoxic chemotherapy. A pilot, randomised, placebo-controlled trial was conducted. Newly diagnosed cancer patients prescribed with taxanes, oxaliplatin or vincristine were invited to participate. A total of 71 participants (female 68 %, male 32 %) were enrolled into the study and randomised to the B group vitamin (n = 38) arm or placebo (n = 33). The data from 47 participants were eligible for analysis (B group vitamins n = 27, placebo n = 22). The primary outcome measure was the total neuropathy score assessed by an independent neurologist. Secondary outcome measures included serum vitamin B levels, quality of life, pain inventory and the patient neurotoxicity questionnaires. Outcome measures were conducted at baseline, 12, 24 and 36 weeks. The total neuropathy score (TNS) demonstrated that a B group vitamin did not significantly reduce the incidence of CIPN compared to placebo (p = 0.73). Statistical significance was achieved for patient perceived sensory peripheral neuropathy (12 weeks p = 0.03; 24 weeks p = 0.005; 36 weeks p = 0.021). The risk estimate for the Patient Neurotoxicity Questionnaire (PNQ) was also statistically significant (OR = 5.78, 95 % CI = 1.63-20.5). The European Organisation of Research and Treatment of Cancer (EORTC) quality of life, total pain score and pain interference showed no significance (p = 0.46, p = 0.9, p = 0.37 respectively). A trend was observed indicating that vitamin B12 may reduce the onset and severity of CIPN. An oral B group vitamin as an adjunct to neurotoxic chemotherapy regimens was not superior to placebo (p > 0.05) for the prevention of CIPN. Patients taking the B group vitamin perceived a

The influence of peripheral neuropathy, gender, and obesity on the postural stability of patients with type 2 diabetes mellitus.

PubMed

Herrera-Rangel, Aline; Aranda-Moreno, Catalina; Mantilla-Ochoa, Teresa; Zainos-Saucedo, Lylia; Jáuregui-Renaud, Kathrine

2014-01-01

To assess the influence of peripheral neuropathy, gender, and obesity on the postural stability of patients with type 2 diabetes mellitus. 151 patients with no history of otology, neurology, or orthopaedic or balance disorders accepted to participate in the study. After a clinical interview and neuropathy assessment, postural stability was evaluated by static posturography (eyes open/closed on hard/soft surface) and the "Up & Go" test. During static posturography, on hard surface, the length of sway was related to peripheral neuropathy, gender, age, and obesity; on soft surface, the length of sway was related to peripheral neuropathy, gender, and age, the influence of neuropathy was larger in males than in females, and closing the eyes increased further the difference between genders. The mean time to perform the "Up & Go" test was 11.6 ± 2.2 sec, with influence of peripheral neuropathy, gender, and age. In order to preserve the control of static upright posture during conditions with deficient sensory input, male patients with type 2 diabetes mellitus with no history of balance disorders may be more vulnerable than females, and obesity may decrease the static postural control in both males and females.

ACUDIN - ACUpuncture and laser acupuncture for treatment of DIabetic peripheral Neuropathy: a randomized, placebo-controlled, partially double-blinded trial.

PubMed

Meyer-Hamme, Gesa; Friedemann, Thomas; Greten, Henry Johannes; Plaetke, Rosemarie; Gerloff, Christian; Schroeder, Sven

2018-04-13

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus with significant clinical sequelae that can affect a patient's quality of life. Metabolic and microvascular factors are responsible for nerve damage, causing loss of nerve function, numbness, painful sensory symptoms, and muscle weakness. Therapy is limited to anti-convulsant or anti-depressant drugs for neuropathic pain and paresthesia. However, reduced sensation, balance and gait problems are insufficiently covered by this treatment. Previous data suggests that acupuncture, which has been in use in Traditional Chinese Medicine for many years, may potentially complement the treatment options for peripheral neuropathy. Nevertheless, more objective data on clinical outcome is necessary to generally recommend acupuncture to the public. We developed a study design for a prospective, randomized (RCT), placebo-controlled, partially double-blinded trial for investigating the effect of acupuncture on DPN as determined by nerve conduction studies (NCS) with the sural sensory nerve action potential amplitude as the primary outcome. The sural sensory nerve conduction velocity, tibial motor nerve action potential amplitude, tibial motor nerve conduction velocity, the neuropathy deficit score, neuropathy symptom score, and numeric rating scale questionnaires are defined as secondary outcomes. One hundred and eighty patients with type 2 diabetes mellitus will be randomized into three groups (needle acupuncture, verum laser acupuncture, and placebo laser acupuncture). We hypothesize that needle and laser acupuncture have beneficial effects on electrophysiological parameters and clinical and subjective symptoms in relation to DPN in comparison with placebo. The ACUDIN trial aims at investigating whether classical needle acupuncture and/or laser acupuncture are efficacious in the treatment of DPN. For the purpose of an objective parameter, NCS were chosen as outcome measures. Acupuncture

Exosomes derived from high-glucose-stimulated Schwann cells promote development of diabetic peripheral neuropathy.

PubMed

Jia, Longfei; Chopp, Michael; Wang, Lei; Lu, Xuerong; Szalad, Alexandra; Zhang, Zheng Gang

2018-06-22

Schwann cells actively interact with axons of dorsal root ganglia (DRG) neurons. Exosomes mediate intercellular communication by transferring their biomaterials, including microRNAs (miRs) into recipient cells. We hypothesized that exosomes derived from Schwann cells stimulated by high glucose (HG) exosomes accelerate development of diabetic peripheral neuropathy and that exosomal cargo miRs contribute to this process. We found that HG exosomes contained high levels of miR-28, -31a, and -130a compared to exosomes derived from non-HG-stimulated Schwann cells. In vitro, treatment of distal axons with HG exosomes resulted in reduction of axonal growth, which was associated with elevation of miR-28, -31a, and -130a and reduction of their target proteins of DNA methyltransferase-3α, NUMB (an endocytic adaptor protein), synaptosome associated protein 25, and growth-associated protein-43 in axons. In vivo, administration of HG exosomes to sciatic nerves of diabetic db/db mice at 7 wk of age promoted occurrence of peripheral neuropathy characterized by impairment of nerve conduction velocity and induction of mechanic and thermal hypoesthesia, which was associated with substantial decreases in intraepidermal nerve fibers. Our findings demonstrate a functional role of exosomes derived from HG-stimulated Schwann cells in mediating development of diabetic peripheral neuropathy.-Jia, L., Chopp, M., Wang, L., Lu, X., Szalad, A., Zhang, Z. G. Exosomes derived from high-glucose-stimulated Schwann cells promote development of diabetic peripheral neuropathy.

Electronic versus paper-pencil methods for assessing chemotherapy-induced peripheral neuropathy.

PubMed

Knoerl, Robert; Gray, Evan; Stricker, Carrie; Mitchell, Sandra A; Kippe, Kelsey; Smith, Gloria; Dudley, William N; Lavoie Smith, Ellen M

2017-11-01

The aim of this study is to examine and compare with the validated, paper/pencil European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy Scale (QLQ-CIPN20), the psychometric properties of three electronically administered patient reported outcome (PRO) measures of chemotherapy-induced peripheral neuropathy (CIPN): (1) the two neuropathy items from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), (2) the QLQ-CIPN20, and (3) the 0-10 Neuropathy Screening Question (NSQ). We employed a descriptive, cross-sectional design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy at an academic hospital. Participants completed the paper/pencil QLQ-CIPN20 and electronic versions of the QLQ-CIPN20, PRO-CTCAE, and NSQ. Internal consistency reliability, intraclass correlation, and concurrent and discriminant validity analyses were conducted. The alpha coefficients for the electronic QLQ-CIPN20 sensory and motor subscales were 0.76 and 0.75. Comparison of the electronic and paper/pencil QLQ-CIPN20 subscales supported mode equivalence (intraclass correlation range >0.91). Participants who reported the presence of numbness/tingling via the single-item NSQ reported higher mean QLQ-CIPN20 sensory subscale scores (p < 0.001). PRO-CTCAE neuropathy severity and interference items correlated well with the QLQ-CIPN20 electronic and paper/pencil sensory (r = 0.76; r = 0.70) and motor (r = 0.55; r = 0.62) subscales, and with the NSQ (r = 0.72; r = 0.44). These data support the validity of the electronically administered PRO-CTCAE neuropathy items, NSQ, and QLQ-CIPN20 for neuropathy screening in clinical practice. The electronic and paper/pencil versions of the QLQ-CIPN can be used interchangeably based on evidence of mode equivalence.

Self-Reported Physical Activity Using the International Physical Activity Questionnaire (IPAQ) in Australian Adults with Type 2 Diabetes, with and Without Peripheral Neuropathy.

PubMed

Nolan, Rebecca C; Raynor, Annette J; Berry, Narelle M; May, Esther J

2016-12-01

The aim of this study was to survey the level of self-reported physical activity in people with type 2 diabetes, with and without peripheral neuropathy. A sample of South Australian adults (n=481) 33 to 88 years of age who had type 2 diabetes, including 55 people with peripheral neuropathy, completed the International Physical Activity Questionnaire (IPAQ). Levels of self-reported physical activity were compared between those with and without peripheral neuropathy. People with type 2 diabetes and peripheral neuropathy (median [Mdn]=1433; interquartile range [IQR]=495 to 3390 metabolic equivalent minutes per week [MET-min/wk]) were less physically active than those without peripheral neuropathy (Mdn=2106; IQR=876 to 4380 MET-min/wk) (p=0.04). A total of 49% of people with type 2 diabetes and peripheral neuropathy met physical activity recommendations of 150 minutes of at least moderate activity per week, compared to 57% of people with type 2 diabetes alone. These findings demonstrate that people with type 2 diabetes and peripheral neuropathy reported being significantly less active than people with type 2 diabetes alone. People with type 2 diabetes and peripheral neuropathy need to be encouraged to perform higher levels of physical activity for biologic, physical and psychological benefits. Further studies using objective measures of physical activity are required to support these results. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Association of peripheral neuropathy with circulating advanced glycation end products, soluble receptor for advanced glycation end products and other risk factors in patients with type 2 diabetes.

PubMed

Aubert, C E; Michel, P-L; Gillery, P; Jaisson, S; Fonfrede, M; Morel, F; Hartemann, A; Bourron, O

2014-11-01

The pathogenesis of diabetic peripheral neuropathy remains uncertain and nonenzymatic glycoxidation is one of the contributing mechanisms. The aim of this study was to assess the respective relationship of diabetic peripheral neuropathy with glycoxidation, compared with other identified risk factors, in patients with type 2 diabetes. We included 198 patients with type 2 diabetes and high risk for vascular complications. Circulating concentrations of three advanced glycation end products (carboxymethyllysine, methyl-glyoxal-hydroimidazolone-1, pentosidine) and of their soluble receptor (sRAGE) were measured. Peripheral neuropathy was assessed by the neuropathy disability score and by the monofilament test and defined as either an abnormal monofilament test and/or a neuropathy disability score ≥6. Multivariate regression analyses were performed adjusting for potential confounding factors for neuropathy: age, gender, diabetes duration, current smoking, systolic blood pressure, waist circumference, height, peripheral arterial occlusive disease, glycated haemoglobin, estimated glomerular filtration rate and lipid profile. Prevalence of peripheral neuropathy was 20.7%. sRAGE and carboxymethyllysine were independently and positively associated with the presence of peripheral neuropathy. No significant association was found between peripheral neuropathy and methyl-glyoxal-hydroimidazolone-1 or pentosidine. Waist circumference, height and peripheral arterial occlusive disease were independently associated with peripheral neuropathy. Carboxymethyllysine and sRAGE were independently associated with peripheral neuropathy in patients with type 2 diabetes. Although the conclusions are limited by the absence of a healthy control population, this study confirms the relationship between advanced glycoxidation and diabetic peripheral neuropathy, independently of other risk factors. Copyright © 2014 John Wiley & Sons, Ltd.

Easier operation and similar power of 10 g monofilament test for screening diabetic peripheral neuropathy.

PubMed

Zhang, Qi; Yi, Na; Liu, Siying; Zheng, Hangping; Qiao, Xiaona; Xiong, Qian; Liu, Xiaoxia; Zhang, Shuo; Wen, Jie; Ye, Hongying; Zhou, Linuo; Li, Yiming; Hu, Renming; Lu, Bin

2018-01-01

Objective The 10 g Semmes-Weinstein monofilament evaluation (SWME) of 4 sites on each foot is recommended for distal symmetric polyneuropathy screening and diagnosis. A similar method has been proposed to diagnose 'high-risk' (for ulceration) feet, using 3 sites per foot. This study compared the effectiveness of SWME for testing 3, 4 and 10 sites per foot to identify patients with diabetic neuropathy. Methods We included 3497 subjects in a SWME of 10 sites; records from the 10-site SWME were used for a SWME of 3 and 4 sites. Neuropathy symptom scores and neuropathy deficit scores were evaluated to identify patients with diabetic peripheral neuropathy. Results The sensitivities of the 10 g SWME for 3, 4 and 10 sites were 17.8%, 19.0% and 22.4%, respectively. The Kappa coefficients for the SWME tests of 3, 4 and 10 sites were high (range: 0.78-0.93). Conclusions There were no significant differences in the effectiveness of 3-, 4- and 10-site SWME testing for diabetic peripheral neuropathy screening. SWME testing of 3 sites on each foot may be sufficient to screen for diabetic neuropathy.

Utility of quantitative sensory testing and screening tools in identifying HIV-associated peripheral neuropathy in Western Kenya: pilot testing.

PubMed

Cettomai, Deanna; Kwasa, Judith; Kendi, Caroline; Birbeck, Gretchen L; Price, Richard W; Bukusi, Elizabeth A; Cohen, Craig R; Meyer, Ana-Claire

2010-12-08

Neuropathy is the most common neurologic complication of HIV but is widely under-diagnosed in resource-constrained settings. We aimed to identify tools that accurately distinguish individuals with moderate/severe peripheral neuropathy and can be administered by non-physician healthcare workers (HCW) in resource-constrained settings. We enrolled a convenience sample of 30 HIV-infected outpatients from a Kenyan HIV-care clinic. A HCW administered the Neuropathy Severity Score (NSS), Single Question Neuropathy Screen (Single-QNS), Subjective Peripheral Neuropathy Screen (Subjective-PNS), and Brief Peripheral Neuropathy Screen (Brief-PNS). Monofilament, graduated tuning fork, and two-point discrimination examinations were performed. Tools were validated against a neurologist's clinical assessment of moderate/severe neuropathy. The sample was 57% male, mean age 38.6 years, and mean CD4 count 324 cells/µL. Neurologist's assessment identified 20% (6/30) with moderate/severe neuropathy. Diagnostic utilities for moderate/severe neuropathy were: Single-QNS--83% sensitivity, 71% specificity; Subjective-PNS-total--83% sensitivity, 83% specificity; Subjective-PNS-max and NSS--67% sensitivity, 92% specificity; Brief-PNS--0% sensitivity, 92% specificity; monofilament--100% sensitivity, 88% specificity; graduated tuning fork--83% sensitivity, 88% specificity; two-point discrimination--75% sensitivity, 58% specificity. Pilot testing suggests Single-QNS, Subjective-PNS, and monofilament examination accurately identify HIV-infected patients with moderate/severe neuropathy and may be useful diagnostic tools in resource-constrained settings.

Immune deficiency in mouse models for inherited peripheral neuropathies leads to improved myelin maintenance.

PubMed

Schmid, C D; Stienekemeier, M; Oehen, S; Bootz, F; Zielasek, J; Gold, R; Toyka, K V; Schachner, M; Martini, R

2000-01-15

The adhesive cell surface molecule P(0) is the most abundant glycoprotein in peripheral nerve myelin and fulfills pivotal functions during myelin formation and maintenance. Mutations in the corresponding gene cause hereditary demyelinating neuropathies. In mice heterozygously deficient in P(0) (P(0)(+/-) mice), an established animal model for a subtype of hereditary neuropathies, T-lymphocytes are present in the demyelinating nerves. To monitor the possible involvement of the immune system in myelin pathology, we cross-bred P(0)(+/-) mice with null mutants for the recombination activating gene 1 (RAG-1) or with mice deficient in the T-cell receptor alpha-subunit. We found that in P(0)(+/-) mice myelin degeneration and impairment of nerve conduction properties is less severe when the immune system is deficient. Moreover, isolated T-lymphocytes from P(0)(+/-) mice show enhanced reactivity to myelin components of the peripheral nerve, such as P(0), P(2), and myelin basic protein. We hypothesize that autoreactive immune cells can significantly foster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy.

Foot Kinetics and Kinematics Profile in Type 2 Diabetes Mellitus with Peripheral Neuropathy: A Hospital Based Study from South India.

PubMed

Hazari, Animesh; Maiya, Arun G; N, Shivashankara K

2018-02-01

A kinetic change in thefoot like altered plantar pressure is the most common etiological risk factor for causing foot ulcers among people with diabetes mellitus. Kinematic alterations in joint angle and spatiotemporal parameters of the gait have also been frequently observed in participants with diabetes peripheral neuropathy. Diabetes peripheral neuropathy is the most common long-term standing complication of type 2 diabetes mellitus. It leads to various micro and macrovascular related complication of the foot. There is a gap in theliteraturefor biomechanical evaluation and assessment in type 2 diabetes mellitus with peripheral neuropathy in Indian population. The aim of the study was to assess and determine the biomechanical changes including kinetics and kinematics of foot among diabetic peripheral neuropathy. The cross-sectional study was conducted at Diabetic Foot Clinic, Kasturba Hospital, Manipal University, Manipal, Karnataka, India. A total of 120 participants with type 2 diabetes mellitus and peripheral neuropathywere recruited under the purposive sampling method. Participants with any active ulceration or amputation were excluded from the study. The mean age, height, weight, body mass index, duration of diabetes was 57±14 year, 164±11cm, 61±18kg, 24± 3, 12±7 year respectively. There were significant changes in overall biomechanical profile along with clinical manifestations of diabetes peripheral neuropathy.The regression analysis showed statistical significance for dynamic maximum plantar pressure at forefoot with age, weight, height, duration of diabetes, body mass index, knee & ankle joint angle at toe-off phase of gait cycle,pinprick sensation and ankle reflex (R=.71,R =.55, F (12, 108)=521.9 kPa, p=.002) Conclusions: From the present study, we conclude that people with type 2 diabetes mellitus and peripheral neuropathy have significant changes in their foot kinetics and kinematicsparameters. Therefore, they could be at higher risk of foot

Investigation of the vitamin B12 deficiency with peripheral neuropathy in patients with type 2 diabetes mellitus treated using metformin.

PubMed

Olt, Serdar; Oznas, Orhan

2017-01-01

The relationship between vitamin B12 deficiency and peripheral neuropathy has been shown in a number of previous studies. Metformin is the indispensable first-line treatment for type 2 diabetes mellitus (DM) worldwide. One of the adverse effects of the use of metformin is vitamin B12 deficiency. In the present study, we investigated the relationship between vitamin B12 deficiency and peripheral neuropathy due to the use of metformin. Patient's laboratory and electromyography (EMG) data were retrospectively reviewed. Patients with no EMG report and other necessary information were excluded from the study. Eighty-six patients with type 2 DM using metformin were included in the study. Of these patients, 26 were males and 60 were females. The mean age of the patients was 55.1±7.7 years. The mean body mass index of the patients was 29.1±9.01 kg/m 2 . The mean HbA1c level of the patients was 8.6%±2.1%. The mean duration of diabetes was 8.02±5.4 years. The incidence of vitamin B12 deficiency was 38.4%. Peripheral neuropathy was detected in 33.7% patients. There was no statistically significant difference in vitamin B12 levels between patients with peripheral neuropathy and those without peripheral neuropathy (p=0.64). Therefore, it can be concluded that the lack of vitamin B12 secondary to the use of metformin did not significantly increase the frequency of peripheral neuropathy.

An inherited genetic variant in CEP72 promoter predisposes to vincristine-induced peripheral neuropathy in adults with acute lymphoblastic leukemia

PubMed Central

Stock, Wendy; Diouf, Barthelemy; Crews, Kristine R.; Pei, Deqing; Cheng, Cheng; Laumann, Kristina; Mandrekar, Sumithra J.; Luger, Selina; Advani, Anjali; Stone, Richard M.; Larson, Richard A.; Evans, William E.

2016-01-01

Peripheral neuropathy is a major toxicity of vincristine, yet no strategies exist for identifying at-risk adult patients. We used a case-control design of 48 adults receiving protocol therapy for acute lymphoblastic leukemia (ALL) who developed vincristine-induced neuropathy (NCI Grade 2-4) during treatment, and 48 matched controls who did not develop grade 2-4 neuropathy. Peripheral neuropathy was prospectively graded by NCI criteria. CEP72 promoter genotype (rs924607) was determined using PCR based SNP genotyping. Frequency of the CEP72 T/T genotype was higher in cases (31% vs 10%, p=0.0221) and the incidence of vincristine-induced neuropathy (grades 2-4) was significantly higher in patients homozygous for the CEP72 T/T genotype. 75% of the 20 patients homozygous for the CEP72 T allele developed grade 2-4 neuropathy, compared to 44% of patients with CEP72 CC or CT genotype (p=0.0221). The CEP72 polymorphism can identify adults at increased risk of vincristine-induced peripheral neuropathy. PMID:27618250

Inhibition of miR-25 aggravates diabetic peripheral neuropathy.

PubMed

Zhang, Yanzhuo; Song, Chunyu; Liu, Jing; Bi, Yonghong; Li, Hao

2018-06-05

The hyperglycemia-induced enhanced oxidative stress is a key factor of diabetic peripheral neuropathy implicated in the pathogenesis of diabetic neuropathy, and microRNA may be involved, playing promotion or protection roles. In this study, we aimed to investigate the function of miR-25 during the development of oxidative/nitrative stress and in subsequent neurological problems. We detected the oxidative stress effects and expression of miR-25 on sciatic nerves from db/db diabetic model mice and analyzed the expression of related genes by qPCR and Western blotting. Interestingly, we observed increased reactive oxygen species (ROS) and Nox4 expression in db/db mice accompanied with reduced miR-25. MiR-25 inhibitor treatment increased nicotinamide adenine dinucleotide phosphate activity in Schwann cells, whereas miR-25 precursor overexpression led to opposite results. MiR-25 precursor reduced the activation of protein kinase C and decreased Nox4 expression at both mRNA and protein levels. Advanced glycation endproducts (AGEs) and the receptor for advanced glycation endproducts (RAGE) were increased in the serum and in the peripheral nerves obtained from diabetic mice, and miR-25 inhibitor treatment in Schwann cells from wt mice led to the same effect. However, miR-25 precursor transfection reduced AGEs and RAGE, and further reduced inflammatory factors that contribute to the pathological process of peripheral nerves. These findings, for the first time, indicate that miR-25 acts as a protection factor in diabetic neuropathy by downregulating AGE-RAGE and reducing nicotinamide adenine dinucleotide phosphate oxidase. miR-25 reduced protein kinase C-α phosphorylation to produce less reactive oxygen species in diabetic peripheral nerves, and therefore it played an important role in the regulation of oxidative/nitrative stress and in consequent neurological dysfunction.This is an open-access article distributed under the terms of the Creative Commons Attribution

Dose Titration of Pregabalin in Patients with Painful Diabetic Peripheral Neuropathy: Simulation Based on Observational Study Patients Enriched with Data from Randomized Studies.

PubMed

Alexander, Joe; Edwards, Roger A; Manca, Luigi; Grugni, Roberto; Bonfanti, Gianluca; Emir, Birol; Whalen, Edward; Watt, Stephen; Parsons, Bruce

2018-03-01

Achieving a therapeutic response to pregabalin in patients with painful diabetic peripheral neuropathy (pDPN) requires adequate upward dose titration. Our goal was to identify relationships between titration and response to pregabalin in patients with pDPN. Data were integrated from nine randomized, placebo-controlled clinical trials as well as one 6-week open-label observational study conducted by 5808 physicians (2642 patients with pDPN) in standard outpatient settings in Germany. These studies evaluated pregabalin for treatment of pDPN. Using these data, we examined "what if" scenarios using a microsimulation platform that integrates data from randomized and observational sources as well as autoregressive-moving-average with exogenous inputs models that predict pain outcomes, taking into account weekly changes in pain, sleep interference, dose, and other patient characteristics that were unchanging. Final pain levels were significantly different depending on dose changes (P < 0.0001), with greater proportions improving with upward titration regardless of baseline pain severity. Altogether, 78.5% of patients with pDPN had 0-1 dose change, and 15.2% had ≥ 2 dose changes. Simulation demonstrated that the 4.8% of inadequately titrated patients who did not improve/very much improve their pain levels would have benefited from ≥ 2 dose changes. Patient satisfaction with tolerability (range 90.3-96.2%) was similar, regardless of baseline pain severity, number of titrations, or extent of improvement, suggesting that tolerability did not influence treatment response patterns. Upward dose titration reduced pain in patients with pDPN who actually received it. Simulation also predicted pain reduction in an inadequately titrated nonresponder subgroup of patients had they actually received adequate titration. The decision not to uptitrate must have been driven by factors other than tolerability. Pfizer, Inc.

Association of aldose reductase gene polymorphism (C-106T) in susceptibility of diabetic peripheral neuropathy among north Indian population.

PubMed

Gupta, Balram; Singh, S K

2017-07-01

Polymorphism in aldose reductase (ALR) gene at nucleotide C(-106)T (rs759853) in the promoter region is associated with susceptibility to development of diabetic peripheral neuropathy. The aim of this study was to detect the association of the C (-106)T polymorphism of ALR gene and its frequency among patients with type 2 diabetes mellitus with and without peripheral neuropathy. The study subjects were divided into three groups. Group I included 356 patients with diabetes having peripheral neuropathy. Group II included 294 patients with diabetes without peripheral neuropathy and group III included 181 healthy subjects. Genotyping of ALR C(-106)T SNPs was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods. The genetic risk among the groups was compared and tested by calculating odds ratio with 95% class interval. ALR 106TT genotype was significantly higher in group I compared to group II with an odds ratio of 2.12 (95% CI: 1.22-3.67; p<0.01). Recessive model (CC+CT vs. TT), as well as T allele distribution also showed significant association to develop neuropathy with relative risk of 1.97 (95% CI: 1.16-3.35; p<0.01) and 1.36 (95% CI: 1.07-1.72; p=0.01) respectively. In conclusion, the ALR C-106T polymorphism was associated with higher risk of peripheral neuropathy in patients with type 2 diabetes mellitus. Copyright © 2017 Elsevier Inc. All rights reserved.

Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort

PubMed Central

Shah, Arya; Hoffman, E. Matthew; Mauermann, Michelle L; Loprinzi, Charles L; Windebank, Anthony J; Klein, Christopher J; Staff, Nathan P

2018-01-01

OBJECTIVE To assess disease burden of chemotherapy-induced peripheral neuropathy (CIPN), which is a common dose-limiting side-effect of neurotoxic chemotherapy. Late effects of CIPN may increase with improved cancer survival. METHODS Olmsted County, Minnesota residents receiving neurotoxic chemotherapy were identified and CIPN was ascertained via text searches of polyneuropathy symptoms in the medical record. Clinical records were queried to collect data on baseline characteristics, risk factors, signs and symptoms of CIPN, medications, impairments, and ICD-9 diagnostic codes for all subjects. RESULTS A total of 509 individuals with incident exposure to an inclusive list of neurotoxic chemotherapy agents between 2006 and 2008 were identified. 268 (52.7%) of these individuals were determined to have CIPN. The median time from incident exposure to first documented symptoms was 71 days. Patients with CIPN received a neuropathy ICD-9 diagnosis in only 37 instances (13.8%). Pain symptoms and use of pain medications were observed more often in patients with CIPN. 5-year survival was greater in those with CIPN (55.2%) versus those without (36.1%). Those with CIPN surviving greater than 5 years (n=145) continued to have substantial impairments and were more likely to be prescribed opioids than those without CIPN (OR 2.0, 1.06–3.69). CONCLUSIONS Results from our population-based study are consistent with previous reports of high incidence of CIPN in the first two years following incident exposure to neurotoxic chemotherapeutic agents, and its association with significant pain symptomatology and accompanied long-term opioid use. Increased survival following exposure to neurotoxic chemotherapy and its long-term disease burden necessitates further study of among survivors. PMID:29439162

Intravenous immunoglobulin for chronic residual peripheral neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a multicenter, double-blind trial.

PubMed

Koike, Haruki; Akiyama, Kazuo; Saito, Toyokazu; Sobue, Gen

2015-03-01

Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome, frequently affects the peripheral nervous system. We conducted a multicenter, double-blind, three-arm treatment period, randomized, pre-post trial to assess the efficacy of intravenous immunoglobulin (IVIg) administration for residual peripheral neuropathy in patients with EGPA that is in remission, indicated by laboratory indices. Twenty-three patients were randomly assigned into three groups, in which the timing of IVIg and placebo administration was different. Each group received one course of intervention and two courses of placebo at 2-week intervals. Treatment effects were assessed every 2 weeks for 8 weeks. The primary outcome measure, the amount of change in the manual muscle testing sum score 2 weeks after IVIg administration, significantly increased (p = 0.002). The results over time suggested that this effect continued until the last assessment was done 8 weeks later. The number of muscles with manual muscle testing scores of three or less (p = 0.004) and the neuropathic pain scores represented by the visual analogue scale (p = 0.005) also improved significantly 2 weeks after IVIg administration. This study indicates that IVIg treatment for EGPA patients with residual peripheral neuropathy should be considered even when laboratory indices suggest remission of the disease.

Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy.

PubMed

Ahmed, Marwan A; Muntingh, George; Rheeder, Paul

2016-10-07

The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients. In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency. Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman's rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3

High Prevalence and Incidence of Diabetic Peripheral Neuropathy in Children and Adolescents With Type 1 Diabetes Mellitus: Results From a Five-Year Prospective Cohort Study.

PubMed

Walter-Höliner, Isabella; Barbarini, Daniela Seick; Lütschg, Jürg; Blassnig-Ezeh, Anya; Zanier, Ulrike; Saely, Christoph H; Simma, Burkhard

2018-03-01

In this prospective cohort study, we investigated the prevalence of diabetic peripheral neuropathy at baseline and after five years of follow-up in children and adolescents with type 1 diabetes mellitus using both measurements of nerve conduction velocity and clinical neurological examination. A total of 38 patients who underwent insulin pump or intensive insulin therapy were included. The subjects averaged 12.6 ± 2.4 years of age and their diabetes duration averaged 5.6 ± 3.2 years. All patients underwent a detailed physical, neurological, and electrophysiological examination, as well as laboratory testing at their annual checkup. At baseline, the prevalence of diabetic peripheral neuropathy diagnosed using neurological examination was 13.2%, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 31.6%, highlighting a high prevalence of subclinical diabetic peripheral neuropathy. During follow-up, there was a strong increase in the prevalence of clinically diagnosed diabetic peripheral neuropathy, which reached 34.2% (P = 0.039) after five years; the proportion of patients with subclinical diabetic peripheral neuropathy even reached 63.2% (P = 0.002). The most significant changes in electrophysiological parameters were observed in the tibial sensory nerve (P = 0.001). The prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus was high, and there was a rapid increase in the prevalence of diabetic peripheral neuropathy during a five-year follow-up interval. Importantly, our data show that a mere clinical evaluation is not sensitive enough to diagnose diabetic peripheral neuropathy in these patients. Nerve conduction velocity measurement, which is regarded as the gold standard for the assessment of diabetic peripheral neuropathy, should be applied more broadly. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnostic Accuracy of Fall Risk Assessment Tools in People With Diabetic Peripheral Neuropathy

PubMed Central

Pohl, Patricia S.; Mahnken, Jonathan D.; Kluding, Patricia M.

2012-01-01

Background Diabetic peripheral neuropathy affects nearly half of individuals with diabetes and leads to increased fall risk. Evidence addressing fall risk assessment for these individuals is lacking. Objective The purpose of this study was to identify which of 4 functional mobility fall risk assessment tools best discriminates, in people with diabetic peripheral neuropathy, between recurrent “fallers” and those who are not recurrent fallers. Design A cross-sectional study was conducted. Setting The study was conducted in a medical research university setting. Participants The participants were a convenience sample of 36 individuals between 40 and 65 years of age with diabetic peripheral neuropathy. Measurements Fall history was assessed retrospectively and was the criterion standard. Fall risk was assessed using the Functional Reach Test, the Timed “Up & Go” Test, the Berg Balance Scale, and the Dynamic Gait Index. Sensitivity, specificity, positive and negative likelihood ratios, and overall diagnostic accuracy were calculated for each fall risk assessment tool. Receiver operating characteristic curves were used to estimate modified cutoff scores for each fall risk assessment tool; indexes then were recalculated. Results Ten of the 36 participants were classified as recurrent fallers. When traditional cutoff scores were used, the Dynamic Gait Index and Functional Reach Test demonstrated the highest sensitivity at only 30%; the Dynamic Gait Index also demonstrated the highest overall diagnostic accuracy. When modified cutoff scores were used, all tools demonstrated improved sensitivity (80% or 90%). Overall diagnostic accuracy improved for all tests except the Functional Reach Test; the Timed “Up & Go” Test demonstrated the highest diagnostic accuracy at 88.9%. Limitations The small sample size and retrospective fall history assessment were limitations of the study. Conclusions Modified cutoff scores improved diagnostic accuracy for 3 of 4 fall risk

Effectiveness of aquatic versus land physiotherapy in the treatment of peripheral neuropathies: a randomized controlled trial

PubMed Central

Zivi, Ilaria; Maffia, Sara; Ferrari, Vanessa; Zarucchi, Alessio; Molatore, Katia; Maestri, Roberto; Frazzitta, Giuseppe

2017-01-01

Objective: To compare the effects on gait and balance of aquatic physiotherapy versus on-land training, in the context of an inpatient rehabilitation treatment tailored for peripheral neuropathies. Design: Parallel-group, single-center, single-blind randomized controlled trial. Subjects and setting: Consecutive patients affected by peripheral neuropathy admitted in our Neuro-Rehabilitation Unit. Interventions: Patients received a four-week rehabilitation program composed by daily sessions of conventional physiotherapy and three sessions/week of specific treatment (aquatic vs. on-land). Main measures: Primary outcome measures were Berg Balance Scale and Dynamic Gait Index. Secondary outcome measures were Neuropathic Pain Scale, Overall Neuropathy Limitations Scale, Functional Independence Measure, Functional Ambulation Classification, Conley Scale and Medical Research Council Scale score for the strength of hip and ankle flexor and extensor muscles. For each scale, we calculated the difference between the scores at discharge and admission and compared it between the two groups. Results: Forty patients were enrolled: 21 in the water-based rehabilitation group and 19 in the land-based one. Patients were similar between groups. When comparing the groups, we found that “in-water” patients had a significant better improvement in the Dynamic Gait Index score (6.00 (4.00, 7.25) vs. 4.00 (1.25, 6.00), P = 0.0433). On the opposite, the “on-land” group showed a better improvement of the Functional Ambulation Classification score (1.0 (0.75, 1.0) vs. 1.0 (1.0, 2.0), P = 0.0386). Conclusion: Aquatic physiotherapy showed an effect comparable to the land-based rehabilitation on gait and balance dysfunctions of neuropathic patients. PMID:29232980

[Chemotherapy-induced peripheral neuropathies: an integrative review of the literature].

PubMed

Costa, Talita Cassanta; Lopes, Miriam; Anjos, Anna Cláudia Yokoyama Dos; Zago, Marcia Maria Fontão

2015-04-01

To identify scientific studies and to deepen the knowledge of peripheral neuropathies induced by chemotherapy antineoplastic, seeking evidence for assistance to cancer patients. Integrative review of the literature conducted in the databases Latin American and Caribbean Health Sciences (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis (PubMed/MEDLINE), the Cochrane Library and the Spanish Bibliographic Index Health Sciences (IBECS). The sample consisted of 15 studies published between 2005-2014 that met the inclusion criteria. Studies showed aspects related to advanced age, main symptoms of neuropathy and chemotherapy agents as important adverse effect of neuropathy. We identified a small number of studies that addressed the topic, as well as low production of evidence related to interventions with positive results. It is considered important to develop new studies proposed for the prevention and/or treatment, enabling adjustment of the patient's cancer chemotherapy and consequently better service.

Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes.

PubMed

Kandula, Tejaswi; Farrar, Michelle Anne; Cohn, Richard J; Mizrahi, David; Carey, Kate; Johnston, Karen; Kiernan, Matthew C; Krishnan, Arun V; Park, Susanna B

2018-05-14

In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors. To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations. In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation. Chemotherapy agents known to be toxic to peripheral nerves. The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures. Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion. Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 54 of 107 participants (50.5%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 μV; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient

Between genetics and biology. Is ENMG useful in peripheral neuropathy diagnosis and management?

PubMed

Stålberg, E

2016-10-01

Neurography and EMG are complementary techniques used in the diagnosis and monitoring of neuropathies. Both assess function of the peripheral nervous system and provide clinically useful information regarding the functional status of peripheral nerves. This information is not readily obtainable using biochemical, genetic or imaging techniques. I will discuss the role of these techniques in the diagnosis and management of neuropathies and some limitations of these techniques. These methods are routinely used in an EMG lab. These are most useful when used in conjunction with clinical examination to answer a well-defined clinical question. Reference values are required for interpretation of the data. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Peripheral neuropathy in diabetes: it's not always what it looks like.

PubMed

Maltese, G; Tan, S V; Bruno, E; Brackenridge, A; Thomas, S

2018-06-04

Hereditary Neuropathy with liability to Pressure Palsies (HNPP) is an autosomal dominant neuropathy, associated with deletion of the Peripheral Myelin Protein-22 (PMP-22) gene, causing recurrent painless palsies with age of onset between 10 and 30 years old. Only a few cases of Type 2 Diabetes and HNPP have been described and the coexistence of HNPP and Type 1 diabetes has never been reported. A 54-year old man with a history of Type 1 diabetes, managed with continuous subcutaneous insulin infusion (CSII), presented with deterioration of long-standing motor and sensory symptoms, previously attributed to golfer's elbow, diabetic neuropathy and spinal degenerative disease. He had multilevel severe spine degenerative changes and L4/L5 and L5/S1 root impingements with a L4/L5 discectomy performed when he was 25 years old. On physical examination he had normal power and distal hypoaesthesia of the digits and plantar aspect of the feet. Investigations revealed normal full blood count, liver and renal function, electrolytes, vitamin B12 and serum folate. He suffered from primary hypothyroidism and thyroid function tests indicated adequate levothyroxine replacement. Nerve conduction studies revealed a generalized demyelinating sensorimotor neuropathy, with more severe involvement of nerves over entrapment sites. Further history that his father suffered from episodes of weakness and numbness was elicited. Genetic analysis revealed one copy of the PMP22 gene at 17p11.2 confirming the diagnosis of HNPP. In people with diabetes the evaluation of peripheral neuropathy should include a careful history, a comprehensive physical examination, blood tests and in some cases nerve conduction studies and genetic testing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Improved sensitivity in patients with peripheral neuropathy: effects of monochromatic infrared photo energy.

PubMed

DeLellis, Salvatore L; Carnegie, Dale H; Burke, Thomas J

2005-01-01

The medical records of 1,047 patients (mean age, 73 years) with established peripheral neuropathy were examined to determine whether treatment with monochromatic infrared photo energy was associated with increased foot sensitivity to the 5.07 Semmes-Weinstein monofilament. The peripheral neuropathy in 790 of these patients (75%) was due to diabetes mellitus. Before treatment with monochromatic infrared photo energy, of the ten tested sites (five on each foot), a mean +/- SD of 7.9 +/- 2.4 sites were insensitive to the 5.07 Semmes-Weinstein monofilament, and 1,033 patients exhibited loss of protective sensation. After treatment, the mean +/- SD number of insensate sites on both feet was 2.3 +/- 2.4, an improvement of 71%. Only 453 of 1,033 patients (43.9%) continued to have loss of protective sensation after treatment. Therefore, monochromatic infrared photo energy treatment seems to be associated with significant clinical improvement in foot sensation in patients, primarily Medicare aged, with peripheral neuropathy. Because insensitivity to the 5.07 Semmes-Weinstein monofilament has been reported to be a major risk factor for diabetic foot wounds, the use of monochromatic infrared photo energy may be associated with a reduced incidence of diabetic foot wounds and amputations.

Vincristine-induced peripheral neuropathy in a neonate with congenital acute lymphoblastic leukemia.

PubMed

Baker, Steven K; Lipson, David M

2010-04-01

We report the case of a 46-day-old boy with a fulminant vincristine-induced peripheral neuropathy after treatment for congenital acute lymphoblastic leukemia. Flaccid paralysis developed at the end of the first phase of induction, requiring intubation and ventilation for 51 days. Treatment was initiated with levocarnitine, N-acetylcysteine, and pyridoxine and progressive reversal of the neuropathy occurred over the next 4 months. Potential differences in pathogenesis and presentation of vincristine neurotoxicity and Guillian-Barre syndrome in the neonate are discussed.

Investigation of the vitamin B12 deficiency with peripheral neuropathy in patients with type 2 diabetes mellitus treated using metformin

PubMed Central

Olt, Serdar; Oznas, Orhan

2017-01-01

OBJECTIVE: The relationship between vitamin B12 deficiency and peripheral neuropathy has been shown in a number of previous studies. Metformin is the indispensable first-line treatment for type 2 diabetes mellitus (DM) worldwide. One of the adverse effects of the use of metformin is vitamin B12 deficiency. In the present study, we investigated the relationship between vitamin B12 deficiency and peripheral neuropathy due to the use of metformin. METHODS: Patient’s laboratory and electromyography (EMG) data were retrospectively reviewed. Patients with no EMG report and other necessary information were excluded from the study. RESULTS: Eighty-six patients with type 2 DM using metformin were included in the study. Of these patients, 26 were males and 60 were females. The mean age of the patients was 55.1±7.7 years. The mean body mass index of the patients was 29.1±9.01 kg/m2. The mean HbA1c level of the patients was 8.6%±2.1%. The mean duration of diabetes was 8.02±5.4 years. The incidence of vitamin B12 deficiency was 38.4%. Peripheral neuropathy was detected in 33.7% patients. There was no statistically significant difference in vitamin B12 levels between patients with peripheral neuropathy and those without peripheral neuropathy (p=0.64). CONCLUSION: Therefore, it can be concluded that the lack of vitamin B12 secondary to the use of metformin did not significantly increase the frequency of peripheral neuropathy. PMID:29270571

Reversal of diabetic peripheral neuropathy with phototherapy (MIRE) decreases falls and the fear of falling and improves activities of daily living in seniors.

PubMed

Powell, Mark W; Carnegie, Dale H; Burke, Thomas J

2006-01-01

to determine whether restoration of sensation, impaired due to diabetic peripheral neuropathy (DPN), would reduce the number of falls and the fear of falling and improve activities of daily living (ADL) in a Medicare-aged population. retrospective cohort study of patients with documented, monochromatic near-infrared phototherapy (MIRE)-mediated, symptomatic reversal of DPN. responses to a health status questionnaire following symptomatic reversal of DPN. 252 patients (mean age 76 years) provided health information following symptomatic reversal of diabetic neuropathy (mean duration 8.6 months). incidence of falls and fear of falling decreased within 1 month after reversal of peripheral neuropathy and remained low after 1 year. Likewise, improved ADL were evident soon after reversal of peripheral neuropathy and showed further improvement after 1 year. Overall, reversal of peripheral neuropathy in a clinician's office and subsequent use of MIRE at home was associated with a 78% reduction in falls, a 79% decrease in balance-related fear of falling and a 72% increase in ADL (P < 0.0002 for all results). reversal of peripheral neuropathy is associated with an immediate reduction in the absolute number of falls, a reduced fear of falling and improved ADL. These results suggest that symptomatic reversal of diabetic neuropathy will have a substantial favourable, long-term socioeconomic impact on patients with DPN and the Medicare system, and improve the quality of life for elderly patients with diabetes and peripheral neuropathy.

Role of Complement in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy.

PubMed

Xu, Jijun; Zhang, Lingjun; Xie, Mian; Li, Yan; Huang, Ping; Saunders, Thomas L; Fox, David A; Rosenquist, Richard; Lin, Feng

2018-06-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a painful and debilitating side effect of cancer chemotherapy with an unclear pathogenesis. Consequently, the available therapies for this neuropathic pain syndrome are inadequate, leading to a significantly reduced quality of life in many patients. Complement, a key component of the innate immune system, has been associated with neuroinflammation, a potentially important trigger of some types of neuropathic pain. However, the role of complement in CIPN remains unclear. To address this issue, we developed a C3 knockout (KO) rat model and induced CIPN in these KO rats and wild-type littermates via the i.p. administration of paclitaxel, a chemotherapeutic agent associated with CIPN. We then compared the severity of mechanical allodynia, complement activation, and intradermal nerve fiber loss between the groups. We found that 1) i.p. paclitaxel administration activated complement in wild-type rats, 2) paclitaxel-induced mechanical allodynia was significantly reduced in C3 KO rats, and 3) the paclitaxel-induced loss of intradermal nerve fibers was markedly attenuated in C3 KO rats. In in vitro studies, we found that paclitaxel-treated rat neuronal cells activated complement, leading to cellular injury. Our findings demonstrate a previously unknown but pivotal role of complement in CIPN and suggest that complement may be a new target for the development of novel therapeutics to manage this painful disease. Copyright © 2018 by The American Association of Immunologists, Inc.

Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Nudelman, Kelly N H; McDonald, Brenna C; Wang, Yang; Smith, Dori J; West, John D; O'Neill, Darren P; Zanville, Noah R; Champion, Victoria L; Schneider, Bryan P; Saykin, Andrew J

2016-03-01

To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment-related brain structural changes. Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray

Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Nudelman, Kelly N.H.; McDonald, Brenna C.; Wang, Yang; Smith, Dori J.; West, John D.; O'Neill, Darren P.; Zanville, Noah R.; Champion, Victoria L.; Schneider, Bryan P.

2016-01-01

Purpose To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment–related brain structural changes. Methods Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. Results Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P < .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P = .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P < .001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P < .005). Conclusion Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with

Diagnostic capability of retinal thickness measures in diabetic peripheral neuropathy.

PubMed

Srinivasan, Sangeetha; Pritchard, Nicola; Sampson, Geoff P; Edwards, Katie; Vagenas, Dimitrios; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

To examine the diagnostic capability of the full retinal and inner retinal thickness measures in differentiating individuals with diabetic peripheral neuropathy (DPN) from those without neuropathy and non-diabetic controls. Individuals with (n=44) and without (n=107) diabetic neuropathy and non-diabetic control (n=42) participants underwent spectral domain optical coherence tomography (SDOCT). Retinal thickness in the central 1mm zone (including the fovea), parafovea and perifovea was assessed in addition to ganglion cell complex (GCC) global loss volume (GCC GLV) and focal loss volume (GCC FLV), and retinal nerve fiber layer (RNFL) thickness. Diabetic neuropathy was defined using a modified neuropathy disability score (NDS) recorded on a 0-10 scale, wherein, NDS ≥3 indicated neuropathy and NDS indicated <3 no neuropathy. Diagnostic performance was assessed by areas under the receiver operating characteristic curves (AUCs), 95 per cent confidence intervals (CI), sensitivities at fixed specificities, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and the cut-off points for the best AUCs obtained. The AUC for GCC FLV was 0.732 (95% CI: 0.624-0.840, p<0.001) with a sensitivity of 53% and specificity of 80% for differentiating DPN from controls. Evaluation of the LRs showed that GCC FLV was associated with only small effects on the post-test probability of the disease. The cut-off point calculated using the Youden index was 0.48% (67% sensitivity and 73% specificity) for GCC FLV. For distinguishing those with neuropathy from those without neuropathy, the AUCs of retinal parameters ranged from 0.508 for the central zone to 0.690 for the inferior RNFL thickness. For distinguishing those with moderate or advanced neuropathy from those with mild or no neuropathy, the inferior RNFL thickness demonstrated the highest AUC of 0.820, (95% CI: 0.731-0.909, p<0.001) with a sensitivity of 69% and 80% specificity. The cut-off-point for the inferior RNFL

Guidelines in the management of diabetic nerve pain: clinical utility of pregabalin

PubMed Central

Vinik, Aaron I; Casellini, Carolina M

2013-01-01

Diabetic peripheral neuropathy is a common complication of diabetes. It presents as a variety of syndromes for which there is no universally accepted unique classification. Sensorimotor polyneuropathy is the most common type, affecting about 30% of diabetic patients in hospital care and 25% of those in the community. Pain is the reason for 40% of patient visits in a primary care setting, and about 20% of these have had pain for greater than 6 months. Chronic pain may be nociceptive, which occurs as a result of disease or damage to tissue with no abnormality in the nervous system. In contrast, neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.” Persistent neuropathic pain interferes significantly with quality of life, impairing sleep and recreation; it also significantly impacts emotional well-being, and is associated with depression, anxiety, and noncompliance with treatment. Painful diabetic peripheral neuropathy is a difficult-to-manage clinical problem, and patients with this condition are more apt to seek medical attention than those with other types of diabetic neuropathy. Early recognition of psychological problems is critical to the management of pain, and physicians need to go beyond the management of pain per se if they are to achieve success. This evidence-based review of the assessment of the patient with pain in diabetes addresses the state-of-the-art management of pain, recognizing all the conditions that produce pain in diabetes and the evidence in support of a variety of treatments currently available. A search of the full Medline database for the last 10 years was conducted in August 2012 using the terms painful diabetic peripheral neuropathy, painful diabetic peripheral polyneuropathy, painful diabetic neuropathy and pain in diabetes. In addition, recent reviews addressing this issue were adopted as necessary. In particular, reports from the American Academy of

Guidelines in the management of diabetic nerve pain: clinical utility of pregabalin.

PubMed

Vinik, Aaron I; Casellini, Carolina M

2013-01-01

Diabetic peripheral neuropathy is a common complication of diabetes. It presents as a variety of syndromes for which there is no universally accepted unique classification. Sensorimotor polyneuropathy is the most common type, affecting about 30% of diabetic patients in hospital care and 25% of those in the community. Pain is the reason for 40% of patient visits in a primary care setting, and about 20% of these have had pain for greater than 6 months. Chronic pain may be nociceptive, which occurs as a result of disease or damage to tissue with no abnormality in the nervous system. In contrast, neuropathic pain is defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system." Persistent neuropathic pain interferes significantly with quality of life, impairing sleep and recreation; it also significantly impacts emotional well-being, and is associated with depression, anxiety, and noncompliance with treatment. Painful diabetic peripheral neuropathy is a difficult-to-manage clinical problem, and patients with this condition are more apt to seek medical attention than those with other types of diabetic neuropathy. Early recognition of psychological problems is critical to the management of pain, and physicians need to go beyond the management of pain per se if they are to achieve success. This evidence-based review of the assessment of the patient with pain in diabetes addresses the state-of-the-art management of pain, recognizing all the conditions that produce pain in diabetes and the evidence in support of a variety of treatments currently available. A search of the full Medline database for the last 10 years was conducted in August 2012 using the terms painful diabetic peripheral neuropathy, painful diabetic peripheral polyneuropathy, painful diabetic neuropathy and pain in diabetes. In addition, recent reviews addressing this issue were adopted as necessary. In particular, reports from the American Academy of Neurology

Acupuncture and Reflexology for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer

PubMed Central

Ben-Horin, Idan; Kahan, Peretz; Ryvo, Larisa; Inbar, Moshe; Lev-Ari, Shahar; Geva, Ravit

2017-01-01

Background: Treatment of chemotherapy-induced peripheral neuropathy (CIPN), which affects approximately 30% to 40% of patients treated with neuropathy-causing agents, is mainly symptomatic. Currently available interventions are of little benefit. Study Design: This study was conducted as a retrospective analysis of the efficacy of acupuncture and reflexology in alleviating CIPN in breast cancer patients. Methods: Medical records of 30 consecutive breast cancer patients who received both chemotherapy and treatment for CIPN according to our Acupuncture and Reflexology Treatment for Neuropathy (ART-N) protocol between 2011 and 2012 were reviewed. Symptom severity was rated at baseline, during, and after treatment. Results: The records of 30 breast cancer patients who had been concomitantly treated with chemotherapy and ART-N for CIPN were retrieved. Two records were incomplete, leaving a total of 28 patients who were enrolled into the study. Twenty patients (71%) had sensory neuropathy, 7 (25%) had motor neuropathy, and 1 (4%) had both sensory and motor neuropathy. Only 2 (10%) of the 20 patients with grades 1 to 2 neuropathy still reported symptoms at 12 months since starting the ART-N protocol. All 8 patients who presented with grades 3 to 4 neuropathy were symptom-free at the 12-month evaluation. Overall, 26 patients (93%) had complete resolution of CIPN symptoms. Conclusion: The results of this study demonstrated that a joint protocol of acupuncture and reflexology has a potential to improve symptoms of CIPN in breast cancer patients. The protocol should be validated on a larger cohort with a control group. It also warrants testing as a preventive intervention. PMID:28150504

Acupuncture and Reflexology for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer.

PubMed

Ben-Horin, Idan; Kahan, Peretz; Ryvo, Larisa; Inbar, Moshe; Lev-Ari, Shahar; Geva, Ravit

2017-09-01

Treatment of chemotherapy-induced peripheral neuropathy (CIPN), which affects approximately 30% to 40% of patients treated with neuropathy-causing agents, is mainly symptomatic. Currently available interventions are of little benefit. This study was conducted as a retrospective analysis of the efficacy of acupuncture and reflexology in alleviating CIPN in breast cancer patients. Medical records of 30 consecutive breast cancer patients who received both chemotherapy and treatment for CIPN according to our Acupuncture and Reflexology Treatment for Neuropathy (ART-N) protocol between 2011 and 2012 were reviewed. Symptom severity was rated at baseline, during, and after treatment. The records of 30 breast cancer patients who had been concomitantly treated with chemotherapy and ART-N for CIPN were retrieved. Two records were incomplete, leaving a total of 28 patients who were enrolled into the study. Twenty patients (71%) had sensory neuropathy, 7 (25%) had motor neuropathy, and 1 (4%) had both sensory and motor neuropathy. Only 2 (10%) of the 20 patients with grades 1 to 2 neuropathy still reported symptoms at 12 months since starting the ART-N protocol. All 8 patients who presented with grades 3 to 4 neuropathy were symptom-free at the 12-month evaluation. Overall, 26 patients (93%) had complete resolution of CIPN symptoms. The results of this study demonstrated that a joint protocol of acupuncture and reflexology has a potential to improve symptoms of CIPN in breast cancer patients. The protocol should be validated on a larger cohort with a control group. It also warrants testing as a preventive intervention.

Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source.

PubMed

Ma, Jiacheng; Kavelaars, Annemieke; Dougherty, Patrick M; Heijnen, Cobi J

2018-06-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting >60% of patients with cancer. Moreover, CIPN persists long into survivorship in approximately 20% to 30% of these patients. To the authors' knowledge, no drugs have been approved to date by the US Food and Drug Administration to effectively manage chemotherapy-induced neuropathic pain. The majority of the drugs tested for the management of CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious. The authors propose that there is a need to acquire a more thorough understanding of the etiology of CIPN so that effective, mechanism-based, disease-modifying interventions can be developed. It is important to note that such interventions should not interfere with the antitumor effects of chemotherapy. Mitochondria are rod-shaped cellular organelles that represent the powerhouses of the cell, in that they convert oxygen and nutrients into the cellular energy "currency" adenosine triphosphate. In addition, mitochondria regulate cell death. Neuronal mitochondrial dysfunction and the associated nitro-oxidative stress represent crucial final common pathways of CIPN. Herein, the authors discuss the potential to prevent or reverse CIPN by protecting mitochondria and/or inhibiting nitro-oxidative stress with novel potential drugs, including the mitochondrial protectant pifithrin-μ, histone deacetylase 6 inhibitors, metformin, antioxidants, peroxynitrite decomposition catalysts, and anti-inflammatory mediators including interleukin 10. This review hopefully will contribute toward bridging the gap between preclinical research and the development of realistic novel therapeutic strategies to prevent or reverse the devastating neurotoxic effects of chemotherapy on the (peripheral) nervous system. Cancer 2018;124:2289-98. © 2018 American Cancer Society. © 2018 American Cancer Society.

Pathophysiology of drug-induce peripheral neuropathy in patients with multiple myeloma.

PubMed

Luczkowska, K; Litwinska, Z; Paczkowska, E; Machalinski, B

2018-04-01

Multiple myeloma (MM) is a disease of unknown, complex etiology that affects primarily older adults. The course of the disease and the patients' survival time are very heterogeneous, but over the last decade, clear progress in the treatment of this incurable disease has been observed. Therapeutics that have proven to be highly effective include the immunomodulatory drug thalidomide and its newer analogs, lenalidomide and pomalidomide, as well as the proteasome inhibitors bortezomib and carfilzomib. However, the administration of some of the treatments, e.g., thalidomide or bortezomib, has also been associated with the occurrence of a serious and common adverse effect, drug-induced peripheral neuropathy. The mechanism of the development of the peripheral neuropathy is poorly understood. Nevertheless, one of its potential causes could be inadequate concentrations of crucial trophic factors, including neurotrophic and/or angiogenic factors, which are responsible for the proliferation, differentiation, survival and death of neuronal and nonneuronal cells.

Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy.

PubMed

Granovsky, Yelena; Nahman-Averbuch, Hadas; Khamaisi, Mogher; Granot, Michal

2017-05-01

Alleviation of pain, by either medical or surgical therapy, is accompanied by transition from less efficient, or pro-nociceptive, to efficient conditioned pain modulation (CPM). Spontaneous decrease or resolution of pain with disease progression is reported for some patients with painful diabetic neuropathy (PDN). To explore whether CPM changes similarly in parallel to spontaneous resolution of pain in PDN patients. In this cross-sectional study, thirty-three patients with PDN underwent psychophysical assessment of pain modulation on the forearm, remote from the clinical pain. Pain duration was not correlated with neuropathic pain intensity, yet, it correlated with CPM efficiency; patients with longer pain duration had same pain level, but more efficient CPM than those with short-pain duration (ρ = -0.417; P = 0.025, Spearman correlation). Patients with pain more than 2 years (median split) expressed efficient CPM that was not different from that of healthy controls. These patients also had lower temporal summation of pain than the short-pain duration patients group ( P < 0.05). The 2 patient groups did not differ in clinical pain characteristics or use of analgesics. Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to "normalize" with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN.

Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy

PubMed Central

Granovsky, Yelena; Nahman-Averbuch, Hadas; Khamaisi, Mogher; Granot, Michal

2017-01-01

Abstract Introduction: Alleviation of pain, by either medical or surgical therapy, is accompanied by transition from less efficient, or pro-nociceptive, to efficient conditioned pain modulation (CPM). Spontaneous decrease or resolution of pain with disease progression is reported for some patients with painful diabetic neuropathy (PDN). Objectives: To explore whether CPM changes similarly in parallel to spontaneous resolution of pain in PDN patients. Methods: In this cross-sectional study, thirty-three patients with PDN underwent psychophysical assessment of pain modulation on the forearm, remote from the clinical pain. Results: Pain duration was not correlated with neuropathic pain intensity, yet, it correlated with CPM efficiency; patients with longer pain duration had same pain level, but more efficient CPM than those with short-pain duration (ρ = −0.417; P = 0.025, Spearman correlation). Patients with pain more than 2 years (median split) expressed efficient CPM that was not different from that of healthy controls. These patients also had lower temporal summation of pain than the short-pain duration patients group (P < 0.05). The 2 patient groups did not differ in clinical pain characteristics or use of analgesics. Conclusion: Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to “normalize” with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN. PMID:29392208

Comorbidities and Risk of Chemotherapy-Induced Peripheral Neuropathy Among Participants 65 Years or Older in Southwest Oncology Group Clinical Trials

PubMed Central

Till, Cathee; Wright, Jason D.; Awad, Danielle; Ramsey, Scott D.; Barlow, William E.; Minasian, Lori M.; Unger, Joseph

2016-01-01

Background Neuropathy is a debilitating toxicity associated with various chemotherapy agents. We evaluated the association between common comorbid conditions and the development of peripheral neuropathy in patients treated with taxane-based chemotherapy. Methods We examined the Southwest Oncology Group database to identify phase II and III trials that included taxane therapy from 1999 to 2011. We linked the Southwest Oncology Group clinical records to Medicare claims data according to Social Security number, sex, and date of birth. The following disease conditions potentially associated with peripheral neuropathy were evaluated: diabetes, hypothyroidism, hypercholesterolemia, hypertension, varicella zoster, peripheral vascular disease, and autoimmune diseases. Multivariate logistic regression was used to model the odds of experiencing grade 2 to 4 neuropathy. Results A total of 1,401 patients from 23 studies were included in the analysis. Patients receiving paclitaxel were more likely to experience grade 2 to 4 neuropathy compared with docetaxel (25% v 12%, respectively; OR, 2.20; 95% CI, 1.52 to 3.18; P < .001). The inclusion of a platinum agent was also associated with greater neuropathy (OR, 1.68; 95% CI, 1.18 to 2.40; P = .004). For each increase in age of 1 year, the odds of neuropathy increased 4% (P = .006). Patients with complications from diabetes had more than twice the odds of having neuropathy (OR, 2.13; 95% CI, 1.31 to 3.46; P = .002) compared with patients with no diabetes. In contrast, patients with autoimmune disease were half as likely to experience neuropathy (OR, 0.49; 95% CI, 0.24 to 1.02; P = .06). The other conditions were not associated with neuropathy. Conclusion We found that in addition to drug-related factors, age and history of diabetes were independent predictors of the development of chemotherapy-induced peripheral neuropathy. Interestingly, we also observed that a history of autoimmune disease was associated with reduced odds of

Comorbidities and Risk of Chemotherapy-Induced Peripheral Neuropathy Among Participants 65 Years or Older in Southwest Oncology Group Clinical Trials.

PubMed

Hershman, Dawn L; Till, Cathee; Wright, Jason D; Awad, Danielle; Ramsey, Scott D; Barlow, William E; Minasian, Lori M; Unger, Joseph

2016-09-01

Neuropathy is a debilitating toxicity associated with various chemotherapy agents. We evaluated the association between common comorbid conditions and the development of peripheral neuropathy in patients treated with taxane-based chemotherapy. We examined the Southwest Oncology Group database to identify phase II and III trials that included taxane therapy from 1999 to 2011. We linked the Southwest Oncology Group clinical records to Medicare claims data according to Social Security number, sex, and date of birth. The following disease conditions potentially associated with peripheral neuropathy were evaluated: diabetes, hypothyroidism, hypercholesterolemia, hypertension, varicella zoster, peripheral vascular disease, and autoimmune diseases. Multivariate logistic regression was used to model the odds of experiencing grade 2 to 4 neuropathy. A total of 1,401 patients from 23 studies were included in the analysis. Patients receiving paclitaxel were more likely to experience grade 2 to 4 neuropathy compared with docetaxel (25% v 12%, respectively; OR, 2.20; 95% CI, 1.52 to 3.18; P < .001). The inclusion of a platinum agent was also associated with greater neuropathy (OR, 1.68; 95% CI, 1.18 to 2.40; P = .004). For each increase in age of 1 year, the odds of neuropathy increased 4% (P = .006). Patients with complications from diabetes had more than twice the odds of having neuropathy (OR, 2.13; 95% CI, 1.31 to 3.46; P = .002) compared with patients with no diabetes. In contrast, patients with autoimmune disease were half as likely to experience neuropathy (OR, 0.49; 95% CI, 0.24 to 1.02; P = .06). The other conditions were not associated with neuropathy. We found that in addition to drug-related factors, age and history of diabetes were independent predictors of the development of chemotherapy-induced peripheral neuropathy. Interestingly, we also observed that a history of autoimmune disease was associated with reduced odds of neuropathy. Patients with diabetic

Somatosensory evoked potentials in the assessment of peripheral neuropathies: Commented results of a survey among French-speaking practitioners and recommendations for practice.

PubMed

Morizot-Koutlidis, R; André-Obadia, N; Antoine, J-C; Attarian, S; Ayache, S S; Azabou, E; Benaderette, S; Camdessanché, J-P; Cassereau, J; Convers, P; d'Anglejean, J; Delval, A; Durand, M-C; Etard, O; Fayet, G; Fournier, E; Franques, J; Gavaret, M; Guehl, D; Guerit, J-M; Krim, E; Kubis, N; Lacour, A; Lozeron, P; Mauguière, F; Merle, P-E; Mesrati, F; Mutschler, V; Nicolas, G; Nordine, T; Pautot, V; Péréon, Y; Petiot, P; Pouget, J; Praline, J; Salhi, H; Trébuchon, A; Tyvaert, L; Vial, C; Zola, J-M; Zyss, J; Lefaucheur, J-P

2015-05-01

Somatosensory evoked potentials (SSEPs) are increasingly performed for the assessment of peripheral neuropathies, but no practical guidelines have yet been established in this specific application. To determine the relevant indication criteria and optimal technical parameters for SSEP recording in peripheral neuropathy investigation. A survey was conducted among the French-speaking practitioners with experience of SSEP recording in the context of peripheral neuropathies. The results of the survey were analyzed and discussed to provide recommendations for practice. SSEPs appear to be a second-line test when electroneuromyographic investigation is not sufficiently conclusive, providing complementary and valuable information on central and proximal peripheral conduction in the somatosensory pathways. Guidelines for a standardized recording protocol, including the various parameters to be measured, are proposed. We hope that these proposals will help to recognize the value of this technique in peripheral neuropathy assessment in clinical practice. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort.

PubMed

Shah, Arya; Hoffman, E Matthew; Mauermann, Michelle L; Loprinzi, Charles L; Windebank, Anthony J; Klein, Christopher J; Staff, Nathan P

2018-06-01

To assess disease burden of chemotherapy-induced peripheral neuropathy (CIPN), which is a common dose-limiting side effect of neurotoxic chemotherapy. Late effects of CIPN may increase with improved cancer survival. Olmsted County, Minnesota residents receiving neurotoxic chemotherapy were identified and CIPN was ascertained via text searches of polyneuropathy symptoms in the medical record. Clinical records were queried to collect data on baseline characteristics, risk factors, signs and symptoms of CIPN, medications, impairments and International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes for all subjects. A total of 509 individuals with incident exposure to an inclusive list of neurotoxic chemotherapy agents between 2006 and 2008 were identified. 268 (52.7%) of these individuals were determined to have CIPN. The median time from incident exposure to first documented symptoms was 71 days. Patients with CIPN received a neuropathy ICD-9 diagnosis in only 37 instances (13.8%). Pain symptoms and use of pain medications were observed more often in patients with CIPN. Five-year survival was greater in those with CIPN (55.2%) versus those without (36.1%). Those with CIPN surviving greater than 5 years (n=145) continued to have substantial impairments and were more likely to be prescribed opioids than those without CIPN (OR 2.0, 1.06-3.69). Results from our population-based study are consistent with previous reports of high incidence of CIPN in the first 2 years following incident exposure to neurotoxic chemotherapeutic agents, and its association with significant pain symptomatology and accompanied long-term opioid use. Increased survival following exposure to neurotoxic chemotherapy and its long-term disease burden necessitates further study among survivors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Transcobalamin 776C→G polymorphism is associated with peripheral neuropathy in elderly individuals with high folate intake.

PubMed

Sawaengsri, Hathairat; Bergethon, Peter R; Qiu, Wei Qiao; Scott, Tammy M; Jacques, Paul F; Selhub, Jacob; Paul, Ligi

2016-12-01

The 776C→G polymorphism of the vitamin B-12 transport protein transcobalamin gene (TCN2) (rs1801198; Pro259Arg) is associated with a lower holotranscobalamin concentration in plasma. This effect may reduce the availability of vitamin B-12 to tissues even when vitamin B-12 intake is adequate. Clinical outcomes associated with vitamin B-12 insufficiency could potentially be worsened by high folate intake. We determined the association of the TCN2 776C→G polymorphism and folate intake with peripheral neuropathy in elders with normal plasma concentrations of vitamin B-12. Participants in this cross-sectional study (n = 171) were from a cohort of community-based, home-bound elderly individuals aged ≥60 y who underwent an evaluation by physicians including an assessment for peripheral neuropathy. Participants were administered food-frequency and general health status questionnaires, anthropometric measurements were taken, and a fasting blood sample from each subject was collected. Odds of neuropathy were 3-fold higher for GG genotypes than for CC genotypes (OR: 3.33; 95% CI: 1.15, 9.64). When folate intake was >2 times the Recommended Dietary Allowance (800 μg), GG genotypes had 6.9-fold higher odds of neuropathy than CC genotypes (OR: 6.9; 95% CI: 1.31, 36.36). There was no difference between the genotypes in the odds of peripheral neuropathy when folate intake was ≤800 μg (OR: 1.5; 95% CI: 0.18, 12.33). The TCN2 776C→G polymorphism is associated with increased odds of peripheral neuropathy in the elderly, even with a normal vitamin B-12 status, especially if their folate intake is >2 times the Recommended Dietary Allowance. © 2016 American Society for Nutrition.

Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy-induced peripheral neuropathy in adolescents: A preliminary study.

PubMed

Tomasello, Caterina; Pinto, Rita Maria; Mennini, Chiara; Conicella, Elena; Stoppa, Francesca; Raucci, Umberto

2018-04-06

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy, in need of effective treatment. Preliminary data support the efficacy of scrambler therapy (ST), a noninvasive cutaneous electrostimulation device, in adults with CIPN. We test the efficacy, safety, and durability of ST for neuropathic pain in adolescents with CIPN. We studied nine pediatric patients with cancer and CIPN who received ST for pain control. Each patient received 45-min daily sessions for 10 consecutive days as a first step, but some of them required additional treatment. Pain significantly improved comparing Numeric Rate Scale after 10 days of ST (9.22 ± 0.83 vs. 2.33 ± 2.34; P < 0.001) and at the end of the optimized cycle (EOC) (9.22 ± 0.83 vs. 0.11 ± 0.33, P < 0.001). The improvement in quality of life was significantly reached on pain interference with general activity (8.67 ± 1.66 vs. 3.33 ± 2.12, P < 0.0001), mood (8.33 ± 3.32 vs. 2.78 ± 2.82, P < 0.0005), walking ability (10.00 vs. 2.78 ± 1.22, P < 0.0001), sleep (7.56 ± 2.24 vs. 2.67 ± 1.41, P < 0.001), and relations with people (7.89 ± 2.03 vs. 2.11 ± 2.03, P < 0.0002; Lansky score 26.7 ± 13.2 vs. 10 days of ST 57.8 ± 13.9, P < 0.001; 26.7 ± 13.2 vs. EOC 71.1 ± 16.2, P < 0.001). Based on these preliminary data, ST could be a good choice for adolescents with CIPN for whom pain control is difficult. ST caused total relief or dramatic reduction in CIPN pain and an improvement in quality of life, durable in follow-up. It caused no detected side effects, and can be retrained successfully. Further larger studies should be performed to confirm our promising preliminary data in pediatric patients with cancer. © 2018 Wiley Periodicals, Inc.

Genetics Home Reference: small fiber neuropathy

MedlinePlus

... Small fiber neuropathy is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which ... Page National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy Information Page Educational Resources (4 links) Johns Hopkins ...

Clinical and economic burdens experienced by patients with painful diabetic peripheral neuropathy: An observational study using a Japanese claims database.

PubMed

Ebata-Kogure, Nozomi; Nozawa, Kazutaka; Murakami, Aya; Toyoda, Tetsumi; Haga, Yuri; Fujii, Koichi

2017-01-01

Diabetic peripheral neuropathy (DPN) may often be painful. Despite the high prevalence of painful DPN (pDPN) among patients with diabetes mellitus (DM), understanding of its clinical and economic burden is limited. This study aimed to describe the clinical and economic burdens faced by patients with pDPN in Japan, and compared them with those experienced by patients with DPN but without painful symptoms (non-pDPN). This retrospective, observational study used data from a large-scale, hospital-based Japanese claims database collected from April 2008 to June 2015. Comorbidities, clinical departments visited, length of hospital stay, and medical costs for the period of ± 6 months from the diagnosis of pDPN or non-pDPN were described for each group. Glycemic control status was examined for each group for patients with glycated hemoglobin data. The data of 8,740 patients with pDPN (mean age 70.0 years, 53.4% male) and 12,592 patients with non-pDPN (mean age 67.7 years, 55.7% male) were analyzed. Patients with pDPN had more comorbidities than patients with non-pDPN; 48.7% and 30.9% of patients in the respective groups had 20 or more comorbidities. The median length of hospital stay was 5 days longer in patients with pDPN. The median total medical costs were higher in patients with pDPN (\\517,762) than in patients with non-pDPN (\\359,909). Patients with pDPN spent higher median costs for medications, but the costs for glycemic control drugs were similar in both groups. For 3,372 patients with glycated hemoglobin data, glycemic control was similar between the two groups. Patients with pDPN experienced greater clinical and economic burdens than patients with non-pDPN, suggesting that patients who develop pDPN may suffer not only from the complications of DM and pain, but also from other comorbid disorders.

Falls in persons with chemotherapy-induced peripheral neuropathy.

PubMed

Tofthagen, Cindy; Overcash, Janine; Kip, Kevin

2012-03-01

The purpose of this study was to evaluate possible risk factors for falls in a group of patients with chemotherapy-induced peripheral neuropathy (CIPN). This prospective, descriptive study included persons receiving paclitaxel, docetaxel, oxaliplatin, or cispatin who reported at least one symptom of CIPN. Each patient was invited to complete the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool (CIPNAT) and a demographic data questionnaire. Data were analyzed using descriptive statistics and logistic regression. In this sample (n = 109), fallers (n = 21) had higher doses of chemotherapy(p = 0.045), more neuropathic symptoms (p = 0.016), higher scores on the symptom experience (p = 0.005) and interference items (=0.001) on the CIPNAT, more severe muscle weakness (p < 0.001) and loss of balance (p < 0.001), and higher interference with walking(p < 0.001) and driving (p = 0.022). Patients who received taxanes were more likely to have fallen than patients who received platinum-based chemotherapy (p = 0.022). No significant differences in age or disease stage between fallers and non-fallers were present. Severity of loss of balance and cycle number was independently associated with falling. This study demonstrates that the risk of falls increases with each cycle of chemotherapy and that patients receiving taxanes may be at greater risk of falls than patients receiving neurotoxic platinum-based drugs. Patients who report muscle weakness and loss of balance or say that their symptoms interfere with walking or driving may be at a higher risk of falls.

Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lebo, R.V.; Li, L.Y.; Flandermeyer, R.R.

1994-09-01

Peripheral myelin protein (PMP-22) gene aneuploidy results in Charcot-Marie-Tooth disease Type 1A (CMT1A) and the Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) in Japanese patients as well as Caucasian Americans. Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, results when expression of one of at least seven genes is defective. CMT1A, about half of all CMT mutations, is usually associated with a duplication spanning the peripheral myelin protein-22 gene on distal chromosome band 17p11.2. Autosomal dominant HNPP (hereditary pressure and sensory neuropathy, HPSN) results from a deletion of the CMT1A gene region. Multicolor in situ hybridization with PMP-22 genemore » region probe characterized HNPP deletion reliably and detected all different size duplications reported previously. In summary, 72% of 28 Japanese CMT1 (HMSNI) patients tested had the CMT1A duplication, while none of the CMT2 (HMSNII) or CMT3 (HMSNIII) patients had a duplication. Three cases of HNPP were identified by deletion of the CMT1A gene region on chromosome 17p. HNPP and CMT1A have been reported to result simultaneously from the same unequal recombination event. The lower frequency of HNPP compared to CMT1A suggests that HNPP patients have a lower reproductive fitness than CMT1A patients. This result, along with a CMT1A duplication found in an Asian Indian family, demonstrates the broad geographic distribution and high frequency of PMP-22 gene aneuploidy.« less

Herbal Remedies: A Boon for Diabetic Neuropathy.

PubMed

Tiwari, Reshu; Siddiqui, Mohd Haris; Mahmood, Tarique; Bagga, Paramdeep; Ahsan, Farogh; Shamim, Arshiya

2018-03-26

Diabetic neuropathy is a chronic complication of diabetes mellitus affecting about 50% of patients. Its symptoms include decreased motility and severe pain in peripheral parts. The pathogenesis involved is an abnormality in blood vessels that supply the peripheral nerves, metabolic disorders such as myo-inositol depletion, and increased nonenzymatic glycation. Moreover, oxidative stress in neurons results in activation of multiple biochemical pathways, which results in the generation of free radicals. Apart from available marketed formulations, extensive research is being carried out on herbal-based natural products to control hyperglycemia and its associated complications. This review is focused to provide a summary on diabetic neuropathy covering its etiology, types, and existing work on herbal-based therapies, which include pure compounds isolated from plant materials, plant extracts, and Ayurvedic preparations.

Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor.

PubMed

Selvarajah, Dinesh; Gandhi, Rajiv; Emery, Celia J; Tesfaye, Solomon

2010-01-01

To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN). In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments. There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention. This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN.

Neurophysiological aspects of peripheral neuropathies.

PubMed

MacKenzie, R A; Skuse, N F; Lethlean, A K

1976-01-01

1. Eighty-eight intrafascicular neural recordings were obtained in 10 normal subjects, 5 patients with axonal degeneration and 11 patients with demyelinating neuropathy. 2. Stimulus levels required for perception and fibre activation were higher in neuropathic subjects. Fibres transmitting touch perception had significantly lower conduction velocities in both patient groups, but were very much lower in the group with demyelinating neuropahty than the group with axonal degeneration. Maximum electrical stimulation evoked dispersed fibre responses in the axonal degeneration group and more dispersed, slowly conducting fibre potentials in the demyelinating group. In patients with hypertrophic Charcot-Marie-Tooth disorder, usually only a small group of slowly conducting low amplitude potentials was recorded. 3. Delivery of a train of supramaximal stimuli caused prolongation of latency and dispersion of fibre potentials in all microneurographic recordings. The changes were significantly greater in the axonal neuropathy group than in normals, and recovery was slower. The demyelinating neuropathies showed significantly greater changes than both the normal and the axonal neuropathy groups, and post-tetanic conduction slowing became even more marked after limb temperature was raised. 4. Surface SAP recordings showed normal refractory period in chronic axonal neuropathy but significant latency prolongation occurred in demyelinating neuropathy. 5. It is concluded that both receptor and nerve fibre abnormalities contribute to sensory dysfunction in degenerative and demyelinating neuropathies.

[Artificial control of blood-nerve barrier: a novel therapeutic approach to peripheral neuropathies].

PubMed

Kanda, Takashi

2011-11-01

Blood-nerve barrier (BNB) is a "Janus-faced" structure for the peripheral nerve parenchyma. Healthy BNB may contribute to stabilize the internal milleu of peripheral nervous system (PNS) and to stop the entrance of toxic substances and harmful leukocytes into nerve parenchyma. On the other hand, healthy BNB may sometimes be a drawback because the peripheral nerve parenchyma cannot receive enough amount of nutrients and growth factors and cannot excrete toxic substances into systemic circulation because of its presence. Here we present a future therapeutic strategy to control BNB function, based on the basic knowledge acquired from recently developed human immortalized cell lines of BNB origin. If we can artificially regulate the BNB permeability and the expression of adhesion molecules on the surface of BNB-forming endothelial cells, and stop the entrance of toxic substances as well as pathogenic leukocytes into PNS parenchyma, the treatment of inflammatory neuropathies may make great progresses. For hereditary, metabolic and ischemic neuropathies, the promotion of the entrance of growth factors into PNS parenchyma and of the excretion of toxic substances should powerfully encourage the regeneration of axons.

Integrating data from randomized controlled trials and observational studies to predict the response to pregabalin in patients with painful diabetic peripheral neuropathy.

PubMed

Alexander, Joe; Edwards, Roger A; Savoldelli, Alberto; Manca, Luigi; Grugni, Roberto; Emir, Birol; Whalen, Ed; Watt, Stephen; Brodsky, Marina; Parsons, Bruce

2017-07-20

More patient-specific medical care is expected as more is learned about variations in patient responses to medical treatments. Analytical tools enable insights by linking treatment responses from different types of studies, such as randomized controlled trials (RCTs) and observational studies. Given the importance of evidence from both types of studies, our goal was to integrate these types of data into a single predictive platform to help predict response to pregabalin in individual patients with painful diabetic peripheral neuropathy (pDPN). We utilized three pivotal RCTs of pregabalin (398 North American patients) and the largest observational study of pregabalin (3159 German patients). We implemented a hierarchical cluster analysis to identify patient clusters in the Observational Study to which RCT patients could be matched using the coarsened exact matching (CEM) technique, thereby creating a matched dataset. We then developed autoregressive moving average models (ARMAXs) to estimate weekly pain scores for pregabalin-treated patients in each cluster in the matched dataset using the maximum likelihood method. Finally, we validated ARMAX models using Observational Study patients who had not matched with RCT patients, using t tests between observed and predicted pain scores. Cluster analysis yielded six clusters (287-777 patients each) with the following clustering variables: gender, age, pDPN duration, body mass index, depression history, pregabalin monotherapy, prior gabapentin use, baseline pain score, and baseline sleep interference. CEM yielded 1528 unique patients in the matched dataset. The reduction in global imbalance scores for the clusters after adding the RCT patients (ranging from 6 to 63% depending on the cluster) demonstrated that the process reduced the bias of covariates in five of the six clusters. ARMAX models of pain score performed well (R 2 : 0.85-0.91; root mean square errors: 0.53-0.57). t tests did not show differences between observed

The Influence of Nicotine on Lung Tumor Growth, Cancer Chemotherapy, and Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Kyte, S Lauren; Gewirtz, David A

2018-06-04

Studies in animal models have suggested that nicotine, an agonist of nicotinic acetylcholine receptors (nAChRs), may have the potential to prevent and/or reverse the peripheral neuropathy induced by cancer chemotherapeutic drugs, such as paclitaxel and oxaliplatin. However, a large body of evidence suggests that nicotine may also stimulate lung tumor growth and/or interfere with the effectiveness of cancer chemotherapy. While the reported proliferative effects of nicotine are highly variable, the antagonism of antitumor drug efficacy is more consistent, although this latter effect has been demonstrated primarily in cell culture studies. In contrast, in vitro and in vivo studies from our own laboratory indicate that nicotine fails to enhance the growth of non-small cell lung cancer cells or attenuate the effects of chemotherapy (paclitaxel). Given the inconsistencies in the literature, coupled with our own findings, the weight of evidence suggests that caution may be warranted in proposing to utilize nicotine to mitigate chemotherapy-induced peripheral neuropathy in cancer patients receiving chemotherapy. Conversely, clinical trials could be performed in patients who have completed therapy and are considered to be disease-free to determine whether nicotine, in the form of commercially available patches or gum, is effective in alleviating peripheral neuropathy symptoms. The American Society for Pharmacology and Experimental Therapeutics.

[Metronidazole-induced reversible cerebellar lesions and peripheral neuropathy].

PubMed

Toumi, S; Hammouda, M; Essid, A; Medimagh, L; Slamia, L Ben; Laouani-Kechrid, C

2009-12-01

Metronidazole is a widely prescribed treatment for amoebic and anaerobic germ infections. Its neurologic toxicity is rare but can be serious. We report the case of a 27-year-old male patient, treated with metronidazole for a cerebral abscess. He presented with a cerebellar syndrome and peripheral neuropathy at a cumulative metronidazole dose of 60g. The MRI aspect of the cerebellar lesions in addition to their reversibility after treatment cessation led to the diagnosis of metronidazole induced neurologic toxicity. The occurrence of neurologic disorders in patients treated with metronidazole must suggest drug toxicity and lead to cessation of treatment.

Cross sectional study to evaluate the effect of duration of type 2 diabetes mellitus on the nerve conduction velocity in diabetic peripheral neuropathy.

PubMed

Hussain, Gauhar; Rizvi, S Aijaz Abbas; Singhal, Sangeeta; Zubair, Mohammad; Ahmad, Jamal

2014-01-01

To study the nerve conduction velocity in clinically undetectable and detectable peripheral neuropathy in type 2 diabetes mellitus with variable duration. This cross sectional study was conducted in diagnosed type 2 diabetes mellitus patients. They were divided in groups: Group I (n=37) with clinically detectable diabetic peripheral neuropathy of shorter duration and Group II (n=27) with clinically detectable diabetic peripheral neuropathy of longer duration. They were compared with T2DM patients (n=22) without clinical neuropathy. Clinical diagnosis was based on neuropathy symptom score (NSS) and neuropathy disability score (NDS) for signs. Nerve conduction velocity was measured in both upper and lower limbs. Median, ulnar, common peroneal and posterior tibial nerves were selected for motor nerve conduction study and median and sural nerves were selected for sensory nerve conduction study. The comparisons were done between nerve conduction velocities of motor and sensory nerves in patients of clinically detectable neuropathy and patients without neuropathy in type 2 diabetes mellitus population. This study showed significant electrophysiological changes with duration of disease. Nerve conduction velocities in lower limbs were significantly reduced even in patients of shorter duration with normal upper limb nerve conduction velocities. Diabetic neuropathy symptom score (NSS) and neuropathy disability score (NDS) can help in evaluation of diabetic sensorimotor polyneuropathy though nerve conduction study is more powerful test and can help in diagnosing cases of neuropathy. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Insulin-induced upregulation of lipoprotein lipase in Schwann cells during diabetic peripheral neuropathy.

PubMed

Rachana, Kuruvanthe S; Manu, Mallahalli S; Advirao, Gopal M

2018-03-17

Diabetic peripheral neuropathy (DPN) is one of the major complications associated with diabetes. It is characterized by the degeneration of the myelin sheath around axons, referred to as demyelination. Such demyelinations are often caused by reduced lipid component of the myelin sheath. Since, lipoprotein lipase (LPL) provides the lipid for myelin sheath by hydrolysing the triglyceride rich lipoproteins, and also helps in the uptake of lipids by the Schwann cells (SCs) for its utilization, LPL is considered as the important factor in the regeneration of myelin sheath during diabetic neuropathy. Earlier reports from our laboratory have provided the insights of insulin and its receptor in SCs during diabetic neuropathy. In order to evaluate the long term effect of insulin on lipid metabolism during diabetic neuropathy, in this study, we analyzed the expression of LPL in SCs under normal, high glucose and insulin treated conditions. A decrease in the expression of LPL was observed in SCs of high glucose condition and it was reversed upon insulin treatment. Histochemical observations of sciatic nerve of insulin treated neuropathy subjects showed the improved nerve morphology, signifying the importance of insulin in restoring the pathophysiology of diabetic neuropathy. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Walking stability and sensorimotor function in older people with diabetic peripheral neuropathy.

PubMed

Menz, Hylton B; Lord, Stephen R; St George, Rebecca; Fitzpatrick, Richard C

2004-02-01

To evaluate, in older people with diabetic peripheral neuropathy (DPN) and in age-matched controls, acceleration patterns of the head and pelvis when walking to determine the effect of lower-limb sensory loss on walking stability. Case-control study. Falls and balance laboratory in Australia. Thirty persons with diabetes mellitus (age range, 55-91 y) and 30 age-matched controls. Acceleration patterns of the head and pelvis were measured while participants walked on a level surface and an irregular walkway. Participants also underwent tests of vision, sensation, strength, reaction time, and balance. Temporospatial gait parameters and variables derived from acceleration signals. Participants with DPN had reduced walking speed, cadence, and step length, and less rhythmic acceleration patterns at the head and pelvis compared with controls. These differences were particularly evident when participants walked on the irregular surface. Participants with DPN also had impaired peripheral sensation, reaction time, and balance. Older people with DPN have an impaired ability to stabilize their body when walking on irregular surfaces, even if they adopt a more conservative gait pattern. These results provide further insights into the role of peripheral sensory input in the control of gait stability, and suggest possible mechanisms underlying the increased risk of falling in older people with diabetic neuropathy.

A quantitative sensory analysis of peripheral neuropathy in colorectal cancer and its exacerbation by oxaliplatin chemotherapy.

PubMed

de Carvalho Barbosa, Mariana; Kosturakis, Alyssa K; Eng, Cathy; Wendelschafer-Crabb, Gwen; Kennedy, William R; Simone, Donald A; Wang, Xin S; Cleeland, Charles S; Dougherty, Patrick M

2014-11-01

Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aβ myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy. ©2014 American Association for Cancer Research.

Effects of sweet bee venom pharmacopuncture treatment for chemotherapy-induced peripheral neuropathy: a case series.

PubMed

Park, Jae-Woo; Jeon, Ju-Hyun; Yoon, Jeungwon; Jung, Tae-Young; Kwon, Ki-Rok; Cho, Chong-Kwan; Lee, Yeon-Weol; Sagar, Stephen; Wong, Raimond; Yoo, Hwa-Seung

2012-06-01

This is a case series reporting safety and degree of response to 1 dose level of sweet bee venom pharmacopuncture (SBVP) or melittin as a symptom-control therapy for chemotherapy-induced peripheral neuropathy (CIPN). All treatments were conducted at the East West Cancer Center (EWCC), Dunsan Oriental Hospital, Daejeon University, Republic of Korea, an institution that uses complementary therapies for cancer patients. Five consecutive patients with CIPN were referred to the EWCC from March 20, 2010, to April 10, 2010. Patients with World Health Organization Chemotherapy-Induced Peripheral Neuropathy (WHO CIPN) grade 2 or more were treated with SBVP for 3 treatment sessions over a 1-week period. Measures of efficacy and safety. Validated Visual Analog System (VAS) pain scale, WHO CIPN grade, and Functional Assessment of Cancer Therapy-General (FACT-G) were compared before and after the 1-week course of treatment. To ensure the safety of SBVP, pretreatment skin response tests were given to patients to avoid any potential anaphylactic adverse effects. All patients were closely examined for any allergenic responses following each treatment session. One patient discontinued treatment after the first session, and 4 patients completed all treatment sessions. Using each patient as their own comparator, marked improvements of VAS, WHO CIPN grade, and physical section scores of FACT-G were seen in 3 patients. Most important, there were no related adverse side effects found. This safety results of the SBVP therapy merits further investigations in a larger size trial for it to develop into a potential intervention for managing CIPN symptoms. This study will be extended to a dose-response evaluation to further establish safety and response, prior to a randomized trial.

Gasoline sniffing multifocal neuropathy.

PubMed

Burns, T M; Shneker, B F; Juel, V C

2001-11-01

The polyneuropathy caused by chronic gasoline inhalation is reported to be a gradually progressive, symmetric, sensorimotor polyneuropathy. We report unleaded gasoline sniffing by a female 14 years of age that precipitated peripheral neuropathy. In contrast with the previously reported presentation of peripheral neuropathy in gasoline inhalation, our patient developed multiple mononeuropathies superimposed on a background of sensorimotor polyneuropathy. The patient illustrates that gasoline sniffing neuropathy may present with acute multiple mononeuropathies resembling mononeuritis multiplex, possibly related to increased peripheral nerve susceptibility to pressure in the setting of neurotoxic components of gasoline. The presence of tetraethyl lead, which is no longer present in modern gasoline mixtures, is apparently not a necessary factor in the development of gasoline sniffer's neuropathy.

Use of a Novel High-Resolution Magnetic Resonance Neurography Protocol to Detect Abnormal Dorsal Root Ganglia in Sjögren Patients With Neuropathic Pain

PubMed Central

Birnbaum, Julius; Duncan, Trisha; Owoyemi, Kristie; Wang, Kenneth C.; Carrino, John; Chhabra, Avneesh

2014-01-01

Abstract The diagnosis and treatment of patients with Sjögren syndrome (SS) with neuropathic pain pose several challenges. Patients with SS may experience unorthodox patterns of burning pain not conforming to a traditional “stocking-and-glove” distribution, which can affect the face, torso, and proximal extremities. This distribution of neuropathic pain may reflect mechanisms targeting the proximal-most element of the peripheral nervous system—the dorsal root ganglia (DRG). Skin biopsy can diagnose such a small-fiber neuropathy and is a surrogate marker of DRG neuronal cell loss. However, SS patients have been reported who have similar patterns of proximal neuropathic pain, despite having normal skin biopsy studies. In such cases, DRGs may be targeted by mechanisms not associated with neuronal cell loss. Therefore, alternative approaches are warranted to help characterize abnormal DRGs in SS patients with proximal neuropathic pain. We performed a systematic review of the literature to define the frequency and spectrum of SS peripheral neuropathies, and to better understand the attribution of SS neuropathic pain to peripheral neuropathies. We found that the frequency of SS neuropathic pain exceeded the prevalence of peripheral neuropathies, and that painful peripheral neuropathies occurred less frequently than neuropathies not always associated with pain. We developed a novel magnetic resonance neurography (MRN) protocol to evaluate DRG abnormalities. Ten SS patients with proximal neuropathic pain were evaluated by this MRN protocol, as well as by punch skin biopsies evaluating for intraepidermal nerve fiber density (IENFD) of unmyelinated nerves. Five patients had radiographic evidence of DRG abnormalities. Patients with MRN DRG abnormalities had increased IENFD of unmyelinated nerves compared to patients without MRN DRG abnormalities (30.2 [interquartile range, 4.4] fibers/mm vs. 11.0 [4.1] fibers/mm, respectively; p = 0.03). Two of these 5 SS patients

Plantar pressure in diabetic peripheral neuropathy patients with active foot ulceration, previous ulceration and no history of ulceration: a meta-analysis of observational studies.

PubMed

Fernando, Malindu Eranga; Crowther, Robert George; Pappas, Elise; Lazzarini, Peter Anthony; Cunningham, Margaret; Sangla, Kunwarjit Singh; Buttner, Petra; Golledge, Jonathan

2014-01-01

Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP) and pressure time integral (PTI) were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310). Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290-0.811, p<0.001; and 0.762, 95% CI 0.303-1.221, p = 0.001, respectively). Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181- 0.753, p = 0.001). Statistical heterogeneity between studies was moderate. Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More

Clinical Phenotype of Diabetic Peripheral Neuropathy and Relation to Symptom Patterns: Cluster and Factor Analysis in Patients with Type 2 Diabetes in Korea.

PubMed

Won, Jong Chul; Im, Yong-Jin; Lee, Ji-Hyun; Kim, Chong Hwa; Kwon, Hyuk Sang; Cha, Bong-Yun; Park, Tae Sun

2017-01-01

Patients with diabetic peripheral neuropathy (DPN) is the most common complication. However, patients are usually suffering from not only diverse sensory deficit but also neuropathy-related discomforts. The aim of this study is to identify distinct groups of patients with DPN with respect to its clinical impacts on symptom patterns and comorbidities. A hierarchical cluster analysis and factor analysis were performed to identify relevant subgroups of patients with DPN ( n = 1338) and symptom patterns. Patients with DPN were divided into three clusters: asymptomatic (cluster 1, n = 448, 33.5%), moderate symptoms with disturbed sleep (cluster 2, n = 562, 42.0%), and severe symptoms with decreased quality of life (cluster 3, n = 328, 24.5%). Patients in cluster 3, compared with clusters 1 and 2, were characterized by higher levels of HbA1c and more severe pain and physical impairments. Patients in cluster 2 had moderate pain levels but disturbed sleep patterns comparable to those in cluster 3. The frequency of symptoms on each item of MNSI by "painful" symptom pattern showed a similar distribution pattern with increasing intensities along the three clusters. Cluster and factor analysis endorsed the use of comprehensive and symptomatic subgrouping to individualize the evaluation of patients with DPN.

The effects of Vibro-medical insole on vibrotactile sensation in diabetic patients with mild-to-moderate peripheral neuropathy.

PubMed

Bagherzadeh Cham, Masumeh; Mohseni-Bandpei, Mohammad Ali; Bahramizadeh, Mahmood; Kalbasi, Saeed; Biglarian, Akbar

2018-06-01

Peripheral sensory neuropathy seems to be the main risk factor for diabetic foot ulceration. Previous studies demonstrated that stochastic resonance can improve the vibrotactile sensation of diabetic patients. The aim of this study was to evaluate the effects of Vibro-medical insole on pressure and vibration sensation in diabetic patients with mild-to-moderate peripheral neuropathy. A total of 20 patients with mild-to-moderate diabetic neuropathy were included in the pre-test and post-test clinical trial study. Vibro-medical insole consists of medical insole and vibratory system. Medical insole was made independently for each participant and vibratory system was inserted in it. Pressure and vibration sensation were evaluated before and after 30-min walking with Vibro-medical insole. Semmes-Weinstein monofilaments and tuning fork were used to evaluate pressure and vibration sensation, respectively. Pressure sensation showed significantly improvement using Vibro-medical insole at the heel, first and fifth metatarsophalangeal heads, and hallux of both feet in all participants (p < 0.001). Vibration sensation also improved at the big toe of both feet with 256 Hz tuning fork (p < 0.05) but no statistically significant effect was found with 128 Hz tuning fork (p > 0.05). Vibro-medical insole significantly improved pressure and vibration sensation of the foot in diabetic patients with mild-to-moderate peripheral neuropathy. The results suggest that Vibro-medical insole can be used for daily living activities to overcome sensory loss in diabetic neuropathy patients.

Cramp-fasciculation syndrome associated with monofocal motor neuropathy.

PubMed

Dubuisson, Nicolas J; Van Pesch, Vincent; Van Den Bergh, Peter Y K

2017-10-01

Cramp-fasciculation syndrome is a peripheral nerve hyperexcitability disorder, which could be caused by inflammatory neuropathy. We describe a 51-year-old woman who presented with a 4- to 5-year history of fasciculations and painful cramping of the right thenar eminence. Electrophysiological studies showed motor conduction block in the right median nerve between the axilla and the elbow with fasciculation potentials and cramp discharges on electromyography in the right abductor pollicis brevis muscle. High titers of serum anti-GM1 immunoglobulin M antibodies were detected. Monofocal motor neuropathy of the right median nerve was diagnosed. Intravenous immunoglobulin treatment led to significant improvement of symptoms and signs. Although fasciculations and cramps have been reported in multifocal motor neuropathy and are considered supporting criteria for the diagnosis, the occurrence of cramp-fasciculation syndrome as the presenting feature and predominant manifestation in monofocal motor neuropathy, a variant of multifocal motor neuropathy, is unique. Muscle Nerve 56: 828-832, 2017. © 2017 Wiley Periodicals, Inc.