Lelia Gonçalves Rocha Martin
Full Text Available Peripheral neuropathy is a common side effect in patients undergoing cancer treatment with chemotherapy. This condition can affect patients in several different ways, interfering in their activities of daily living and autonomy. The present study aimed to review the literature on chemotherapy-induced peripheral neuropathy and its treatment or other possible interventions. The findings reveal that chemotherapy-induced peripheral neuropathy is a common condition that affects patients undergoing treatment with some specific drugs. Besides, several different substances have been used to treat or control this condition, although no significant evidence could be found in these studies.
It usually starts in the hands and/or feet and creeps up the arms and legs. Sometimes it feels like a tingling or numbness. Other times, it’s more of a shooting and/or burning pain or sensitivity to temperature. It can include sharp, stabbing pain, and it can make it difficult to perform normal day-to-day tasks like buttoning a shirt, sorting coins in a purse, or walking. An estimated 30 to 40 percent of cancer patients treated with chemotherapy experience these symptoms, a condition called chemotherapy-induced peripheral neuropathy (CIPN). |
Pachman, Deirdre R; Watson, James C; Lustberg, Maryam B; Wagner-Johnston, Nina D; Chan, Alexandre; Broadfield, Larry; Cheung, Yin Ting; Steer, Christopher; Storey, Dawn J; Chandwani, Kavita D; Paice, Judith; Jean-Pierre, Pascal; Oh, Jeong; Kamath, Jayesh; Fallon, Marie; Strik, Herwig; Koeppen, Susanne; Loprinzi, Charles L
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a variety of chemotherapeutic agents. Clinicians are cognizant of the negative impact of CIPN on cancer treatment outcomes and patients' psychosocial functioning and quality of life. In an attempt to alleviate this problem, clinicians and patients try various therapeutic interventions, despite limited evidence to support efficacy of these treatments. The rationale for such use is mostly based on the evidence for the treatment options in non-CIPN peripheral neuropathy syndromes, as this area is more robustly studied than is CIPN treatment. In this manuscript, we examine the existing evidence for both CIPN and non-CIPN treatments and develop a summary of the best available evidence with the aim of developing a practical approach to the treatment of CIPN, based on available literature and clinical practice experience.
Krukowski, Karen; Ma, Jiacheng; Golonzhka, Olga; Laumet, Geoffroy O; Gutti, Tanuja; van Duzer, John H; Mazitschek, Ralph; Jarpe, Matthew B; Heijnen, Cobi J; Kavelaars, Annemieke
Chemotherapy-induced peripheral neuropathy is one of the most common dose-limiting side effects of cancer treatment. Currently, there is no Food and Drug Administration-approved treatment available. Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase whose function includes regulation of α-tubulin-dependent intracellular mitochondrial transport. Here, we examined the effect of HDAC6 inhibition on established cisplatin-induced peripheral neuropathy. We used a novel HDAC6 inhibitor ACY-1083, which shows 260-fold selectivity towards HDAC6 vs other HDACs. Our results show that HDAC6 inhibition prevented cisplatin-induced mechanical allodynia, and also completely reversed already existing cisplatin-induced mechanical allodynia, spontaneous pain, and numbness. These findings were confirmed using the established HDAC6 inhibitor ACY-1215 (Ricolinostat), which is currently in clinical trials for cancer treatment. Mechanistically, treatment with the HDAC6 inhibitor increased α-tubulin acetylation in the peripheral nerve. In addition, HDAC6 inhibition restored the cisplatin-induced reduction in mitochondrial bioenergetics and mitochondrial content in the tibial nerve, indicating increased mitochondrial transport. At a later time point, dorsal root ganglion mitochondrial bioenergetics also improved. HDAC6 inhibition restored the loss of intraepidermal nerve fiber density in cisplatin-treated mice. Our results demonstrate that pharmacological inhibition of HDAC6 completely reverses all the hallmarks of established cisplatin-induced peripheral neuropathy by normalization of mitochondrial function in dorsal root ganglia and nerve, and restoration of intraepidermal innervation. These results are especially promising because one of the HDAC6 inhibitors tested here is currently in clinical trials as an add-on cancer therapy, highlighting the potential for a fast clinical translation of our findings.
Gewandter, Jennifer S; Freeman, Roy; Kitt, Rachel A; Cavaletti, Guido; Gauthier, Lynn R; McDermott, Michael P; Mohile, Nimish A; Mohlie, Supriya G; Smith, A Gordon; Tejani, Mohamedtaki A; Turk, Dennis C; Dworkin, Robert H
To assess the design characteristics and reporting quality of published randomized controlled trials (RCTs) for treatments of chemotherapy-induced peripheral neuropathy (CIPN) initiated before or during chemotherapy. In this systematic review of RCTs of preventive or symptomatic pharmacologic treatments for CIPN initiated before or during chemotherapy treatment, articles were identified by updating the PubMed search utilized in the CIPN treatment guidelines published in the Journal of Clinical Oncology in 2014. Thirty-eight articles were identified. The majority included only patients receiving platinum therapies (61%) and used a placebo control (79%). Common exclusion criteria were preexisting neuropathy (84%), diabetes (55%), and receiving treatments that could potentially improve neuropathy symptoms (45%). Ninety-five percent of studies initiated the experimental treatment before CIPN symptoms occurred. Although 58% of articles identified a primary outcome measure (POM), only 32% specified a primary analysis. Approximately half (54%) of the POMs were patient-reported outcome measures of symptoms and functional impairment. Other POMs included composite measures of symptoms and clinician-rated signs (23%) and vibration tests (14%). Only 32% of articles indicated how data from participants who prematurely discontinued chemotherapy were analyzed, and 21% and 29% reported the number of participants who discontinued chemotherapy due to neuropathy or other/unspecified reasons, respectively. These data identify reporting practices that could be improved in order to enhance readers' ability to critically evaluate RCTs of CIPN treatments and use the findings to inform the design of future studies and clinical practice. Reporting recommendations are provided. © 2017 American Academy of Neurology.
Full Text Available Chemotherapy induced peripheral neuropathy (CIPN is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a ‘stocking and glove’ distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of CIPN. New insights on the pathobiology of CIPN gained using these models are discussed in this review. These include mitochondrial dysfunction and oxidative stress that are implicated as key mechanisms in the development of CIPN. Associated structural changes in peripheral nerves include neuronopathy, axonopathy and/or myelinopathy, especially intra-epidermal nerve fiber (IENF degeneration. In patients with CIPN, loss of heat sensitivity is a hallmark symptom due to preferential damage to myelinated primary afferent sensory nerve fibers in the presence or absence of demyelination. The pathobiology of CIPN is complex as cancer chemotherapy treatment regimens frequently involve drug combinations. Adding to this complexity, there are also subtle differences in the pathobiological consequences of commonly used cancer chemotherapy drugs, viz platinum compounds, taxanes, vincristine, bortezomib, thalidomide and ixabepilone, on peripheral nerves.
Kawata, Daisuke; Wu, Zetang
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 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.
Kawata, Daisuke; Wu, Zetang
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.
Elaine G Boland
Full Text Available Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN with those from healthy volunteers (HV. Twenty-four participants (n = 12 MM-CIPN, n = 12 HV underwent Blood Oxygen Level-Dependent (BOLD fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected. Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected. Significant positive correlation existed between the total neuropathy score (reduced version and activation in the frontal operculum (close to insular cortex during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87. Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.
Karen Y. Wonders
Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is a common, dose-limiting effect of cancer therapy that often has negative implications on a patient’s quality of life. The pain associated with CIPN has long been recognized as one of the most difficult types of pain to treat. Historically, much effort has been made to explore pharmacological therapies aimed at reducing symptoms of CIPN. While many of these agents provide a modest relief in the symptoms of peripheral neuropathy, many have been shown to have additional negative side effects for cancer patients. Therefore, the authors suggest exercise rehabilitation as one lifestyle modification that may positively impact the lives of patients with CIPN. To our knowledge, there are currently no published clinical trials examining the role of exercise in preserving neurological function following chemotherapy. However, investigations using low-to-moderate intensity exercise as an intervention in patients with diabetic peripheral neuropathy and hereditary motor and sensory neuropathies have produced promising results. Given that cancer patients appear to tolerate exercise, it seems plausible that exercise rehabilitation could be used as an effective strategy to minimize CIPN-induced detriments to quality of life.
Gilchrist, L S; Marais, L; Tanner, L
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment in children; however, measurement of CIPN has been hampered by limitations in available tools, which may impact prevalence estimates. The purpose of this study was to assess the relative ability of the Common Terminology Criteria (CTCAE) rating process to detect sensory and motor neuropathy as compared to administration of the pediatric modified Total Neuropathy Score (peds-mTNS). The ped-mTNS was administered to 60 children/adolescents ages 5-18 undergoing treatment for acute lymphocytic leukemia, lymphoma, or non-CNS solid tumors. CTCAE v3.0 scores for the same time point were abstracted from the medical record by a separate trained rater. Comparisons were made between scores using descriptive statistics, correlations, and specificity and sensitivity calculations. The median ped-mTNS score was 9 (32 possible), while the median sensory and motor CTCAE ratings were 0 and 2, respectively (4 and 5 possible, respectively). There was no correlation between ped-mTNS and combined sensory and motor CTCAE scores. The only ped-mTNS item with significant correlation to CTCAE scoring was strength testing. Medical record abstraction of CTCAE scores failed to identify sensory neuropathy in 40 % and significant motor neuropathy (manual muscle test grade 3 or worse) in 15 % of subjects. Prospective measures of CIPN using the ped-mTNS identified a far greater proportion of subjects with peripheral neurotoxicity as compared to CTCAE v3.0 sensory and motor neuropathy ratings, and thus we recommend the use of a specific measure of CIPN such as the ped-mTNS.
Derksen, T.; Bours, M.J.; Mols, F.; Weijenberg, M.P.
Background. Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of chemotherapy treatment in colorectal cancer (CRC), negatively affecting the daily functioning and quality of life of CRC patients. Currently, there are no established treatments to prevent or reduce CIPN. The
Heuvel, S.A.S. van den; Wal, S.E.I. van der; Smedes, L.A.; Radema, S.A.; Alfen, N. van; Vissers, K.C.P.; Steegers, M.A.H.
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
Full Text Available 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.
Cunningham, Joan Elizabeth; Kelechi, Teresa; Sterba, Katherine; Barthelemy, Nikki; Falkowski, Paul; Chin, Steve H
Chemotherapy-induced peripheral neuropathy (CIPN) is a common, miserable, potentially severe, and often dose-limiting side effect of several first and second-line anti-cancer agents with little in the way of effective, acceptable treatment. Although mechanisms of damage differ, manual therapy (therapeutic massage) has effectively reduced symptoms and improved quality of life in patients with diabetic peripheral neuropathy. Here, we describe application of manual therapy (techniques of effleurage and petrissage) to the extremities in a patient with grade 2 CIPN subsequent to prior treatment with docetaxel and cisplatin for stage III esophageal adenocarcinoma. Superficial cutaneous temperature was monitored using infrared thermistry as proxy for microvascular blood flow. By the end of the course of manual therapy without any change in medications, CIPN symptoms were greatly reduced to grade 1, with corresponding improvement in quality of life. Improvements in superficial temperature were observed in fingers and toes. Manual therapy was associated with almost complete resolution of the tingling and numbness and pain of CIPN in this patient. Concurrently increased superficial temperature suggests improvements in CIPN symptoms may have involved changes in blood circulation. To our knowledge, this is the first report of using manual therapy for amelioration of CIPN.
Full Text Available Objective: Neurological complications such as chemotherapy-induced peripheral neuropathy (CIPN and neuropathic pain are frequent side effects of neurotoxic chemotherapy agents. An increasing survival rate and frequent administration of adjuvant chemotherapy treatments involving neurotoxic agents makes it imperative that accurate diagnosis, prevention, and treatment of these neurological complications be implemented. Methods: A consideration was undertaken of the current options regarding protective and treatment interventions for patients undergoing chemotherapy with neurotoxic chemotherapy agent or experience with CIPN. Current knowledge on the mechanism of action has also been identified. The following databases PubMed, the Cochrane Library, Science Direct, Scopus, EMBASE, MEDLINE, CINAHL, CNKI, and Google Scholar were searched for relevant article retrieval. Results: A range of pharmaceutical, nutraceutical, and herbal medicine treatments were identified that either showed efficacy or had some evidence of efficacy. Duloxetine was the most effective pharmaceutical agent for the treatment of CIPN. Vitamin E demonstrated potential for the prevention of cisplatin-IPN. Intravenous glutathione for oxaliplatin, Vitamin B6 for both oxaliplatin and cisplatin, and omega 3 fatty acids for paclitaxel have shown protection for CIPN. Acetyl-L-carnitine may provide some relief as a treatment option. Acupuncture may be of benefit for some patients and Gosha-jinki-gan may be of benefit for protection from adverse effects of oxaliplatin induced peripheral neuropathy. Conclusions: Clinicians and researchers acknowledge that there are numerous challenges involved in understanding, preventing, and treating peripheral neuropathy caused by chemotherapeutic agents. New insights into mechanisms of action from chemotherapy agents may facilitate the development of novel preventative and treatment options, thereby enabling medical staff to better support patients by
Prinsloo, Sarah; Novy, Diane; Driver, Larry; Lyle, Randall; Ramondetta, Lois; Eng, Cathy; McQuade, Jennifer; Lopez, Gabriel; Cohen, Lorenzo
Chemotherapy-induced peripheral neuropathy (CIPN) is a significant problem for cancer patients, and there are limited treatment options for this often debilitating condition. Neuromodulatory interventions could be a novel modality for patients trying to manage CIPN symptoms; however, they are not yet the standard of care. This study examined whether electroencephalogram (EEG) neurofeedback (NFB) could alleviate CIPN symptoms in survivors. This was a randomized controlled trial with survivors assigned to an NFB group or a wait-list control (WLC) group. The NFB group underwent 20 sessions of NFB, in which visual and auditory rewards were given for voluntary changes in EEGs. The Brief Pain Inventory (BPI) worst-pain item was the primary outcome. The BPI, the Pain Quality Assessment Scale, and EEGs were collected before NFB and again after treatment. Outcomes were assessed with general linear modeling. Cancer survivors with CIPN (average duration of symptoms, 25.3 mo), who were mostly female and had a mean age of 62.5 years, were recruited between April 2011 and September 2014. One hundred percent of the participants starting the NFB program completed it (30 in the NFB group and 32 in the WLC group). The NFB group demonstrated greater improvement than the controls on the BPI worst-pain item (mean change score, -2.43 [95% confidence interval, -3.58 to -1.28] vs 0.09 [95% confidence interval, -0.72 to -0.90]; P =·.001; effect size, 0.83). NFB appears to be effective at reducing CIPN symptoms. There was evidence of neurological changes in the cortical location and in the bandwidth targeted by the intervention, and changes in EEG activity were predictive of symptom reduction. Cancer 2017;123:1989-1997. © 2017 American Cancer Society. © 2017 American Cancer Society.
Cox-Martin, Emily; Trahan, Lisa H; Cox, Matthew G; Dougherty, Patrick M; Lai, Emily A; Novy, Diane M
Chemotherapy-induced peripheral neuropathy (CIPN) and obesity are prevalent in cancer survivors and decrease quality of life; however, the impact of the co-occurrence of these conditions has garnered little attention. This study investigated differences between obese and non-obese cancer survivors with CIPN and predictors of symptom burden and pain. Patients with CIPN were administered the MD Anderson Symptom Inventory and a modified version of pain descriptors from the McGill Pain Inventory. Independent t tests assessed group differences between obese and non-obese survivors, and linear regression analyses explored predictors of patient outcomes. Results indicated a significant difference in symptom severity scores for obese (M = 32.89, SD = 25.53) versus non-obese (M = 19.35, SD = 16.08) patients (t(37.86) = -2.49, p = .02). Significant differences were also found for a total number of pain descriptors endorsed by obese (M = 4.21, SD = 3.45) versus non-obese (M = 2.42, SD = 2.69) participants (t(74) = -2.53, p = .01). Obesity was a significant predictor of symptom severity and total pain descriptors endorsed. Other significant predictors included age and months since treatment. Cancer survivors with CIPN and co-occurring obesity may be more at risk for decreased quality of life through increased symptom severity and pain compared to non-obese survivors. This paper identified risk factors, including obesity, age, and months since treatment, that can be clinically identified for monitoring distress in CIPN patients. Future research should focus on the longitudinal relationship between obesity and CIPN, and robust interventions to address the multifaceted issues faced by cancer survivors.
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
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/m2. 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.
Ewertz, Marianne; Qvortrup, Camilla; Eckhoff, Lise
BACKGROUND: Chemotherapy with taxanes and platinum compounds has resulted in substantial survival benefits both in adjuvant and metastatic settings. However, as a side effect, such chemotherapy may cause peripheral neuropathy (CIPN) which may result in discontinuation of treatment, and if it pers......BACKGROUND: Chemotherapy with taxanes and platinum compounds has resulted in substantial survival benefits both in adjuvant and metastatic settings. However, as a side effect, such chemotherapy may cause peripheral neuropathy (CIPN) which may result in discontinuation of treatment...
Full Text Available Accumulating evidence suggests that neural-immune interactions are involved in the development of painful chemotherapy-induced peripheral neuropathy, particularly through the increased release of proinflammatory cytokines. The purpose of this study was used to evaluate levels of interleukin [IL]-6 and IL-6 receptors in women with breast cancer after the conclusion of chemotherapy who either had painful symptoms of chemotherapy-induced peripheral neuropathy (CIPN group, N=20 or did not experience CIPN symptoms (Comparison group, N=20. CIPN participants had significantly higher levels of IL-6 and soluble IL-6R (sIL-6R compared to women without CIPN symptoms (P<.001 for both. In addition, soluble gp130, which blocks the IL-6/sIL-6R complex from binding to gp130 within the cellular membrane, was significantly lower (P<.01. Circulating concentrations of sIL-6R were inversely correlated with the density of IL-6R on the cell surface of monocytes in the total sample (r=−.614,P=.005. These findings suggest that IL-6 transsignaling may be an important biological mechanism associated with the persistence of painful CIPN symptoms, with potential implications for symptom management and research.
Talita Cassanta Costa
Full Text Available OBJECTIVE: To identify scientific studies and to deepen the knowledge of peripheral neuropathies induced by chemotherapy antineoplastic, seeking evidence for assistance to cancer patients. METHOD: 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. RESULTS: 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. CONCLUSION: 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.
Liu, Chang-Ning; Berryman, Edwin; Zakur, David; Shoieb, Ahmed M; Pardo, Ingrid D; Boucher, Magalie; Somps, Chris J; Bagi, Chedo M; Cook, Jon C
Chemotherapy-induced peripheral neuropathy (CiPN) is a frequent adverse effect in patients and a leading safety consideration in oncology drug development. Although behavioral assessment and microscopic examination of the nerves and dorsal root ganglia can be incorporated into toxicity studies to assess CiPN risk, more sensitive and less labor-intensive endpoints are often lacking. In this study, rats and mice administered vincristine (75 μg kg-1 day-1 , i.p., for 10 days in rats and 100 μg kg-1 day-1 , i.p., for 11 days in mice, respectively) were employed as the CiPN models. Behavioral changes were assessed during the dosing phase. At necropsy, the sural or sciatic nerve was harvested from the rats and mice, respectively, and assessed for mechanical and histopathological endpoints. It was found that the maximal load and the load/extension ratio were significantly decreased in the nerves collected from the animals dosed with vincristine compared with the vehicle-treated animals (P < 0.05). Additionally, the gait analysis revealed that the paw print areas were significantly increased in mice (P < 0.01), but not in rats following vincristine administration. Light microscopic histopathology of the nerves and dorsal root ganglia were unaffected by vincristine administration. We concluded that ex vivo mechanical properties of the nerves is a sensitive endpoint, providing a new method to predict CiPN in rodent. Gait analysis may also be a useful tool in these pre-clinical animal models. Copyright © 2017 John Wiley & Sons, Ltd.
Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN characterized by loss of sensory sensitivity and pain in hands and feet is the major dose-limiting toxicity of many chemotherapeutics. At present, there are no FDA-approved treatments for CIPN. The anti-diabetic drug metformin is the most widely used prescription drug in the world and improves glycemic control in diabetes patients. There is some evidence that metformin enhances the efficacy of cancer treatment. The aim of this study was to test the hypothesis that metformin protects against chemotherapy-induced neuropathic pain and sensory deficits. Mice were treated with cisplatin together with metformin or saline. Cisplatin induced increased sensitivity to mechanical stimulation (mechanical allodynia as measured using the von Frey test. Co-administration of metformin almost completely prevented the cisplatin-induced mechanical allodynia. Co-administration of metformin also prevented paclitaxel-induced mechanical allodynia. The capacity of the mice to detect an adhesive patch on their hind paw was used as a novel indicator of chemotherapy-induced sensory deficits. Co-administration of metformin prevented the cisplatin-induced increase in latency to detect the adhesive patch indicating that metformin prevents sensory deficits as well. Moreover, metformin prevented the reduction in density of intra-epidermal nerve fibers (IENFs in the paw that develops as a result of cisplatin treatment. We conclude that metformin protects against pain and loss of tactile function in a mouse model of CIPN. The finding that metformin reduces loss of peripheral nerve endings indicates that mechanism underlying the beneficial effects of metformin includes a neuroprotective activity. Because metformin is widely used for treatment of type II diabetes, has a broad safety profile, and is currently being tested as an adjuvant drug in cancer treatment, clinical translation of these findings could be rapidly achieved.
Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is a frequently encountered complication. It can result from a host of agents. Various modalities of treatment have been advocated, of which a novel method is radio frequency ablation. A 63-year-old male, a case of carcinoma prostrate with bone metastases, presented with tingling and numbness in right upper limb. He was given morphine, gabapentin and later switched to pregabalin, but medications provided only minor relief. Initially he was given stellate ganglion block, then radiofrequency ablation of dorsal root ganglion was done, but it failed to provide complete relief. Pulsed radiofrequency ablation (PRF was then done for 90 seconds; two cycles each in both ulnar and median nerve. After the procedure the patient showed improvement in symptoms within four to five hours and 80% relief in symptoms. We conclude that PRF can be used for the treatment of drug resistant CIPN.
Ezendam, N.P.M.; Pijlman, B.M.; Bhugwandass, C.; Pruijt, J.F.; Mols, F.; Vos, M.C.; Pijnenborg, J.M.; van de Poll-Franse, L.
Objective This study assessed the prevalence and risk factors of chemotherapy-induced peripheral neuropathy, and its impact on health-related quality of life among ovarian cancer survivors, 2–12 years after diagnosis. Methods Women (n = 348) diagnosed with ovarian cancer between 2000 and 2010, as
Knoerl, Robert; Dudley, William N; Smith, Gloria; Bridges, Celia; Kanzawa-Lee, Grace; Lavoie Smith, Ellen M
Because numerous barriers hinder the assessment and management of chemotherapy-induced peripheral neuropathy in clinical practice, the Carevive Care Planning System, a novel Web-based platform, was developed to address these barriers. It provides patients an opportunity to report their symptoms before their clinic visit and generates customizable care plans composed of evidence-based management strategies. The purpose of this study was to evaluate patient and provider perspectives of feasibility, usability, acceptability, and satisfaction with the Carevive platform. We used a single-arm, pretest/posttest, prospective design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy and six advanced practice providers from an academic hospital. At three consecutive clinical visits, patients reported their neuropathy symptoms on a tablet via the Carevive system. The Diffusion of Innovations Theory served as an overarching evaluation framework. The Carevive platform was feasible to use. However, patients had higher ratings of usability, acceptability, and satisfaction with the platform than did the providers, who disliked the amount of time required to use the platform and had difficulty logging into Carevive. If issues regarding provider dissatisfaction can be addressed, the Carevive platform may aid in the screening of neuropathy symptoms and facilitate the use of evidence-based management strategies.
McCrary, J Matt; Goldstein, David; Boyle, Frances; Cox, Keith; Grimison, Peter; Kiernan, Matthew C; Krishnan, Arun V; Lewis, Craig R; Webber, Kate; Baron-Hay, Sally; Horvath, Lisa; Park, Susanna B
Chemotherapy-induced peripheral neuropathy (CIPN) is a prominent side effect of the treatment of cancer. Despite this frequent complication, there has been no comprehensive review and quality appraisal of CIPN assessments. The purpose of this study is to provide a definitive quality appraisal of CIPN assessment strategies for clinical use. Relevant studies were identified through database searches of Medline, Embase, CINAHL, and Cochrane. CIPN assessment strategies from included articles were extracted and initially rated by an oncologist and neurophysiologist according to criteria related to assessment depth, comprehensiveness, appropriateness, and reliability. The six highest scoring assessment strategies were the focus of a two-round Delphi survey of a working party of 32 physicians, nurses, and consumers to achieve consensus on the highest rated assessments for each criterion. The database search yielded 117 distinct CIPN assessments that were extracted from 2373 articles. Three patient-reported outcome surveys and three clinician-based assessments were included in the Delphi survey. No consensus was generated regarding the best overall CIPN assessment, although good (≥70%) consensus was achieved regarding the best assessment within each criterion. The Participant Neurotoxicity Questionnaire (PNQ) was rated the highest overall and patient-reported outcome (PRO) assessment, while the Total Neuropathy Score clinical version (TNSc) was the highest rated clinician-based assessment. A diverse range of CIPN assessments currently exists. While several assessments assess CIPN symptoms with adequate comprehensiveness, depth, language, and feasibility, the consensus 'gold standard' clinical assessment remains to be established.
Schröder, Sven; Beckmann, Kathrin; Franconi, Giovanna; Meyer-Hamme, Gesa; Friedemann, Thomas; Greten, Henry Johannes; Rostock, Matthias; Efferth, Thomas
Chemotherapy-induced neuropathy (CIPN) has a relevant impact on the quality of life of cancer patients. There are no curative conventional treatments, so further options have to be investigated. We conducted a systematic review in English and Chinese language databases to illuminate the role of medical herbs. 26 relevant studies on 5 single herbs, one extract, one receptor-agonist, and 8 combinations of herbs were identified focusing on the single herbs Acorus calamus rhizoma, Cannabis sativa...
Lu, Zhaoxue; Moody, Jennifer; Marx, Benjamin L; Hammerstrom, Tracy
Complementary and alternative medicine is increasingly integrated into cancer care. We sought detail on the treatment of chemotherapy-induced peripheral neuropathy (CIPN) with acupuncture and oriental medicine (AOM) by surveying practitioners at integrative oncology (IO) sites across the United States. Online survey of licensed acupuncturists. IO sites in the United States. Fifteen licensed acupuncturists who completed the survey between February 2014 and June 2014. Demographics, IO setting characteristics, AOM treatment characteristics, and practitioner-reported outcomes. Respondents reported an average of 31.3 ± 17.2 patients per week, and one-third (10.1 mean; 7.2 standard deviation [SD]) were treated for CIPN. Medical doctors (86.7%) were the most common providers with whom respondents worked. Traditional Chinese medicine style acupuncture was utilized by a majority of respondents (86.7%), and the most commonly used points were local, typically in the hands and feet, such as Ba Feng, Ba Xie, LV3, and LI4. In addition to acupuncture, nutritional advice was the most frequent auxiliary modality provided by respondents (85.7%). On average, respondents provided 12.75 ± 4.17 treatments for CIPN patients, and a majority (53%) reported treating patients once per week. Timing of the treatments relative to chemotherapy infusion was evenly distributed between "1-2 days after infusion" (60%), "at time of infusion" (53.3%), and "1-2 days before infusion" (46.7%). Sixty percent of respondents rated outcomes as "moderately successful with moderate improvement seen." This survey provides detail regarding IO sites using acupuncture for CIPN as well as real-world treatment patterns, including common point combinations, visit characteristics, and practitioner-reported outcomes. This information contributes to the emerging evidence on the use of acupuncture to address unmet needs of CIPN patients, and supports the development of best practice guidelines for the treatment
Schröder, Sven; Beckmann, Kathrin; Franconi, Giovanna; Greten, Henry Johannes; Rostock, Matthias; Efferth, Thomas
Chemotherapy-induced neuropathy (CIPN) has a relevant impact on the quality of life of cancer patients. There are no curative conventional treatments, so further options have to be investigated. We conducted a systematic review in English and Chinese language databases to illuminate the role of medical herbs. 26 relevant studies on 5 single herbs, one extract, one receptor-agonist, and 8 combinations of herbs were identified focusing on the single herbs Acorus calamus rhizoma, Cannabis sativa fructus, Chamomilla matricaria, Ginkgo biloba, Salvia officinalis, Sweet bee venom, Fritillaria cirrhosae bulbus, and the herbal combinations Bu Yang Huan Wu, modified Bu Yang Huan Wu plus Liuwei Di Huang, modified Chai Hu Long Gu Mu Li Wan, Geranii herba plus Aconiti lateralis praeparata radix , Niu Che Sen Qi Wan (Goshajinkigan), Gui Zhi Jia Shu Fu Tang (Keishikajutsubuto), Huang Qi Wu Wu Tang (Ogikeishigomotsuto), and Shao Yao Gan Cao Tang (Shakuyakukanzoto). The knowledge of mechanism of action is still limited, the quality of clinical trials needs further improvement, and studies have not yielded enough evidence to establish a standard practice, but a lot of promising substances have been identified. While CIPN has multiple mechanisms of neuronal degeneration, a combination of herbs or substances might deal with multiple targets for the aim of neuroprotection or neuroregeneration in CIPN. PMID:23983777
Full Text Available Chemotherapy-induced neuropathy (CIPN has a relevant impact on the quality of life of cancer patients. There are no curative conventional treatments, so further options have to be investigated. We conducted a systematic review in English and Chinese language databases to illuminate the role of medical herbs. 26 relevant studies on 5 single herbs, one extract, one receptor-agonist, and 8 combinations of herbs were identified focusing on the single herbs Acorus calamus rhizoma, Cannabis sativa fructus, Chamomilla matricaria, Ginkgo biloba, Salvia officinalis, Sweet bee venom, Fritillaria cirrhosae bulbus, and the herbal combinations Bu Yang Huan Wu, modified Bu Yang Huan Wu plus Liuwei Di Huang, modified Chai Hu Long Gu Mu Li Wan, Geranii herba plus Aconiti lateralis praeparata radix , Niu Che Sen Qi Wan (Goshajinkigan, Gui Zhi Jia Shu Fu Tang (Keishikajutsubuto, Huang Qi Wu Wu Tang (Ogikeishigomotsuto, and Shao Yao Gan Cao Tang (Shakuyakukanzoto. The knowledge of mechanism of action is still limited, the quality of clinical trials needs further improvement, and studies have not yielded enough evidence to establish a standard practice, but a lot of promising substances have been identified. While CIPN has multiple mechanisms of neuronal degeneration, a combination of herbs or substances might deal with multiple targets for the aim of neuroprotection or neuroregeneration in CIPN.
Schröder, Sven; Beckmann, Kathrin; Franconi, Giovanna; Meyer-Hamme, Gesa; Friedemann, Thomas; Greten, Henry Johannes; Rostock, Matthias; Efferth, Thomas
Chemotherapy-induced neuropathy (CIPN) has a relevant impact on the quality of life of cancer patients. There are no curative conventional treatments, so further options have to be investigated. We conducted a systematic review in English and Chinese language databases to illuminate the role of medical herbs. 26 relevant studies on 5 single herbs, one extract, one receptor-agonist, and 8 combinations of herbs were identified focusing on the single herbs Acorus calamus rhizoma, Cannabis sativa fructus, Chamomilla matricaria, Ginkgo biloba, Salvia officinalis, Sweet bee venom, Fritillaria cirrhosae bulbus, and the herbal combinations Bu Yang Huan Wu, modified Bu Yang Huan Wu plus Liuwei Di Huang, modified Chai Hu Long Gu Mu Li Wan, Geranii herba plus Aconiti lateralis praeparata radix , Niu Che Sen Qi Wan (Goshajinkigan), Gui Zhi Jia Shu Fu Tang (Keishikajutsubuto), Huang Qi Wu Wu Tang (Ogikeishigomotsuto), and Shao Yao Gan Cao Tang (Shakuyakukanzoto). The knowledge of mechanism of action is still limited, the quality of clinical trials needs further improvement, and studies have not yielded enough evidence to establish a standard practice, but a lot of promising substances have been identified. While CIPN has multiple mechanisms of neuronal degeneration, a combination of herbs or substances might deal with multiple targets for the aim of neuroprotection or neuroregeneration in CIPN.
Wolf, S.L.; Barton, D.L.; Qin, R.; Wos, E.J.; Sloan, J.A.; Liu, H.; Aaronson, N.K.; Satele, D.V.; Mattar, B.I.; Green, N.B.; Loprinzi, C.L.
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is characterized by numbness, tingling, and shooting/burning pain. This analysis was performed to describe the relationship between numbness, tingling, and shooting/burning pain in patients with CIPN, as reported using the EORTC
Desideri, Isacco; Francolini, Giulio; Becherini, Carlotta; Terziani, Francesca; Delli Paoli, Camilla; Olmetto, Emanuela; Loi, Mauro; Perna, Marco; Meattini, Icro; Scotti, Vieri; Greto, Daniela; Bonomo, Pierluigi; Sulprizio, Susanna; Livi, Lorenzo
Chemotherapy-induced peripheral neuropathy (CIPN) is a major clinical problem associated with a number of cytotoxic agents. OPERA® (GAMFARMA srl, Milan, Italy) is a new dietary supplement where α-lipoic acid, Boswellia Serrata, methylsulfonylmethane and bromelain are combined in a single capsule. The aim of this prospective study was to determine the efficacy and safety of OPERA® supplementation in a series of patients affected by CIPN. We selected 25 subjects with CIPN evolving during or after chemotherapy with potentially neurotoxic agents. Patients were enrolled at the first clinical manifestation of neuropathy. CIPN was assessed at the enrollment visit and subsequently repeated every 3 weeks until 12 weeks. Primary endpoint was the evaluation of changes of measured scores after 12 weeks of therapy compared to baseline evaluation. Secondary endpoints were the evaluation of neuropathy reduction at 12 weeks after beginning of therapy with OPERA®. Analysis of VAS data showed reduction in pain perceived by patients. According to NCI-CTC sensor and motor score, mISS scale and TNSc scale, both pain and both sensor and motor neuropathic impairment decreased after 12 weeks of treatments. Treatment with OPERA supplement was well tolerated; no increase in the toxicity profile of any of the therapeutic regimen that the patients were undergoing was reported. OPERA® was able to improve CIPN symptoms in a prospective series of patients treated with neurotoxic chemotherapy, with no significant toxicity or interaction. Prospective RCT in a selected patients' population is warranted to confirm its promising activity.
Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is the most common neurological complication in cancer treatment and probably the most common toxic neuropathy in our environment. The aim of the study was to assess the incidence and discomfort caused by neuropathic symptoms in children treated for hematologic cancers. The study included all children admitted to the pediatric oncology service at the University Hospital Center “Mother Teresa”, Tirana, by the year 2011 – 2013 divided in three diagnosis groups: acute lymphoblastic leukemia, Hodgkin and non-Hodgkin’s lymphoma, or other solid tumors. In a prospective cohort setting, data were collected by standard questionnaire for symptoms and signs of neurological damage, according to The Pediatric - Modified Total Neuropathy Scale (Ped - mTNS, as well as clinical evaluation of pin sensibility, vibration sensibility, muscle strength and deep tendon reflexes (DTR. The results obtained from Ped-mTNS, showed the high incidence of sensory and motor symptoms as well as functional deficits in balance and manual dexterity in children treated with anticancer drugs. Ped-mTNS scores, as the first measure designed to assess CIPN in school-aged children, are significantly higher for children undergoing neurotoxic chemotherapy. Even though the neuropathy in these children was relatively mild, it was associated with functional deficits in balance and manual dexterity, suggesting clinical importance. An important limiting factor of this study is the exclusion of children younger than 5 years old, whom discomfort is evident but not properly evaluated.
Yilmaz, Eser; Gold, Michael S
We recently demonstrated, in a rat model of chemotherapy-induced peripheral neuropathy (CIPN), that there is a significant decrease in the duration of the depolarization-evoked Ca(2+) transient in isolated somata of putative nociceptive afferents innervating the glabrous skin of the hindpaw, but no change in transient magnitude or the resting concentration of intracellular Ca(2+) ([Ca(2+)]i). Because the Na(+)-Ca(2+) exchanger (NCX) only contributes to the regulation of the duration of the evoked Ca(2+) transient, in putative nociceptive dorsal root ganglion (DRG) neurons, we hypothesized that an increase in NCX activity underlies the CIPN-induced change in this subpopulation of neurons. Acutely dissociated retrogradely labeled sensory neurons from naïve, vehicle-, and paclitaxel-treated rats were studied with fura-2 based Ca(2+) imaging. There was no difference in the relative level of NCX activity between glabrous neurons from paclitaxel-treated or control rats. However, in contrast to the relatively large and long lasting Ca(2+) transients needed to evoke NCX activity in neurons from naïve rats, there was evidence of resting NCX activity in glabrous neurons from both vehicle- and paclitaxel-treated rats. More interestingly, there was a paclitaxel-induced increase in NCX activity in putative nociceptive neurons innervating the thigh, neurons in which there is no evidence of a change in the depolarization-induced Ca(2+) transient, or a body site in which there was a change in nociceptive threshold. Furthermore, while the majority of NCX activity in glabrous neurons is sensitive to the NCX3-preferring blocker KB-R7943, the increase in NCX activity in thigh neurons was resistant to KB-R7943 but sensitive to the NCX1-preferring blocker SEA0400. These results suggest that a mechanism(s) other than NCX underlies the paclitaxel-induced decrease in the duration of the evoked Ca(2+) transient in putative nociceptive glabrous skin neurons. However, the compensatory
The maintenance of cisplatin- and paclitaxel-induced mechanical and cold allodynia is suppressed by cannabinoid CB₂ receptor activation and independent of CXCR4 signaling in models of chemotherapy-induced peripheral neuropathy.
Deng, Liting; Guindon, Josée; Vemuri, V Kiran; Thakur, Ganesh A; White, Fletcher A; Makriyannis, Alexandros; Hohmann, Andrea G
Chemotherapeutic agents produce dose-limiting peripheral neuropathy through mechanisms that remain poorly understood. We previously showed that AM1710, a cannabilactone CB₂ agonist, produces antinociception without producing central nervous system (CNS)-associated side effects. The present study was conducted to examine the antinociceptive effect of AM1710 in rodent models of neuropathic pain evoked by diverse chemotherapeutic agents (cisplatin and paclitaxel). A secondary objective was to investigate the potential contribution of alpha-chemokine receptor (CXCR4) signaling to both chemotherapy-induced neuropathy and CB₂ agonist efficacy. AM1710 (0.1, 1 or 5 mg/kg i.p.) suppressed the maintenance of mechanical and cold allodynia in the cisplatin and paclitaxel models. Anti-allodynic effects of AM1710 were blocked by the CB₂ antagonist AM630 (3 mg/kg i.p.), but not the CB1 antagonist AM251 (3 mg/kg i.p.), consistent with a CB₂-mediated effect. By contrast, blockade of CXCR4 signaling with its receptor antagonist AMD3100 (10 mg/kg i.p.) failed to attenuate mechanical or cold hypersensitivity induced by either cisplatin or paclitaxel. Moreover, blockade of CXCR4 signaling failed to alter the anti-allodynic effects of AM1710 in the paclitaxel model, further suggesting distinct mechanisms of action. Our results indicate that activation of cannabinoid CB₂ receptors by AM1710 suppresses both mechanical and cold allodynia in two distinct models of chemotherapy-induced neuropathic pain. By contrast, CXCR4 signaling does not contribute to the maintenance of chemotherapy-induced established neuropathy or efficacy of AM1710. Our studies suggest that CB₂ receptors represent a promising therapeutic target for the treatment of toxic neuropathies produced by cisplatin and paclitaxel chemotherapeutic agents.
The maintenance of cisplatin- and paclitaxel-induced mechanical and cold allodynia is suppressed by cannabinoid CB2 receptor activation and independent of CXCR4 signaling in models of chemotherapy-induced peripheral neuropathy
Full Text Available Abstract Background Chemotherapeutic agents produce dose-limiting peripheral neuropathy through mechanisms that remain poorly understood. We previously showed that AM1710, a cannabilactone CB2 agonist, produces antinociception without producing central nervous system (CNS-associated side effects. The present study was conducted to examine the antinociceptive effect of AM1710 in rodent models of neuropathic pain evoked by diverse chemotherapeutic agents (cisplatin and paclitaxel. A secondary objective was to investigate the potential contribution of alpha-chemokine receptor (CXCR4 signaling to both chemotherapy-induced neuropathy and CB2 agonist efficacy. Results AM1710 (0.1, 1 or 5 mg/kg i.p. suppressed the maintenance of mechanical and cold allodynia in the cisplatin and paclitaxel models. Anti-allodynic effects of AM1710 were blocked by the CB2 antagonist AM630 (3 mg/kg i.p., but not the CB1 antagonist AM251 (3 mg/kg i.p., consistent with a CB2-mediated effect. By contrast, blockade of CXCR4 signaling with its receptor antagonist AMD3100 (10 mg/kg i.p. failed to attenuate mechanical or cold hypersensitivity induced by either cisplatin or paclitaxel. Moreover, blockade of CXCR4 signaling failed to alter the anti-allodynic effects of AM1710 in the paclitaxel model, further suggesting distinct mechanisms of action. Conclusions Our results indicate that activation of cannabinoid CB2 receptors by AM1710 suppresses both mechanical and cold allodynia in two distinct models of chemotherapy-induced neuropathic pain. By contrast, CXCR4 signaling does not contribute to the maintenance of chemotherapy-induced established neuropathy or efficacy of AM1710. Our studies suggest that CB2 receptors represent a promising therapeutic target for the treatment of toxic neuropathies produced by cisplatin and paclitaxel chemotherapeutic agents.
... Tooth disorders include extreme weakening and wasting of muscles in the lower legs and feet, gait abnormalities, loss of tendon reflexes, and numbness in the lower limbs. top How is peripheral neuropathy diagnosed? The symptoms ...
... exposure to toxins. One of the most common causes is diabetes mellitus. People with peripheral neuropathy generally describe the ... thyroid (hypothyroidism). In a number of cases, no cause can be identified ... include: Diabetes mellitus, especially if your sugar levels are poorly ...
Wolf, Sherry L; Barton, Debra L; Qin, Rui; Wos, Edward J; Sloan, Jeff A; Liu, Heshan; Aaronson, Neil K; Satele, Daniel V; Mattar, Bassam I; Green, Nathan B; Loprinzi, Charles L
Chemotherapy-induced peripheral neuropathy (CIPN) is characterized by numbness, tingling, and shooting/burning pain. This analysis was performed to describe the relationship between numbness, tingling, and shooting/burning pain in patients with CIPN, as reported using the EORTC QLQ-CIPN20 (CIPN20). Baseline CIPN20 data were provided for all patients on a prospective trial designed to treat patients with bothersome CIPN. Baseline frequencies for the items on the CIPN20 are primarily described by descriptive statistics and histograms, with correlational analyses between individual items. A majority of the 199 patients accrued to this study reported "quite a bit" to "very much" numbness (57%) or tingling (63%) in the hands compared to "a little" or "not at all" (numbness (43%), tingling (38%)). Fewer patients reported "quite a bit" to "very much" shooting/burning pain in the hands (18%). Numbness and tingling in the hands were highly correlated (r = 0.69), while neither were highly correlated with shooting/burning pain. Similar results were observed in the feet. More severe ratings for tingling and shooting/burning pain were ascribed to the lower extremities, as opposed to the upper extremities. In patients with CIPN, severe sensory neuropathy symptoms (numbness, tingling) commonly exist without severe neuropathic pain symptoms (shooting/burning pain), while the reverse is not common. Symptoms in the feet should be evaluated distinctly from those in the hands as the experience of symptoms is not identical, for individual patients, in upper versus lower extremities.
Zanville, Noah R; Nudelman, Kelly N H; Smith, Dori J; Von Ah, Diane; McDonald, Brenna C; Champion, Victoria L; Saykin, Andrew J
To describe the impact of chemotherapy-induced peripheral neuropathy symptoms (CIPN-sx) on breast cancer survivors' (BCS) perceived ability to work post-treatment. The sample included 22 chemotherapy-treated (Ctx+) and 22 chemotherapy-naïve (Ctx-) female BCS. Data was collected at the following three time points: baseline (post-surgery, pre-chemotherapy), 1 month (1 M) post-chemotherapy, and approximately 1 year (1 Y) later. The presence, frequency, number, and severity of CIPN-sx were self-reported using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity questionnaire (FACT/GOG-Ntx) version 4, a validated 11-item CIPN measure. Perceived ability to work was measured using an item from the Functional Well-Being subscale of the FACT/GOG-Ntx. At 1 Y, more than 50 % of Ctx+ reported discomfort, numbness, or tingling in their hands or feet; weakness; or difficulty feeling small objects. The presence, number, and severity of these symptoms were correlated with being less able to work for Ctx+ at 1 M but not 1 Y. Results of a regression analysis using CIPN-sx to predict work ability found that models combining (1) hand numbness and trouble feeling small objects, (2) trouble buttoning buttons and trouble feeling small objects, (3) foot numbness and foot pain, (4) foot numbness and trouble walking, and (5) trouble hearing and hand pain each predicted survivors who were "not at all" able to work at 1 M. Unresolved CIPN-sx may play a role in challenges working for BCS post-treatment. These findings highlight the need for research to explore the impact that CIPN-sx have on BCS' ability to work, as well as the development of interventions to improve work function in BCS with CIPN-sx.
Valentina Van Boekel
Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.
Ventzel, Lise; Jensen, Anders B; Jensen, Anni R; Jensen, Troels S; Finnerup, Nanna B
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer therapy. This study evaluates symptoms of CIPN and CIPN-related pain and its influence on psychological functioning and potential predictors of chronic CIPN and pain. In this large prospective questionnaire study, 174 patients receiving adjuvant oxaliplatin or docetaxel were consecutively included. Patients were asked to complete a questionnaire with validated questions on peripheral neuropathy, pain, anxiety and depression, and quality of life at baseline, after the first cycle, halfway through therapy, and 1 year after baseline. Chronic CIPN symptoms (tingling and/or numbness) in the feet at 1-year follow-up were present in 63.6% of patients without preexisting neuropathy in the oxaliplatin group and in 44.8% in the docetaxel group, whereas pain in hands and feet was found in 31.3% and 35.1%, respectively. Both groups had significantly different pain profiles, and persistent pain in the docetaxel group was found to have effect on psychological function. Cumulative dose predicted oxaliplatin-induced neuropathy (P = 0.004), whereas endocrine therapy predicted peripheral pain in the docetaxel group (P = 0.04). There are important differences in acute neuropathic symptoms and chronic pain profiles in patients after oxaliplatin and docetaxel treatment. It is, however, important to recognize that chronic peripheral pain may be unrelated to neuropathy and can be caused by concomitant treatments. Future studies should focus on characterizing and distinguishing CIPN-related pain from other types of pain to determine the best outcome measures for trials on prevention or relief.
Zheng, H; Xiao, W H; Bennett, G J
Many of the most effective anti-cancer drugs induce a dose-limiting peripheral neuropathy that compromises therapy. Evidence from animal models of chemotherapy-induced painful peripheral neuropathy produced by the taxane agent, paclitaxel, and the platinum-complex agent, oxaliplatin, indicate that they produce neuropathy via a common mechanism-a toxic effect on the mitochondria in primary afferent sensory neurons. Bortezomib is from the proteasome-inhibitor class of chemotherapeutics. It also produces a dose-limiting peripheral neuropathy, but its effects on neuronal mitochondria are unknown. To investigate this, we developed a model of bortezomib-induced painful peripheral neuropathy in the rat and assessed mitochondrial function (respiration and ATP production) in sciatic nerve samples harvested at two time points: day 7, which is three days after treatment and before pain appears, and day 35, which is one month post-treatment and the time of peak pain severity. We found significant deficits in Complex I-mediated and Complex II-mediated respiration, and in ATP production at both time points. Prophylactic treatment with acetyl-L-carnitine, which has previously been shown to prevent paclitaxel- and oxaliplatin-induced mitochondrial dysfunction and pain, completely blocked bortezomib's effects on mitochondria and pain. These results suggest that mitotoxicity may be the core pathology for all chemotherapy-induced peripheral neuropathy and that drugs that protect mitochondrial function may be useful chemotherapy adjuncts. Copyright © 2012 Elsevier Inc. All rights reserved.
Philippi, N; Vinzio, S; Collongues, N; Vix, M; Boehm, N; Tranchant, C; Echaniz-Laguna, A
Peripheral neuropathies sometimes complicate bariatric surgery. We report the detailed clinical, electrophysiological, biological and histological characteristics of five patients who developed peripheral neuropathy after bariatric surgery. Three patients presented with small fiber neuropathy, one presented with axonal polyneuropathy, and one with demyelinating polyradiculoneuropathy. All patients had in common prominent neuropathic pain, massive weight loss, and multiple nutritional deficiencies. The pathophysiology of postbariatric surgery polyneuropathies is complex and involves nutritional, infectious and dysimmune mechanisms. The spectrum of peripheral neuropathies complicating bariatric surgery is wide, and includes pure small fiber neuropathy, axonal polyneuropathy, and demyelinating polyradiculoneuropathy. Treatment is mainly preventive, but sometimes surgical revision is needed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Mathew, David J; Arthur, Anupriya; John, Sheeja Susan
With the advent of more aggressive cytotoxic chemotherapy regimens, the incidence of ocular toxicity due to these drugs is also on the rise. We report a case of Presumed Chemotherapy-Induced optic neuropathy and maculopathy secondary to treatment with cytarabine and daunorubicin for Acute Myeloid Leukaemia (AML). A 50-year-old man with AML developed sudden decrease in vision in his left eye after three cycles of chemotherapy with cytarabine and daunorubicin. He presented to us six weeks later with bilateral optic atrophy and foveal atrophic changes with early bull's eye maculopathy. A diagnosis of presumed chemotherapy-induced optic neuropathy with maculopathy was made, and the patient was put on an alternative chemotherapeutic regimen. There was no further decrease in vision on follow up. To the best of our knowledge, this is the first report of clinically demonstrable macular toxicity in the form of macular atrophic changes and bull's eye maculopathy associated with the use of cytarabine and daunorubicin. Early diagnosis and appropriate management of such cases is imperative to prevent further visual deterioration.
Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed
Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...
P A Sarojini
Full Text Available A 24 year old lady being treated with 300 mg of dapsone daily for dermatitits herpetiformis, developed weakness and wasting of muscles of feet with claw hand deformity and t drop, 2 months tater. Neurological examination and nerve conduction studies conformed the presence of a peripheral motor neuropathy. Dapsone was discontinued and the patient was treated with cotrimatoxazole, gluten-free diet and supportive therapy. This satisfactorily controlled the dermatological lesion without adversely affecting the resolution of her neuropthy. Symptomatic improvement reported by the patient was confirmed by EMG and nerve conduction studies.
Pollock, M; Nukada, H; Frith, R W; Simcock, J P; Allpress, S
Peripheral nerve morphometry was assessed in four patients with Tangier disease. Three patients with a relapsing and remitting multiple mononeuropathy had prominent peripheral nerve demyelination and remyelination with affected internodes clustered along particular nerve fibres. Putative lipid vacuoles were almost exclusively confined in this multifocal neuropathy syndrome to Remak cells. By contrast a fourth patient with a slowly progressive syringomyelia-like neuropathy had advanced peripheral nerve degeneration and a more global distribution of lipid vacuoles within peripheral nerve. A review of Tangier disease in the literature indicated the possibility of additional peripheral nerve syndromes. The clinical heterogeneity raises the possibility of different metabolic errors in Tangier disease or a common metabolic error subject to genetic influences. The results of this study indicate that normal serum cholesterol levels do not exclude a diagnosis of Tangier disease. It is therefore advisable to determine both high density lipoproteins and serum cholesterol levels in patients with undiagnosed multifocal neuropathy or syringomyelia-like syndromes.
Full Text Available Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG. EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG. Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.
Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ...
Schenone, A; Rolando, S; Ferrari, M; Romagnoli, P; Tabaton, M; Mancardi, G L
Two siblings with Cockayne syndrome are reported. In one case a sural nerve biopsy showed a demyelinating peripheral neuropathy with occasional inclusions in Schwann cells made up of electron dense finely granular material intermingled with vacuoles or lamellar structures. The significance, if any, of this accumulated material remains unclear. The presence, in addition, of small finely lamellar intra-axonal osmiophilic bodies suggests an associated axonal involvement.
Mo, Michelle; Erdelyi, Ildiko; Szigeti-Buck, Klara; Benbow, Jennifer H; Ehrlich, Barbara E
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.
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
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.
Callaghan, Brian C.; Price, Ray S.; Chen, Kevin S.; Feldman, Eva L.
Importance Peripheral neuropathy is a prevalent condition that usually warrants a thorough history and examination, but limited diagnostic evaluation. Rare localizations of peripheral neuropathy, however, often require more extensive diagnostic testing and different treatments. Objective To describe rare localizations of peripheral neuropathy, including the appropriate diagnostic evaluation and available treatments. Evidence Review References were identified from PubMed searches with an emphasis on systematic reviews and randomized clinical trials. Articles were also identified through the use of the author's own files. Search terms included common rare neuropathy localizations and their causes, as well as epidemiology, pathophysiology, diagnosis, and treatment. Findings Diffuse, non-length 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, non-length dependent neuropathies are Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and amyotrophic lateral sclerosis (ALS). Effective disease modifying therapies exist for many diffuse, non-length dependent neuropathies including GBS, CIDP, MMN, 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 amyoptrophy (radiculoplexus neuropathy) is lacking. Conclusions and Relevance Recognition of rare localizations of periperhal neuropathy is essential given the implications for diagnostic testing and treatment. Electrodiagnostic studies are an important early step in the
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.
Rosenberg, Casandra J; Watson, James C
Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. To discuss current treatment recommendations for painful diabetic peripheral neuropathy. Literature review. Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared. Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed. The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life. Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. © The International Society for Prosthetics and Orthotics 2014.
Trivedi, Sweety; Pandit, Alak; Ganguly, Goutam; Das, Shyamal Kumar
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
Papanas, Nikolaos; Veletza, Stavroula; Maltezos, Efstratios
Genetic factors may influence the natural course of diabetic peripheral neuropathy and explain some of its variability. The aim of this review was to examine the association between apolipoprotein E (apoE) gene polymorphisms and diabetic peripheral neuropathy. Four relevant studies were identified. The two earlier works provided evidence that the ɛ4 allele is a risk factor for this complication, while the two more recent studies were negative. Important differences in the methodology used and in the populations included are obvious, rendering difficult the comparison between studies. In conclusion, the association between APOE gene polymorphisms and diabetic peripheral neuropathy is still unclear. Available evidence is rather limited and results have so far been contradictory. Future studies should employ more robust methodology, adjusting for potential confounders and for the prevalence of neuropathy in the general population with diabetes. PMID:23056065
Full Text Available Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death world-wide and a further increase in the prevalence as well as mortality of the disease is predicted for coming decades. There is now an increased appreciation for the need to build awareness regarding COPD and to help the thousands of people who suffer from this disease and die prematurely from COPD or its associated complication(s. Peripheral neuropathy in COPD has received scanty attention despite the fact that very often clinicians come across COPD patients having clinical features suggestive of peripheral neuropathy. Electrophysiological tests like nerve conduction studies are required to distinguish between axonal and demyelinating type of disorder that cannot be analyzed by clinical examination alone. However, various studies addressing peripheral neuropathy in COPD carried out so far have included patients with COPD having markedly varying baseline characteristics like severe hypoxemia, elderly patients, those with long duration of illness, etc. that are not uniform across the studies and make it difficult to interpret the results to a consistent conclusion. Almost one-third of COPD patients have clinical evidence of peripheral neuropathy and two-thirds have electrophysiological abnormalities. Some patients with no clinical indication of peripheral neuropathy do have electrophysiological deficit suggestive of peripheral neuropathy. The more frequent presentation consists of a polyneuropathy that is subclinical or with predominantly sensory signs, and the neurophysiological and pathological features of predominantly axonal neuropathy. The presumed etiopathogenic factors are multiple: chronic hypoxia, tobacco smoke, alcoholism, malnutrition and adverse effects of certain drugs.
Full Text Available Identification and characterization of antigens present at the human peripheral nerve is a great challenge in the field of neuroimmunology. The latest investigations are focused on the understanding of the biology of glycoconjugates present at the peripheral nerve, and their immunological reactivity. Increased titers of antibodies that recognize carbohydrate determinants of glycoconjugates (glycolipids and glycoproteins are associated with distinct neuropathic syndromes. There is considerable cross-reactivity among anti-ganglioside antibodies, resulting from shared oligosaccharide epitopes, possibly explaining the overlap in syndromes observed in many affected patients. Sera from patients with neuropathies (GBS, chronic inflammatory demielynating polyneuropathy - CIDP, multifocal motor neuropathy - MMN, cross-react with glycoproteins isolated from human peripheral nerve and from Campylobacter jejuni O:19. The frequency of occurrence of antibodies against these glycoproteins is different, depending of the type of neuropathy. Identification of the cross-reactive glycoproteins and possible additional auto antigens could be useful in laboratory evaluation of peripheral neuropathies and help to develop a more effective therapeutic approach.
Hoeijmakers, Janneke G J; Faber, Catharina G; Merkies, Ingemar S J; Waxman, Stephen G
Peripheral neuropathy can lead to neuropathic pain in a subset of patients. Painful peripheral neuropathy is a debilitating disorder, reflected by a reduced quality of life. Therapeutic strategies are limited and often disappointing, as in most cases targeted treatment is not available. Elucidating pathogenetic factors for pain might provide a target for optimal treatment. Voltage-gated sodium channels NaV1.7-NaV1.9 are expressed in the small-diameter dorsal root ganglion neurons and their axons. By a targeted gene approach, missense gain-of-function mutations of NaV1.7-NaV1.9 have been demonstrated in painful peripheral neuropathy. Functional analyses have shown that these mutations produce a spectrum of pro-excitatory changes in channel biophysics, with the shared outcome at the cellular level of dorsal root ganglion hyperexcitability. Reduced neurite outgrowth may be another consequence of sodium channel mutations, and possible therapeutic strategies include blockade of sodium channels or block of reverse operation of the sodium-calcium exchanger. Increased understanding of the pathophysiology of painful peripheral neuropathy offers new targets that may provide a basis for more effective treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread
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 (pneuropathy 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.
Full Text Available Objective To summarize the clinical features and neuropathological characteristics in patients with vasculitic peripheral neuropathy (VPN. Methods Clinical manifestations, laboratory examination and neuromuscular biopsy characteristics of 11 patients with VPN were retrospectively analyzed. The lesion of nerve, muscle and skin was observed under optical and electron microscope. Immunohistochemical analyses were carried out to detect neurofilament (NF, myelin basic protein (MBP, peripheral myelin protein 22 (PMP22 and S-100 protein (S-100 and further observing the neuropathy of neuraxon, myelin sheath and Schwann cells, and to detect human leukocyte antigen DR (HLA-DR, CD68, CD3 and CD20 to observe inflammatory cell infiltration. Immunofluorescent staining was used to detect the deposition of IgA, IgM, IgG and addiment C3 on vascular wall. The staining of periodic acid-Schiff (PAS, NADH-tetrazolium reductase (NADH-TR and modified Gomori trichrome (MGT were used to judge the myopathy. Results 1 Angiopathies were mainly manifested by small vessels of epineurium and perineurium, and infiltrated inflammatory cells were mainly CD3 + T cells. Three patients had active vasculitis, and 8 patients had non-active vasculitis. Among these 8 patients, 4 patients mainly presented fibrous obliteration of blood vessel, with slight inflammatroy cell infiltration, and the other 4 patients mainly showed perivascular inflammation. 2 Neuropathy: 6 patients had axon degeneration, and 5 patients had axon degeneration associated with demyelination. All of them demonstrated a reduction in myelinated fibers, mainly large diameter myelinated fibers, even on end-stage. 3 Muscle biopsy showed neurogenic atrophy. 4 Clinicopathologic diagnosis: among these 11 patients, 8 patients were diagnosed as systemic vasculitic peripheral neuropathy (SVPN, among whom 5 patients were diagnosed as primary systemic vasculitis [including 1 patient as Churg-Strauss syndrome (CSS, 2 patients as
White, Claire M; van Doorn, Pieter A; Garssen, Marcel P J; Stockley, Rachel C
Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy. A variety of interventions for subjective fatigue are available, but little is known about their efficacy or the likelihood of any adverse effects for people with peripheral neuropathy. To assess the effects of drugs and physical, psychological or behavioural interventions for fatigue in adults or children with peripheral neuropathy. On 5 November 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, LILACS and AMED. We also searched reference lists of all studies identified for inclusion and relevant reviews, and contacted the authors of included studies and known experts in the field to identify additional published or unpublished data. We also searched trials registries for ongoing studies. We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs comparing any form of intervention for fatigue management in adults with peripheral neuropathy with placebo, no intervention or an alternative form of intervention for fatigue. Interventions considered included drugs, pacing and grading of physical activity, general or specific exercise, compensatory strategies such as orthotics, relaxation, counselling, cognitive and educational strategies. Two review authors independently assessed risk of bias and extracted study data. We contacted study authors for additional information. We collected information on adverse events from the included trials. The review includes three trials, which were all at low risk of bias, involving 530 people with peripheral neuropathy. The effects of amantadine from one randomised, double-blind, placebo-controlled, cross-over trial comparing amantadine with placebo for the treatment of fatigue in 80 people with Guillain-Barré syndrome (GBS) were uncertain for the proportion of people achieving
Chekh, Viktor; Soliz, Peter; McGrew, Elizabeth; Barriga, Simon; Burge, Mark; Luan, Shuang
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.
Tanishima, Hiroyuki; Tominaga, Toshiji; Kimura, Masamichi; Maeda, Tsunehiro; Shirai, Yasutsugu; Horiuchi, Tetsuya
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/m2, 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.
Li, Yan; Zhang, Haijun; Zhang, Hongmei; Kosturakis, Alyssa K; Jawad, Abdul Basit; Dougherty, Patrick M
This paper tests the contribution of the toll-like receptors, TLR4 in particular, in the initiation and maintenance of paclitaxel-related chemotherapy-induced peripheral neuropathy. TLR4 and its immediate downstream signaling molecules-myeloid differentiation primary response gene 88 (MyD88) and toll/interleukin 1 receptor domain-containing adapter-inducing interferon-β (TRIF)-were found to be increased in the dorsal root ganglion (DRG) using Western blot by day 7 of paclitaxel treatment. The behavioral phenotype, the increase of both TLR4 and MyD88, was blocked by cotreatment with the TLR4 antagonist lipopolysaccharide-Rhodobacter sphaeroides during chemotherapy. A similar, but less robust, behavioral effect was observed using intrathecal treatment of MyD88 homodimerization inhibitory peptide. DRG levels of TLR4 and MyD88 reduced over the next 2 weeks, whereas these levels remained increased in spinal cord through day 21 following chemotherapy. Immunohistochemical analysis revealed TLR4 expression in both calcitonin gene-related peptide-positive and isolectin B4-positive small DRG neurons. MyD88 was only found in calcitonin gene-related peptide-positive neurons, and TRIF was found in both calcitonin gene-related peptide-positive and isolectin B4-positive small DRG neurons as well as in medium- and large-size DRG neurons. In the spinal cord, TLR4 was only found colocalized to astrocytes but not with either microglia or neurons. Intrathecal treatment with the TLR4 antagonist lipopolysaccharide-R. sphaeroides transiently reversed preestablished chemotherapy-induced peripheral neuropathy mechanical hypersensitivity. These results strongly implicate TLR4 signaling in the DRG and the spinal cord in the induction and maintenance of paclitaxel-related chemotherapy-induced peripheral neuropathy. The toll-like receptor TLR4 and MyD88 signaling pathway could be a new potential therapeutic target in paclitaxel-induced painful neuropathy. Copyright © 2014 American Pain
Reeves, Brandi N; Dakhil, Shaker R; Sloan, Jeff A; Wolf, Sherry L; Burger, Kelli N; Kamal, Arif; Le-Lindqwister, Nguyet A; Soori, Gamini S; Jaslowski, Anthony J; Kelaghan, Joseph; Novotny, Paul J; Lachance, Daniel H; Loprinzi, Charles L
Paclitaxel causes an acute pain syndrome (P-APS), occurring within days after each dose and usually abating within days. Paclitaxel also causes a more classic peripheral neuropathy, which steadily increases in severity with increasing paclitaxel total doses. Little detail is available regarding the natural history of these 2 syndromes, or any relationship between them, although a recent publication does provide natural history data about weekly paclitaxel, supporting an association between the severity of P-APS and eventual peripheral neuropathy symptoms. Patients entering this study were about to receive paclitaxel and carboplatin every 3 weeks. Daily questionnaires were completed for the first week after every chemotherapy dose, and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Chemotherapy-Induced Peripheral Neuropathy 20-item instruments were completed weekly. The P-APS severity peaked on day 4 after the initial chemotherapy dose, with 12%, 29%, 23%, and 36% of patients having maximal pain scores of 0, 1 to 4, 5 or 6, or 7 to 10 during the first week after the first dose of therapy, respectively. Patients with P-APS scores of 0 to 4 with the first dose of chemotherapy had less eventual sensory neuropathy than did patients with P-APS scores of 5 to 10 (P = 0.001). With regard to the more peripheral neuropathy, sensory neuropathy was more problematic than was either motor or autonomic neuropathy. Numbness and tingling were more common components of the sensory neuropathy than was pain. Patients with worse P-APS severities appear to have more eventual chemotherapy-induced peripheral neuropathy. This provides support for the concept that P-APS is a form of nerve pathology. Copyright © 2012 American Cancer Society.
Kambiz, Shoista; Neck, Han; Cosgun, Saniye G; Velzen, M. H N; Janssen, Joseph; Avazverdi, N; Hovius, Steven; Walbeehm, Erik
... diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared thermography was used to assess the rewarming rate after cold exposure on the plantar skin of STZ diabetic rats' hind paws...
Tong, Yanqing; Guo, Hongyang; Han, Bing
Our study aimed to investigate the effects of acupuncture on diabetic peripheral neuropathy. We compared 42 cases treated with acupuncture with 21 cases exposed to sham acupuncture and observed the effects on nerve conduction velocity and a variety of subjective symptoms associated with diabetic peripheral neuropathy. Three of the six measures of motor nerves, and two measures of sensory function, demonstrated significant improvement (p day treatment period in the acupuncture group, while no motor or sensory function significantly improved in the sham acupuncture group. There were also significant differences in vibration perception threshold between the groups (p neuropathy. Copyright 2010 Korean Pharmacopuncture Institute. Published by .. All rights reserved.
May, Jonathan David; Morris, Matthew William John
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. pdiabetic 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 rights reserved.
Full Text Available Relevance. Peripheral neuropathy (PNP in urogenital chlamydia reactive arthritis (CRA is described as single observations, and many clinical and pathogenetic aspects of this lesion of the nervous system remain unclear. Objective of the study: to evaluate the incidence and nature of the clinical course of PNP in CRA, the connection of the nerve and joint injuries, to explore the questions of pathogenetic constructions of this neuropathy, to identify risk factors. Material and methods. We observed 101 patients with CRA, mean age of them was 32 years, disease duration — 4 years, and the male to female ratio — 1 : 1. In 90 % of CRA cases, Chlamydia trochamatis was found in prostatic secretions, in scraps from the urethra, the cervix, the vaginal wall, in 83 % — positive serologic tests for chlamydia infection. Results. Signs of PNP in CRA were in 19 % of patients in the ratio of mononeuropathy to polyneuropathy as 1 : 1, with motor, sensory and mixed disorders in a ratio of 1 : 3 : 6, the presence of autonomic changes in every second patient and more frequent distal localization of the process in the hands, which is influenced by the severity of the articular syndrome, high levels of antichlamydia antibodies in the blood, and the axonal and demyelinating indicators of electroneuromyography — by the severity of urogenital lesions and the presence of Guillain-Barre syndrome. A high rate of arthritis progression is a prognosis-negative sign of PNP course in patients with CRA. The pathogenic constructions of PNP involve the inflammatory immune proteins, disturbances of vascular endothelial function and physicochemical surface rheological properties of the serum. Conclusion. PNP takes place in every fifth patient with CRA, correlates with clinical and laboratory signs of joint disease, and in the future will be useful to identify actively this pathology of the nervous system for the subsequent timely rehabilitation, and CRA
VANDENBERG, LH; LANKAMP, CLAM; DEJAGER, AEJ; NOTERMANS, NC; SODAAR, P; MARRINK, J; DEJONG, HJ; BAR, PR; WOKKE, JHJ
A study was carried out on 135 patients with chronic idiopathic neuropathy (63), neuropathy associated with monoclonal gammopathy (51, including eight with anti-MAG antibody activity) and the Guillain-Barre syndrome (GBS) (21). Serum IgM, IgG and IgA anti-sulphatide antibody titres were compared
Lee, Samuel M.
Peripheral neuropathies such as Charcot-Marie-Tooth disease (CMT) are a group of neurological disorders that affect the peripheral nervous system. Although demyelinating CMT is the most prevalent hereditary peripheral neuropathy, there are currently no effective treatments for patients suffering from this disease. Recent studies by our group and others have provided a link between protein misfolding and demyelinating CMT and indicate that impairment of the proteasome and aggresome-autophagy pathways may contribute to CMT pathogenesis. These studies suggest that targeting protein quality control systems involved in cytoprotection against CMT-associated misfolded proteins could have therapeutic benefits for treating demyelinating CMT. PMID:22482025
Pope, Karl; So, Yuen T; Crane, Julian; Bates, Michael N
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 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 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. Copyright © 2017 Elsevier B.V. All rights reserved.
Tenenbein, M; deGroot, W; Rajani, K R
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.
Tenenbein, M; DeGroot, W; Rajani, K R
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 spec...
Segat, Gabriela C; Manjavachi, Mariane N; Matias, Daiane O; Passos, Giselle F; Freitas, Cristina Setim; Costa, Robson; Calixto, João B
Painful peripheral neuropathy is a common side effect of paclitaxel (PTX). The use of analgesics is an important component for management of PTX-induced peripheral neuropathy (PINP). However, currently employed analgesics have several side effects and are poorly effective. β-caryophyllene (BCP), a dietary selective CB2 agonist, has shown analgesic effect in neuropathic pain models, but its role in chemotherapy-induced neuropathic pain has not yet been investigated. Herein, we used the mouse model of PINP to show the therapeutic effects of BCP in this neuropathy. Male Swiss mice receiving PTX (2 mg kg-1, ip, four alternate days) were treated with BCP (25 mg kg-1, po, twice a day) either during or after PTX administration. Some groups were also pretreated with AM630 (CB2 antagonist, 3 mg kg-1, ip) or AM251 (CB1 antagonist, 1 mg kg-1, ip). Spinal cord samples were collected in different time points to perform immunohistochemical analysis. BCP attenuated the established mechanical allodynia induced by PTX (p < 0.0001) in a CB2-dependent manner. Of note, when given concomitantly with PTX, BCP was able to attenuate the development of PINP (p < 0.0001). Spinal cord immunohistochemistry revealed that preventive treatment with BCP reduced p38 MAPK and NF-κB activation, as well as the increased Iba-1 and IL-1β immunoreactivity promoted by PTX. Our findings show that BCP effectively attenuated PINP, possibly through CB2-activation in the CNS and posterior inhibition of p38 MAPK/NF-κB activation and cytokine release. Taken together, our results suggest that BCP could be used to attenuate the establishment and/or treat PINP. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available Background. Treatment of chemotherapy-induced peripheral neuropathy (CIPN remains a big challenge for oncologists. The aim of this study is to evaluate the effects of Radix Astragali- (RA- based Chinese herbal medicine in the prevention and treatment of oxaliplatin-induced peripheral neuropathy, including the incidence and grading of neurotoxicity, effective percentage, and nerve conduction velocity. Methods. All randomized controlled trials (RCTs were found using PubMed, Cochrane, Springer, China National Knowledge Infrastructure (CNKI, and Wanfang Database of China Science Periodical Database (CSPD by keyword search. Meta-analysis was conducted using RevMan 5.0. Results. A total of 1552 participants were included in 24 trials. Meta-analysis showed the incidence of all-grade neurotoxicity was significantly lower in experimental groups and high-grade neurotoxicity was also significantly less. Effective percentage was significantly higher and sensory nerve conduction velocity was improved significantly, but changes in motor nerve conduction velocity were not statistically significant. No adverse events associated with RA-based intervention were reported. Conclusion. RA-based intervention may be beneficial in relieving oxaliplatin-induced peripheral neuropathy. However, more double-blind, multicenter, large-scale RCTs are needed to support this theory. Trial Registration. PROSPERO International prospective register of systematic reviews has registration number CRD42015019903.
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 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, pneuropathy 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, pdiabetic neuropathy from healthy controls, while the inferior RNFL thickness is able to differentiate those with greater degrees of neuropathy from those with mild or no neuropathy, both with an acceptable level of accuracy. Optical coherence tomography represents a non-invasive technology that aids in detection of retinal structural changes in patients with established diabetic neuropathy. Further refinement of the technique and the analytical approaches may be
Campistol Plana, J; Riverola de Veciana, A; Poo Argüelles, P; Colomer Oferil, J; Moreno Hernández, J
We report a clinical observation of an infant aged 5 months with Cockayne syndrome whose symptomatology included failure to thrive, microcephaly, peripheral neuropathy and elevated level of protein in CSF. More typical signs of this syndrome appeared lately with progeroid facies, photosensitivity and intracranial calcifications that computed tomography revealed at 13 months of age. The early onset of clinical manifestations, the association with peripheral neuropathy, and the high level of protein in CSF are unusual facts that led us to do the differential diagnosis with other demyelinating disorders.
Singh, Randhir; Kishore, Lalit; Kaur, Navpreet
Diabetic neuropathy is a heterogeneous group of disorders with extremely complex pathophysiology and affects both somatic and autonomic components of the nervous system. Neuropathy is the most common chronic complication of diabetes mellitus. Metabolic disruptions in the peripheral nervous system, including altered protein kinase C activity, and increased polyol pathway activity in neurons and Schwann cells resulting from hyperglycemia plays a key role in the development of diabetic neuropathy. These pathways are related to the metabolic and/or redox state of the cell and are the major source of damage. Activation of these metabolic pathways leads to oxidative stress, which is a mediator of hyperglycemia induced cell injury and a unifying theme for all mechanisms of diabetic neuropathy. The therapeutic intervention of these metabolic pathways is capable of ameliorating diabetic neuropathy but therapeutics which target one particular mechanism may have a limited success. Available therapeutic approaches are based upon the agents that modulate pathogenetic mechanisms (glycemic control) and relieve the symptoms of diabetic neuropathy. This review emphasizes the pathogenesis, presently available therapeutic approaches and future directions for the management of diabetic neuropathy. Copyright © 2013 Elsevier Ltd. All rights reserved.
Epplin-Zapf, Thomas; Miller, Clayton; Larkin, Sean; Hermesmeyer, Eduardo; Macy, Jenny; Pellegrini, Marco; Luccarelli, Saverio; Staurenghi, Giovanni; Holmes, Timothy
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.
Rondinelli, Marina Flaksman Curi; Cavalcanti, Ismar Lima; Gonçalves,Odiléa Rangel; Verçosa,Nubia
ABSTRACT BACKGROUND AND OBJECTIVES: Peripheral neuropathy caused by chemotherapeutic drugs is today one of the major limiting factors in cancer pharmacological therapy due to its negative influence in the cancer patient's quality of life. Its incidence varies depending on the pharmacological nature of the therapy used. Peripheral neurotoxicity caused by 5-Fluorouracil was scarcely described, being characterized as rare adverse effect of this drug. The objective of this study is to report a 5...
Kagiava, Alexia; Sargiannidou, Irene; Theophilidis, George; Karaiskos, Christos; Richter, Jan; Bashiardes, Stavros; Schiza, Natasa; Nearchou, Marianna; Christodoulou, Christina; Scherer, Steven S; Kleopa, Kleopas A
Inherited demyelinating peripheral neuropathies are progressive incurable diseases without effective treatment. To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we delivered a lentiviral vector using a single lumbar intrathecal injection and a myelin-specific promoter. The human gene of interest, GJB1, which is mutated in X-linked Charcot-Marie-Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1-null mice, a genetically authentic model of CMT1X that develops a demyelinating peripheral neuropathy. We obtained widespread, stable, and cell-specific expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal roots and peripheral nerves. Behavioral and electrophysiological analysis revealed significantly improved motor performance, quadriceps muscle contractility, and sciatic nerve conduction velocities. Furthermore, treated mice exhibited reduced numbers of demyelinated and remyelinated fibers and fewer inflammatory cells in lumbar motor roots, as well as in the femoral motor and sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene delivery can lead to Schwann cell-specific expression in spinal roots extending to multiple peripheral nerves. This clinically relevant approach improves the phenotype of an inherited neuropathy mouse model and provides proof of principle for treating inherited demyelinating neuropathies.
Background: Chronic anemia in thalassemia patients may cause multiple complications such as bone deformities, growth retardation, and peripheral neuropathy. Aim: To examine the presence of possible electrophysiological changes in children diagnosed with thalassemia and to investigate the clinical factors affecting the ...
Pourmohammadi, Nasir; Alimoradi, Houman; Mehr, Shahram Ejtemaei; Hassanzadeh, Gholamreza; Hadian, Mohammad Reza; Sharifzadeh, Mohammad; Bakhtiarian, Azam; Dehpour, Ahmad Reza
As a cancer chemotherapeutic agent, paclitaxel (Taxol® ) causes dose-related peripheral neuropathy in human beings. The mechanisms underlying this toxicity are currently unknown, and there are no validated treatments for its prevention or control. To assess whether lithium as a pre-treatment and at subtherapeutic dose could prevent the peripheral neuropathy produced by it, rats were treated with paclitaxel (2 mg/kg i.p. every other day for a total of 16 times) and/or lithium chloride (300 mg/l) via water supply. General toxicity and body-weight were measured regularly during the experiment. To evaluate the sensory and motor neuropathy hot-plate, open-field test and nerve conduction velocity were used. In rats treated with only paclitaxel, there was behavioural, electrophysiological and histological evidence of a mixed sensorimotor neuropathy after 16 injections. Lithium robustly reduced the rate of mortality and general toxicity. Paclitaxel-induced sensorimotor neuropathy was significantly improved as indicated by changes in hotplate latency, total distance moved and a significant increase in sciatic, sural and tail sensory or motor nerve conduction velocity. The same results were observed in histopathological examinations; however, dorsal root ganglion neurons did not significantly change in the paclitaxel-treated groups. These results suggest that lithium, at subtherapeutic doses, can prevent both motor and sensory components of paclitaxel neuropathy in rats. Thus, lithium at these doses, as an inexpensive and relatively safe salt, may be useful clinically in preventing the neuropathy induced by paclitaxel treatment. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.
Yorek, Mark Anthony
Peripheral neuropathy affects about 50% of the diabetic population. The manifestations range from pain, numbness, paresthesia and ulceration in the extremities and it is the major cause of non-traumatic amputations. Currently there is no effective treatment for peripheral neuropathy. With the prevalence of obesity and type 2 diabetes and associated complications reaching epidemic levels there is a critical need for finding a treatment to preserve nerve function. This article will review the potential for fish oil as a treatment for diabetic peripheral neuropathy. A through search of the PubMed database was performed and relevant articles on the topic were included in this review. Many studies support a role for fish oil in cardiovascular health. However, less information is available regarding the effect of fish oil on diabetes complications including neuropathy. Pre-clinical studies from my laboratory using diabetic rodent models have demonstrated that fish oil can slow progression and reverse diabetic neuropathy as determined by examining multiple endpoints. Mechanistically fish oil has been shown to have anti-inflammatory properties. Lowering the omega-6/omega-3 fatty acid ratio has been shown to be anti-thrombotic. Moreover, metabolites of eicosapentaenoic and docosahexaenoic acids, the main polyunsaturated fatty acids found in fish oil, commonly referred to as resolvins and neuroprotectin have been shown to be neuroprotective and can stimulate neuron outgrowth in vitro. Additional studies are required but existing data suggests that dietary enrichment with omega-3 fatty acids contained in fish oil may be beneficial treatment for diabetic neuropathy. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Pitcher, Graham M; Ritchie, Jennifer; Henry, James L
The present study was aimed at the issue of whether peripheral nerve injury-induced chronic pain is maintained by supraspinal structures governing descending facilitation to the spinal dorsal horn, or whether altered peripheral nociceptive mechanisms sustain central hyperexcitability and, in turn, neuropathic pain. We examined this question by determining the contribution of peripheral/spinal mechanisms, isolated from supraspinal influence(s), in cutaneous hypersensitivity in an animal model of peripheral neuropathy. Adult rats were spinalized at T8-T9; 8 days later, peripheral neuropathy was induced by implanting a 2-mm polyethylene cuff around the left sciatic nerve. Hind paw withdrawal responses to mechanical or thermal plantar stimulation were evaluated using von Frey filaments or a heat lamp, respectively. Spinalized rats without cuff implantation exhibited a moderate decrease in mechanical withdrawal threshold on ~day 10 (P day 18 (P day 4; P day 10; P neuropathy may have a pathologically relevant role in both inducing and sustaining neuropathic pain. Wiley Periodicals, Inc.
Jusufovic, Mirza; Lygren, Astrid; Aamodt, Anne Hege; Nedregaard, Bård; Kerty, Emilia
Vascular damage in the central hand knob area can mimic peripheral motor nerve deficits. We describe the case of a woman presenting with apparent peripheral neuropathy. Brain magnetic resonance imaging and computed tomography angiography revealed an infarct in the precentral hand knob area, with significant stenosis in the right proximal middle cerebral artery trunk. Subsequent 3-Tesla magnetic resonance imaging of the brain suggested cerebral angiitis. The patient experienced improved hand function following combined glucocorticoid and cyclophosphamide treatment. Vascular damage in the hand knob area should be considered when evaluating peripheral motor nerve deficits in the presence of normal nerve conduction velocities. The diagnosis of cerebral angiitis remains a major challenge for clinicians.
Al-Zuhairy, Ali; Schrøder, Henrik Daa; Plesner, Torben
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. METHODS: 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. RESULTS......: 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...
Liu, Feng; Mao, Ji-Ping; Yan, Xiang
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.
Hansen, C.S.; Jensen, T.M.; Jensen, J.S.
AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy...... and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen......-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy...
Osborne, W L; Holyoake, T L; McQuaker, I G; Parker, A N
We discuss a case with significant progressive peripheral neurological deterioration following administration of both fludarabine and cytarabine as part of the FLA (fludarabine and cytarabine) regime. Of particular interest is that toxicity only occurred during the second course of FLA and sixth course of Ara-C containing chemotherapy. At this point, a new antifungal agent had been commenced, suggesting a possible drug interaction enhancing the risk of known neurological toxicity with this regime.
Full Text Available The mechanisms leading to diabetic peripheral neuropathy are complex and there is no effective drug to treat it. As an active component of several traditional Chinese medicines, trigonelline has beneficial effects on diabetes with hyperlipidemia. The protective effects and the mechanism of trigonelline on diabetic peripheral neuropathy were evaluated in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Rats were divided into four groups at the end of week 2: control, diabetes, diabetes + trigonelline (40 mg/kg, and diabetes + sitagliptin (4 mg/kg. After 48-week treatment, technologies of nerve conduction, cold and hot immersion test, transmission electron microscopy, real-time PCR, and Western blotting were applied. Serum glucose, serum insulin, insulin sensitivity index, lipid parameters, body weight, sciatic nerve conduction velocity, nociception, glucagon-like peptide-1 receptor mRNA and protein, total and phosphorylated p38 mitogen-activated protein kinases protein expression, malonaldehyde content, and superoxide dismutase activity were altered in diabetic rats, and were near control levels treated with trigonelline. Slight micropathological changes existed in sciatic nerve of trigonelline-treated diabetic rats. These findings suggest that trigonelline has beneficial effects for diabetic peripheral neuropathy through glucagon-like peptide-1 receptor/p38 mitogen-activated protein kinases signaling pathway, nerve conduction velocity, antioxidant enzyme activity, improving micropathological changes of sciatic nerve and decreasing lipid peroxidation.
Nagashima, Satoshi; Kiba, Takayoshi; Ogawa, Yoshikazu; Mura, Takuya; Kajiume, Sayoko; Okada, Yuuko; Morii, Nao; Takahashi, Hirotoshi; Ichiba, Yasunori; Yamashiro, Hiroyasu
Here, we report about a 60-year-old woman with metastatic breast cancer who was successfully treated for paclitaxelinduced peripheral neuropathy with duloxetine. She was administered trastuzumab plus paclitaxel(PTX)combination therapy that was ultimately discontinued because of grade 3 peripheral neuropathy detected on day 15, according to the CTCAE (v4.0). She was administered duloxetine on day 90 after the end of the previous therapy because of the peripheral neuropathy. Thereafter, the peripheral neuropathy decreased to grade 1, which enabled PTX administration on her request. Further trials are required to confirm the efficacy of duloxetine.
Elisabeth G Vichaya
Full Text Available While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms of chemotherapy include (i cognitive deficiencies such as problems with attention, memory and executive functioning; (ii fatigue and motivational deficit; and (iii neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.
Rudnicki, Stacy A
Given the ever-increasing problem of obesity, it is not surprising that the number of patients who undergo bariatric surgery continues to rise. For patients who have gastric banding, the amount of food they can consume is limited, and nausea and vomiting may further limit nutritional intake early on. More extensive procedures, such as the Roux-en-Y or biliopancreatic diversion with or without a duodenal switch, not only restrict intake but also limit absorption in the small intestine. As a result, deficiencies in vitamins, minerals, and trace elements may develop, leading to a variety of neurologic complications. The peripheral neuropathies best described with a clear-cut cause are an acute, frequently painful neuropathy or polyradiculoneuropathy associated with thiamine deficiency, and an isolated neuropathy or myeloneuropathy associated with deficiencies of either vitamin B12 or copper. Thiamine deficiency tends to occur in the first weeks or months after surgery, vitamin B12 deficiency may develop at any time from a few years to many years after surgery, and copper deficiency tends to be a fairly late complication, developing several years to many years following surgery. Patients who have undergone bariatric surgery may also have an increased risk of developing focal neuropathies, though these are less clearly related to specific nutritional deficiencies.Ideally, one would like to prevent these neuropathies, but there is no consensus of opinion as to what vitamins and micronutrients need to be taken following bariatric surgery. In addition, many patients who take supplements early on fail to maintain the regimen even though some of the neuropathies can occur fairly late. Supplements frequently recommended include a multivitamin, iron, vitamin D, folic acid, calcium citrate, and vitamin B12. Although thiamine is typically included in a multivitamin, the amount is fairly small, so I recommend adding 100 mg daily for at least the first year. Some have suggested
Valdir Morais de Almeida
Full Text Available ABSTRACT: This report aimed to describe a case of peripheral neuropathy in a copper-deficient goat, and highlights the clinical, and pathological features of the disease. The goat had low body score, hyporexia, alopecia, achromotrichia, left hindlimb protraction, paralysis with dragging of digit and difficulty to stand up and microcytic normochromic anemia. Copper concentration in serum was markedly lower (2.0µmol L-1 whereas the iron serum content was significantly increased (51.0µmol L-1. The main gross alteration was the reduction of the quadriceps vastus laterallis muscle volume. Histologically, there was atrophy of the quadriceps vastus laterallis muscle and presence of satellite cells, infiltration of lymphocytes, macrophages and replacement of the fibers by connective tissue. In the femoral nerve, there was axonal degeneration with myelin sheath expansion and presence of vacuoles, usually in chains and containing axonal debris or macrophages. Clinical, laboratorial and pathologic findings are consistent with peripheral neuropathy due to a severy copper deficiency.
Full Text Available The inherited peripheral neuropathies (IPNs comprise a growing list of genetically heterogeneous diseases. With mutations in more than 80 genes being reported to cause IPNs, a wide spectrum of functional consequences is expected to follow this genotypic diversity. Hence, the search for a common pathomechanism among the different phenotypes has become the holy grail of functional research into IPNs. During the last decade, studies on several affected genes have shown a direct and/or indirect correlation with autophagy. Autophagy, a cellular homeostatic process, is required for the removal of cell aggregates, long-lived proteins and dead organelles from the cell in double-membraned vesicles destined for the lysosomes. As an evolutionarily highly conserved process, autophagy is essential for the survival and proper functioning of the cell. Recently, neuronal cells have been shown to be particularly vulnerable to disruption of the autophagic pathway. Furthermore, autophagy has been shown to be affected in various common neurodegenerative diseases of both the central and the peripheral nervous system including Alzheimer’s, Parkinson’s, and Huntington’s diseases. In this review we provide an overview of the genes involved in hereditary neuropathies which are linked to autophagy and we propose the disruption of the autophagic flux as an emerging common pathomechanism. We also shed light on the different steps of the autophagy pathway linked to these genes. Finally, we review the concept of autophagy being a therapeutic target in IPNs, and the possibilities and challenges of this pathway-specific targeting.
Walker, Melanie; Weiss, Michael D; Distad, B Jane; Samii, Ali
Myotonic dystrophy type 2 (DM2) is a phenotypically heterogeneous multisystem disorder, most dramatically involving the nervous system. Although multisystem involvement is common in this disease, we present a genetically proven DM2 patient with both peripheral neuropathy and blood dyscrasia, previously unreported in the literature, suggesting a distinct phenotype in this population. Routine electrophoresis in DM2 patients with neuropathy is recommended, and implications surrounding the etiology of peripheral neuropathy and paraproteinemia in DM2 are discussed.
Walaa Fadhil Jalal
Full Text Available Diabetic peripheral neuropathy (DPN is the most common complication of type 2 diabetes mellitus. Cranial neuropathies is usually presenting as mononeuropathies coexist with DPN either presented clinically or in subclinical form. The aim of this study is to detect cranial neuropathy in diabetic patients. Eighty three patients with type 2 diabetes mellitus (T2DM with an age range of 30-69 years were included in the study. The study also involved normal healthy persons whose age and gender are harmonized with that of our patients that were deliberated as control group (60 persons. Diabetic patients with DPN had significant difference in age, highly significant difference in the duration of the disease and highly significance difference in BMI had poor glycemic control reflected by high FBS and HbA1c, while lipid profile picture showed insignificant difference when compared with diabetic patients without DPN. Nerve conduction study (sensory and motor showed a significant difference regarding latency, amplitude, and conduction velocity between diabetic patients with DPN and those without DPN. The results of blink reflex showed highly significant difference between diabetic patients and controls.
Rosenberg, N. R.; Vermeulen, M.
Objective: To investigate whether there is an association between chronic peripheral neuropathy and coeliac disease. Methods: The cause of chronic peripheral neuropathy was first investigated in a group of 478 patients. Published reports were then examined systematically for an association between
Fateh, Hamid R; Madani, Seyed Pezhman; Heshmat, Ramin; Larijani, Bagher
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
Emily I Chen
Full Text Available Major advances in early detection and therapy have significantly increased the survival of breast cancer patients. Unfortunately, most cancer therapies are known to carry a substantial risk of adverse long-term treatment-related effects. Little is known about patient susceptibility to severe side effects after chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN is a common side effect of taxanes. Recent advances in genome-wide genotyping and sequencing technologies have supported the discoveries of a number of pharmacogenetic markers that predict response to chemotherapy. However, effectively implementing these pharmacogenetic markers in the clinic remains a major challenge. On the other hand, recent advances in proteomic technologies incorporating mass spectrometry (MS for biomarker discovery show great promise to provide clinically relevant protein biomarkers. In this study, we evaluated the association between protein content in serum exosomes and severity of CIPN. Women with early stage breast cancer receiving adjuvant taxane chemotherapy were assessed with the FACT-Ntx score and serum was collected before and after the taxane treatment. Based on the change in FACT-Ntx score from baseline to 12 month follow-up, we separated patients into two groups: those who had no change (Group 1, N = 9 and those who had a ≥20% worsening (Group 1, N = 8. MS-based proteomics technology was used to identify proteins present in serum exosomes to determine potential biomarkers. Mann-Whitney-Wilcoxon analysis was applied and maximum FDR was controlled at 20%. From the serum exosomes derived from this cohort, we identified over 700 proteins known to be in different subcellular locations and have different functions. Statistical analysis revealed a 12-protein signature that resulted in a distinct separation between baseline serum samples of both groups (q<0.2 suggesting that the baseline samples can predict subsequent neurotoxicity. These toxicity
Yang-Sook Yoo, RN, PhD
Conclusion: Collectively, our results indicate that nurse-led bedside evaluation is a noninvasive and useful method for detecting neurotoxicity and evaluating the patient’s QOL both during and after treatment.
Schröder, Sven; Beckmann, Kathrin; Franconi, Giovanna; Meyer-Hamme, Gesa; Friedemann, Thomas; Greten, Henry Johannes; Rostock, Matthias; Efferth, Thomas
..., Chamomilla matricaria, Ginkgo biloba, Salvia officinalis, Sweet bee venom, Fritillaria cirrhosae bulbus, and the herbal combinations Bu Yang Huan Wu, modified Bu Yang Huan Wu plus Liuwei Di Huang...
Full Text Available 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.
Xue, Hong-Xia; Fu, Wen-Yi; Cui, Hua-Dong; Yang, Li-Li; Zhang, Ning; Zhao, Li-Juan
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 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.
Dukewich, Matthew; Danesh, Arash; Onyima, Chiemeka; Gupta, Anita
Fluoroquinolones are widely prescribed antibiotics, used for various infectious etiologies. These antibiotics carry the possibility of the serious adverse effect of peripheral neuropathy, with a true incidence not known owing to its rare existence. Recently, the Food and Drug Administration (FDA) has required alterations to drug labels to highlight this adverse effect of fluoroquinolones. This is a case report of a single patient at an inpatient neurology service at an urban academic medical center in the United States. The patient is a 20-year-old male, with well-controlled type 1 diabetes mellitus, presenting with a short duration of bilateral lower extremity pain following a 10-day course of levofloxacin for suspected epididymitis. The patient was initially diagnosed with complex regional pain syndrome and treated with a variety of pain medications, including lidocaine infusions, hydromorphone, methadone, and ketamine infusions. After review of the patient's history and limited response to medical management, the patient's condition was reclassified as an adverse effect from fluoroquinolone treatment. Pain of unknown etiology can be perplexing, both for the physician and the patient. Reporting of similar incidents attributed to medication adverse effects will increase the awareness of this type of neuropathy, avoid future cases of misdiagnosis, and enable early detection and treatment.
Conclusions: The GCC FLV can differentiate individuals with diabetic neuropathy from healthy controls, while the inferior RNFL thickness is able to differentiate those with greater degrees of neuropathy from those with mild or no neuropathy, both with an acceptable level of accuracy. Optical coherence tomography represents a non-invasive technology that aids in detection of retinal structural changes in patients with established diabetic neuropathy. Further refinement of the technique and the analytical approaches may be required to identify patients with minimal neuropathy.
Full Text Available Osteomalacia and rickets are important reversible causes of debilitating muscular weakness and bony pains in India among all socio-economic strata and at all ages. Osteomalacia after bariatric surgery is documented in literature. Most reports on osteomalacic weakness note myopathic pattern on electromyography. We present the case of a young obese girl from a good socio-economic status who developed severe muscular weakness after sleeve gastrectomy surgery. The patient was found to have osteomalacia with normal vitamin B12 and folate levels. Electrodiagnostic studies demonstrated neuropathic pattern while radiological tests confirmed osteopenia and Looser′s zones. Specific vitamin D supplementation was associated with improvement though contribution of other micronutrients in diet cannot be ruled out. Relevance of vitamin D deficiency and urgent need for its correction in the population all over the world and especially in Asia is an emerging health issue. Peripheral motor neuropathy is a rare, seldom reported presentation of osteomalacia.
Hayakawa, Katsuhiko [Aikoh Orthopaedic Hospital, Nagoya (Japan); Kobayashi, Shigeru; Suzuki, Katsuji; Yamada, Mitsuko; Kojima, Motohiro
We carried out enhanced MRI for the carpal tunnel syndrome, cubital tunnel syndrome, tarsal tunnel syndrome and anterior interosseous nerve palsy that is entrapment neuropathy. The affected nerve was enhanced in entrapment point. Carpal tunnel syndrome: The enhancement of affected nerve was apparent in 41 of 52 cases (79%). Cubital tunnel syndrome: The enhancement of affected nerve was apparent in 4 of 5 cases (80%). Tarsal tunnel syndrome: The enhancement of affected nerve was apparent in 1 of 1 case. Anterior interosseous nerve palsy: The enhancement of affected nerve was apparent in 3 of 4 cases (75%). The affected nerve was strongly enhanced by Gd-DTPA, indicating the blood-nerve barrier in the affected nerve to be broken and intraneural edema to be produced, e.i., the ability of Gd-DTPA to selectively contrast-enhance a pathologic focus within the peripheral nerve is perhaps its most important clinical applications. (author).
Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P
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 the majority of cases receiving >42 total grams (>4 weeks) of therapy (31 out of 40). In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0-50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 total grams (>4 weeks) of metronidazole compared to those patients receiving ≤ 42 total grams (17.9% vs 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is exceedingly rare in patients who receive ≤ 42 total grams of metronidazole. Patients who receive larger total doses may be at higher risk of peripheral neuropathy but most patients have resolution of symptoms after discontinuing therapy. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 grams of the drug (≤4 weeks). Copyright © 2017. Published by Elsevier B.V.
Full Text Available Objectives: This study aimed to evaluate the evidence available in the literature for the safety and efficacy of Dioscoreae Rhizoma (DR for the treatment of peripheral neuropathy. Methods: Literature searches were performed in MEDLINE and three Korean medical databases up to April 2013. All studies evaluating the effects on peripheral neuropathy or the safety of DR monopreparations were considered. Results: Three studies - DR extract per os (po on diabetic neuropathy in mice, DR extract injection on the peripheral sciatic nerve after crush injury in rats and DR extract injection to patients with peripheral facial paralysis proved that DR treatments were effective for the treatment of nerve injuries. Conclusions: In conclusion, we found the DR has a strong positive potential for the treatment of peripheral neuropathy, but studies addressing direct factors related to the nerve still remain insufficient.
Singh, Kunwarpal; Gupta, Kamlesh; Kaur, Sukhdeep
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 mm2) 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 diabetic patients with no signs of peripheral neuropathy had a larger mean cross sectional area (14.40 +/- 1.72 mm2) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/- 1.01 mm2 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.
Full Text Available Aim of the study: 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. Material and methods: 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. Results: The mean cross sectional area (22.63 +/– 2.66 mm2 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 mm2 and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm than healthy non-diabetic subjects (12.42 +/– 1.01 mm2 and 0.30 mm respectively. Conclusion: 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.
Kamal Kishore Pandita
Full Text Available Churg-Strauss syndrome (CSS is a rare cause of vasculitic neuropathy. Although rare and potentially fatal, Churg-Strauss syndrome (CSS is easily diagnosable and treatable. The presence of bronchial asthma with peripheral neuropathy in a patient alerts a physician to this diagnosis. This is vividly illustrated by the presented two cases who had neuropathy associated with bronchial asthma, eosinophilia, sinusitis, and positive perinuclear antineutrophil cytoplasmic antibodies (p-ANCA test, which improved with administration of steroids.
Farmer, Kevin L.; Li, Chengyuan
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that is associated with axonal atrophy, demyelination, blunted regenerative potential, and loss of peripheral nerve fibers. The development and progression of DPN is due in large part to hyperglycemia but is also affected by insulin deficiency and dyslipidemia. Although numerous biochemical mechanisms contribute to DPN, increased oxidative/nitrosative stress and mitochondrial dysfunction seem intimately associated with nerve dysfunction and diminished regenerative capacity. Despite advances in understanding the etiology of DPN, few approved therapies exist for the pharmacological management of painful or insensate DPN. Therefore, identifying novel therapeutic strategies remains paramount. Because DPN does not develop with either temporal or biochemical uniformity, its therapeutic management may benefit from a multifaceted approach that inhibits pathogenic mechanisms, manages inflammation, and increases cytoprotective responses. Finally, exercise has long been recognized as a part of the therapeutic management of diabetes, and exercise can delay and/or prevent the development of painful DPN. This review presents an overview of existing therapies that target both causal and symptomatic features of DPN and discusses the role of up-regulating cytoprotective pathways via modulating molecular chaperones. Overall, it may be unrealistic to expect that a single pharmacologic entity will suffice to ameliorate the multiple symptoms of human DPN. Thus, combinatorial therapies that target causal mechanisms and enhance endogenous reparative capacity may enhance nerve function and improve regeneration in DPN if they converge to decrease oxidative stress, improve mitochondrial bioenergetics, and increase response to trophic factors. PMID:22885705
Yoganathan, Sangeetha; Bagga, Arvind; Gulati, Sheffali; Toteja, G S; Hari, Pankaj; Sinha, Aditi; Pandey, Ravindra Mohan; Irshad, Mohammad
The aim of this study was to determine the prevalence and predictors of peripheral neuropathy in non-diabetic children with chronic kidney disease (CKD). Fifty-one consecutive normally nourished children, aged 3-18 years, with CKD stage IV and V of non-diabetic etiology were enrolled from May to December 2012. Nerve conduction studies were performed in fifty children. Blood samples were analyzed for the biochemical parameters, trace elements and micronutrients. The prevalence of peripheral neuropathy in our cohort was 52% (95% CI 37.65, 66.34). The majority (80.8%) had axonal neuropathy while 11.5% had demyelinating neuropathy. Isolated motor neuropathy was identified in 92.3% and sensorimotor neuropathy 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 with the aim of optimizing medical care. This article is protected by copyright. All rights reserved. © 2017 Wiley Periodicals, Inc.
Navis, Allison; Jiao, Jocelyn; George, Mary Catherine; Simpson, David; Robinson-Papp, Jessica
Peripheral neuropathy (PN) is a common complication of HIV. There is increasing awareness that some forms of PN, particularly small-fiber neuropathies, can be associated with chronic widespread pain syndromes. Given the high prevalence of both PN and chronic pain in HIV, we sought to determine whether patients with a diagnosis of HIV-PN were more likely to experience other chronic pain syndromes. Data were obtained from the Clinical Data Warehouse maintained by our institution. All HIV-infected patients receiving standard of care antiretroviral therapy in our institution's primary care HIV clinic (N = 638) were included. Diagnoses of HIV-PN and other chronic pain disorders were established based on clinician-assigned ICD-9/10 codes. Sixty-eight patients (11%) had a diagnosis of HIV-PN. Patients with HIV-PN were more than twice as likely to have other chronic pain disorders (66% vs 32%, χ 2 = 30.3, P < 0.001). Patients with HIV-PN were also older and more likely to have substance use and psychiatric disorders; however, the association of HIV-PN with other chronic pain disorders persisted after adjusting for relevant confounders (χ 2 (5) = 81.38, P < 0.001). Patients with HIV-PN commonly experience other chronic pain disorders. Clinicians managing HIV-PN should seek a broad understanding of patients' pain experience as this may alter management strategies. Researchers studying HIV-PN should consider how the presence of other pain disorders might affect outcomes.
Kluding, Patricia M; Pasnoor, Mamatha; Singh, Rupali; D'Silva, Linda J; Yoo, Min; Billinger, Sandra A; LeMaster, Joseph W; Dimachkie, Mazen M; Herbelin, Laura; Wright, Douglas E
.... This was a single-group preliminary study. The setting was an academic medical center. Participants were 18 people who were sedentary and had type 2 diabetes and peripheral neuropathy (mean age=58.1 years, SD=5...
Nybo, M; Poulsen, M K; Grauslund, J
Osteoprotegerin (OPG) has been linked to different diabetes complications, including cardiovascular disease, and new findings have indicated a specific role in diabetic peripheral neuropathy, but the exact mechanism is unknown. To investigate a possible association between OPG and diabetic...
Full Text Available Uwe Wollina Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, Dresden, Germany Abstract: Polycythemia vera is a rare myeloproliferative disease. Cutaneous symptoms are uncommon. We report about a 72-year-old female patient with JAK2V617F-positive polycythemia who developed peripheral sensorimotor axonal neuropathy and erythromelalgia. Possible causes and treatment are discussed. Keywords: bone marrow diseases, myeloproliferative diseases, JAK2 mutations, burning sensations, peripheral neuropathy
Hong-xia Xue; Wen-yi Fu; Hua-dong Cui; Li-li Yang; Ning Zhang; Li-juan Zhao
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 tha...
Hamity, Marta V; White, Stephanie R; Walder, Roxanne Y; Schmidt, Mark S; Brenner, Charles; Hammond, Donna L
Injury to sensory afferents may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a third form of vitamin B3 and precursor of NAD, diminishes tactile hypersensitivity and place escape-avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy. Female Sprague-Dawley rats received 3 intravenous injections of 6.6 mg/kg paclitaxel over 5 days. Daily oral administration of 200 mg/kg NR beginning 7 days before paclitaxel treatment and continuing for another 24 days prevented the development of tactile hypersensitivity and blunted place escape-avoidance behaviors. These effects were sustained after a 2-week washout period. This dose of NR increased blood levels of NAD by 50%, did not interfere with the myelosuppressive effects of paclitaxel, and did not produce adverse locomotor effects. Treatment with 200 mg/kg NR for 3 weeks after paclitaxel reversed the well-established tactile hypersensitivity in a subset of rats and blunted escape-avoidance behaviors. Pretreatment with 100 mg/kg oral acetyl-L-carnitine (ALCAR) did not prevent paclitaxel-induced tactile hypersensitivity or blunt escape-avoidance behaviors. ALCAR by itself produced tactile hypersensitivity. These findings suggest that agents that increase NAD, a critical cofactor for mitochondrial oxidative phosphorylation systems and cellular redox systems involved with fuel utilization and energy metabolism, represent a novel therapeutic approach for relief of chemotherapy-induced peripheral neuropathies. Because NR is a vitamin B3 precursor of NAD and a nutritional supplement, clinical tests of this hypothesis may be accelerated.
Kambiz, S.; Neck, J.W. van; Cosgun, S.G.; Velzen, M.H. van; Janssen, J.A.M.; Avazverdi, N.; Hovius, S.E.; Walbeehm, E.T.
The skin's rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to
Gupta, Harsh V; Lee, Ricky W; Raina, Sunil K; Behrle, Brian L; Hinduja, Archana; Mittal, Manoj K
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.
Full Text Available A 32-year-old man experienced double vision around January, 2010, followed by weakness of his left upper and lower extremities. Articulation disorders and loss of hearing in his left ear developed, and he was admitted to our hospital on February 14, 2010. Physical examination was normal, and neurological examination showed clear consciousness with no impairment of cognitive function, but with articulation disorders. Olfactory sensation was reduced. Left ptosis and left gaze palsy, complete left facial palsy, perceptive deafness of the left ear, and muscle weakness of the left trapezius muscle were observed. Paresis in the left upper and lower extremities was graded 4/5 through manual muscle testing. Sensory system evaluation revealed complete left-side palsy, including the face. Deep tendon reflexes were slightly diminished equally on both sides; no pathologic reflex was seen. No abnormality of the brain parenchyma, cerebral nerves or cervicothoracolumbar region was found on brain magnetic resonance imaging. On electroencephalogram, alpha waves in the main frequency band of 8 to 9 Hz were recorded, indicating normal findings. Brain single photon emission computed tomography (SPECT scan showed reduced blood flow in the right inner frontal lobe and both occipital lobes. Nerve biopsy (left sural nerve showed reduction of nerve density by 30%, with demyelination. The patient also showed manifestations of multiple cranial nerve disorder, i.e., of the trigeminal nerve, glossopharyngeal nerve, vagus nerve, and hypoglossal nerve. Whole-body examination was negative. Finally, based on ischemic brain SPECT images, spinal fluid findings and nerve biopsy results, peripheral neuropathy accompanied with multiple cranial nerve palsy was diagnosed.
Full Text Available A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively, but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively. The modified method required less surgical skill than the spinal nerve ligation model.
Dias, Q.M.; Rossaneis, A.C.; Fais, R.S.; Prado, W.A. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)
A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively) similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively), but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively). The modified method required less surgical skill than the spinal nerve ligation model.
Bell, David S H
Chronic metformin use results in vitamin B12 deficiency in 30% of patients. Exhaustion of vitamin B12 stores usually occurs after twelve to fifteen years of absolute vitamin B12 deficiency. Metformin has been available in the United States for approximately fifteen years. Vitamin B12 deficiency, which may present without anemia and as a peripheral neuropathy, is often misdiagnosed as diabetic neuropathy, although the clinical findings are usually different. Failure to diagnose the cause of the neuropathy will result in progression of central and/or peripheral neuronal damage which can be arrested but not reversed with vitamin B12 replacement. To my knowledge, this is the first report of metformin-induced vitamin B12 deficiency causing neuropathy.
Ferreira, Jean P; Sartor, Cristina D; Leal, Ângela M O; Sacco, Isabel C N; Sato, Tatiana O; Ribeiro, Ivana L; Soares, Alice S; Cunha, Jonathan E; Salvini, Tania F
Skeletal muscle strength is poorly described and understood in diabetic participants with diabetic peripheral neuropathy. This study aimed to investigate the extensor and flexor torque of the knee and ankle during concentric, eccentric, and isometric contractions in men with diabetes mellitus type 2 with and without diabetic peripheral neuropathy. Three groups of adult men (n=92), similar in age, body mass index, and testosterone levels, were analyzed: 33 non-diabetic controls, 31 with type 2 diabetes mellitus, and 28 with diabetic peripheral neuropathy. The peak torques in the concentric, eccentric, and isometric contractions were evaluated using an isokinetic dynamometer during knee and ankle flexion and extension. Individuals with diabetes and diabetic peripheral neuropathy presented similar low concentric and isometric knee and ankle torques that were also lower than the controls. However, the eccentric torque was similar among the groups, the contractions, and the joints. Regardless of the presence of peripheral neuropathy, differences in skeletal muscle function were found. The muscle involvement does not follow the same pattern of sensorial losses, since there are no distal-to-proximal impairments. Both knee and ankle were affected, but the effect sizes of the concentric and isometric torques were found to be greater in the participants' knees than in their ankles. The eccentric function did not reveal differences between the healthy control group and the two diabetic groups, raising questions about the involvement of the passive muscle components. Copyright © 2017 Elsevier Ltd. All rights reserved.
Millán-Guerrero, Rebeca O; Vásquez, Clemente; Isaís-Millán, Sara; Trujillo-Hernández, Benjamín; Caballero-Hoyos, Ramiro
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.
Misra, Stuti L.; Dipika V Patel; McGhee, Charles N. J.; Monika Pradhan; Dean Kilfoyle; Braatvedt, Geoffrey D; Craig, Jennifer P.
Purpose. To compare tear film metrics in patients with type 1 diabetes mellitus (DM) and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. Methods. Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy ...
Full Text Available Purpose: In order to estimate clinical effects of acupotomy and venesection in a patient with peripheral neuropathy and upper limb lymphedema following breast cancer surgery. Methods: From 17th August, 2009 to 29th August 2009, 1 female patient with peripheral neuropathy and upper limb lymphedema following breast cancer surgery was treated with general oriental medicine therapy(acupuncture, moxibustion, cupping, physical therapy, herbal medication and acupotomy with venesection. Results: The patient's chief complaints- Lt hand numbness, Lt arm edema, Lt. wrist flexion limitation - were notably improved. Conclusions : This study demonstrates that oriental medical treatment with acupotomy and venesection therapy has significant effect in improving symptoms of peripheral neuropathy and upper limb lymphedema following breast cancer surgery, as though we had not wide experience in this treatment, more research is needed.
Taylor, Sean W; Laughlin, Ruple S; Kumar, Neeraj; Goodman, Brent; Klein, Christopher J; Dyck, Peter J; Dyck, P James B
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 (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.
Samuel Oliveira de Afonseca
Full Text Available CONTEXT AND OBJECTIVEOxaliplatin is one of the chemotherapy regimens most used for treating colorectal cancer. One of the main limitations to its use is induction of peripheral neuropathy. Previous studies have shown that vitamin E can reduce the incidence of peripheral neuropathy by 50%. This study aimed to assess the effectiveness of vitamin E for prevention of oxaliplatin-induced peripheral neuropathy.DESIGN AND SETTINGProspective, phase II, randomized pilot study developed at a university hospital in the Greater ABC region.METHODSPatients were randomized five days before starting oxaliplatin treatment, to receive either vitamin E or placebo until the end of the chemotherapy regimen. The outcome was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE, version 3, and specific gradation scales for oxaliplatin-induced peripheral neuropathy. Patients with colorectal and gastric cancer who had been scheduled to receive oxaliplatin-based chemotherapy were included. Both groups received calcium and magnesium supplementation before and after oxaliplatin infusions.RESULTSEighteen patients were randomized to the vitamin E group and 16 to the placebo group. Cumulative incidence of 83% with peripheral neuropathy grades 1/2 was observed in the vitamin E group, versus 68% in the placebo group (P = 0.45. A trend towards more diarrhea was observed among patients who received vitamin E (55.6% vs. 18.8%; P = 0.06. There were no other significant differences in toxicity between the groups.CONCLUSIONSNo significant decrease in the incidence of acute oxaliplatin-induced peripheral neuropathy was demonstrated through vitamin E use.CLINICAL TRIAL REGISTRATIONNCT01523574.
Bracewell, N; Game, F; Jeffcoate, W; Scammell, B E
Current National Institute for Health and Clinical Excellence guidelines state that patients with diabetes should have annual examination of their feet to exclude signs of sensory impairment. The VibraTip is a new disposable device producing a vibratory stimulus, which has been developed in order to screen for peripheral sensory neuropathy in diabetes. This study was designed to evaluate the device by assessing intra-rater reliability and comparing the ability of the VibraTip to detect or exclude peripheral sensory neuropathy with other bedside methods. One hundred and forty-one patients with diabetes (Type 1 or Type 2) were examined for diabetic peripheral sensory neuropathy using a Neurothesiometer, 10-g monofilament, a 128-Hz tuning fork, a Neurotip™ and a VibraTip. The failure to perceive the Neurosthesiometer stimulus at ≥ 25 V in either foot was considered the reference method for the presence of peripheral sensory neuropathy. Receiver operating characteristic curves were produced for each device and the sensitivity, specificity, predictive values and likelihood ratios for the diagnosis of peripheral sensory neuropathy were calculated. Repeat testing with the VibraTip was performed in 18 patients and intra-rater reliability assessed using Cronbach alpha. Analysis of the area under the receiver operating characteristic curves showed that the 10-g monofilament was significantly better than the 128-Hz tuning fork (P = 0.0056) and the Neurotip (P = 0.0022), but was no different from the VibraTip (P = 0.3214). The alpha coefficient for the VibraTip was calculated to be 0.882, indicating good reliability. The VibraTip is a device comparable with the 10-g monofilament and therefore could be considered a useful tool for screening for peripheral sensory neuropathy in diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.
Song, Tieying; Zhao, Jianhui; Ma, Xiaojing; Zhang, Zaiwang; Jiang, Bo; Yang, Yunliang
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.
S.I. van Nes (Sonja)
textabstractIn this thesis, the outline and the results of the fi rst part of the Peripheral Neuropathy outcome measures Standardisation (PeriNomS) study are described. The PeriNomS study aims to improve and standardise the assessment of patients with immune-mediated neuropathies. These disorders
Eckhoff, L.; Knoop, A.; Jensen, M. B.
BACKGROUND: This study evaluates persistence and severity of docetaxel-induced neuropathy (peripheral neuropathy (PN)) and impact on health related quality of life in survivors from early-stage breast cancer. METHODS: One thousand and thirty-one patients with early-stage breast cancer, who received...... at least one cycle of docetaxel and provided information on PN during treatment, completed questionnaires on PN as an outcome (Common Toxicity Criteria (CTC) scores, European Organisation for Research and Treatment of Cancer Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC CIPN20) and EORTC Quality...
Melemedjian Ohannes K
Full Text Available Abstract Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG, which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.
Jin, Jiewen; Wang, Weimin; Gu, Tianwei; Chen, Wei; Lu, Jing; Bi, Yan; Zhu, Dalong
Purpose Diabetic peripheral neuropathies are the common chronic complications of diabetes, but the diagnosis is insensitive by physical examination in busy outpatients. Here we evaluated the performance of SUDOSCAN in screening diabetic peripheral neuropathies in Chinese type 2 diabetic patients. Methods The study enrolled 180 patients for annually screening. All patients underwent neurological symptoms assessment, clinical examination, nerve conduction studies and cardiovascular autonomic reflex tests. SUDOSCAN was tested and evaluated with electrochemical skin conductance in hands and feet, asymmetry ratio in hands and feet and predicted cardiac neuropathy. Results Patients enrolled had an average age of 56.1 years, 9.8 years of diabetic duration. Patients with diabetic sensorimotor polyneuropathy showed significantly lower electrochemical skin conductance in feet and higher asymmetry ratio in feet compared with those without. Sensitivity and specificity of asymmetry ratio in feet for diagnosing diabetic sensorimotor polyneuropathy were 88.2% and 46.9% and area under ROC curve was 0.713. Patients with cardiovascular autonomic neuropathy showed significantly lower electrochemical skin conductance in hands and feet, and higher asymmetry ratio in feet and predicted cardiac neuropathy compared with those without. Sensitivity and specificity of electrochemical skin conductance in feet in diagnosing cardiovascular autonomic neuropathy were 85.6% and 76.1% with an area under ROC curve of 0.859. Conclusions SUDOSCAN is a sensitive test to detect diabetic peripheral neuropathy in China and could be an effective screening tool in in busy outpatients and primary health care. © Georg Thieme Verlag KG Stuttgart · New York.
Hedges, T R; Hirano, M; Tucker, K; Caballero, B
During 1992 and 1993 an epidemic of optic and peripheral neuropathy affected over 50,000 Cubans. This occurred in the unique setting of a communist country which had a widespread health care network and wherein sudden changes in the economy affected most of the population. Although nutritional factors appeared to play a key role in the pathogenesis of the epidemic neuropathy, viral, toxic, and genetic factors were investigated by Cuban and North American scientists. The authors, representing different disciplines and different groups that visited Cuba during the epidemic, review and reflect on the clinical and laboratory findings which became available through their own experience and through reviewing the literature. The recent Cuban epidemic is compared to similar outbreaks of optic and peripheral neuropathy which have occurred in the past.
Walsh, Maie; Bell, Katrina M; Chong, Belinda; Creed, Emma; Brett, Gemma R; Pope, Kate; Thorne, Natalie P; Sadedin, Simon; Georgeson, Peter; Phelan, Dean G; Day, Timothy; Taylor, Jessica A; Sexton, Adrienne; Lockhart, Paul J; Kiers, Lynette; Fahey, Michael; Macciocca, Ivan; Gaff, Clara L; Oshlack, Alicia; Yiu, Eppie M; James, Paul A; Stark, Zornitza; Ryan, Monique M
To explore the diagnostic utility and cost effectiveness of whole exome sequencing (WES) in a cohort of individuals with peripheral neuropathy. Singleton WES was performed in individuals recruited though one pediatric and one adult tertiary center between February 2014 and December 2015. Initial analysis was restricted to a virtual panel of 55 genes associated with peripheral neuropathies. Patients with uninformative results underwent expanded analysis of the WES data. Data on the cost of prior investigations and assessments performed for diagnostic purposes in each patient was collected. Fifty patients with a peripheral neuropathy were recruited (median age 18 years; range 2-68 years). The median time from initial presentation to study enrollment was 6 years 9 months (range 2 months-62 years), and the average cost of prior investigations and assessments for diagnostic purposes AU$4013 per patient. Eleven individuals received a diagnosis from the virtual panel. Eight individuals received a diagnosis following expanded analysis of the WES data, increasing the overall diagnostic yield to 38%. Two additional individuals were diagnosed with pathogenic copy number variants through SNP microarray. This study provides evidence that WES has a high diagnostic utility and is cost effective in patients with a peripheral neuropathy. Expanded analysis of WES data significantly improves the diagnostic yield in patients in whom a diagnosis is not found on the initial targeted analysis. This is primarily due to diagnosis of conditions caused by newly discovered genes and the resolution of complex and atypical phenotypes.
Yorek, Mark A.
This article reviews the impact of diabetes and its treatment on vascular function with a focus on the reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve. Another focus is the relationship between the dysregulation of neurovascular function and diabetic peripheral neuropathy. Diabetic peripheral neuropathy is a debilitating disorder that occurs in more than 50 percent of patients with diabetes. The etiology involves metabolic, vascular, and immunologic pathways besides neurohormonal growth factor deficiency and extracellular matrix remodeling. In the light of this complex etiology, an effective treatment for diabetic peripheral neuropathy has not yet been identified. Current opinion postulates that any effective treatment for diabetic peripheral neuropathy will require a combination of life style and therapeutic interventions. However, a more comprehensive understanding of the factors contributing to neurovascular and neural dysfunction in diabetes is needed before such a treatment strategy can be developed. After reading this review, the reader should have gained insight into the complex regulation of vascular function and blood flow to the sciatic nerve, and the impact of diabetes on numerous elements of vascular reactivity of epineurial arterioles of the sciatic nerve. PMID:26676659
Lefrandt, JD; Hoeven, JH; Roon, AM; Smit, AJ; Hoogenberg, K
Aims/hypothesis. A loss of sympathetic function could lead to changes in capillary fluid filtration in diabetic patients. We investigated whether a decreased sympathetically mediated vasomotion in the skin in diabetic patients with peripheral neuropathy is associated with an abnormal capillary
Xu, Wei-Ru; Hua, Bao-Jin; Hou, Wei; Bao, Yan-Ju
To seek the effective treatment for peripheral neuropathy induced by chemotherapeutic drugs. Sixty-four cases of peripheral neuropathy induced by Paclitaxel or Oxaliplatin were randomly divided into an acupuncture group and a medication group, 32 cases in each group. The acupuncture group was treated with therapeutic principle of dredging meridians and collaterals, tonifying qi and eliminating blood stasis, supplementing liver and kidney, nourishing blood and tendon. Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36), Qihai (CV 6) and Quchi (LI 11) etc. were selected. The medication group was treated with intramuscular injection of Cobamamide. The neurotoxicity of two groups was compared with questionnaire of peripheral neuropathy induced by chemotherapeutic drugs before and after treatment. The total effective rate for sensory nerve disorder of acupuncture group was 66.7% (20/30), which was superior to that of 40.0% (12/30) in medication group (P Cobamamide for treatment of peripheral neuropathy induced by chemotherapeutic drugs, especially for moderate and severe sensory nerve disorder induced by paclitaxel.
Although the life expectancy of people living with HIV/AIDS (PLWH) has increased in the past years, they could experience secondary illness such as peripheral neuropathy (PN). Therefore, they need to adapt to chronic disablement which could affect their quality of life (QoL). The research that informed this article aimed at ...
S.L. Corthals (Sophie); R. Kuiper (Ruud); D.C. Johnson (David); P. Sonneveld (Pieter); R. Hajek (Roman); B. van der Holt (Bronno); F. Magrangeas (Florence); H. Goldschmidt (Hartmut); G. Morgan (Gareth); H. Avet-Loiseau
textabstractBortezomib induced peripheral neuropathy is a dose-limiting side effect and a major concern in the treatment of multiple myeloma. To identify genetic risk factors associated with the development of this side effect in bortezomib treated multiple myeloma patients, a pharmacogenetic
Sundar Prakash S, Krishnakumar, Chandra Prabha
Full Text Available Objective: Peripheral neuropathy and Peripheral Vascular Disease are the risk factors for the development of diabetic foot. The aim of this study was to evaluate differences and predictors of outcome parameters in patients with diabetic foot by stratifying these subjects according to the severity of these risk factors. Materials and methods: This is a prospective study conducted in 70 patients in the age group of 30-90 years diagnosed as Type II Diabetes with foot ulcers. After detailed clinical examination the following tests were conducted in all the patients: Complete blood count (CBC, Haemoglobin (Hb, Random Blood Sugar (RBS, Erythrocyte Sedimentation rate (ESR, Chest X-ray(CXR, Electrocardiography (ECG, foot X-ray, pus culture, Neuropathy testing by Semmes Weinstein Monofilament Test and Vibration Perception Threshold and Peripheral vascularity assessment by Duplex Doppler. Then grading of the ulcers was done using Wagner’s Grade. The outcome of the patients was assessed by recording the healing time, mode of surgery and amputation rates of the patients. Results: A total of 70 patients with diabetic foot were consecutively included into the study (65.7% male, age (31% in 51-60 years, mean diabetes duration (5.2 years, Ulcer Grade (37% in Grade IV, Foot lesions (45.7% in toe, Blood sugar levels (64% in 300-400 mg/dl, Neuropathy (84%, Peripheral vascular disease (67%, major amputation (7% and mortality (1.4%. Conclusion: All diabetic patients should undergo testing for neuropathy and peripheral vascular disease apart from doing other tests.
Erika Hissong, M.D.
Full Text Available Peripheral neuropathy, white matter abnormalities, and cardiomyopathy are associated findings with merosin-deficient congenital muscular dystrophy. Although characterization of the neuropathy with nerve conduction studies has been well documented, limited research has been able to correlate histopathology with nerve biopsy in humans. Our understanding of the mechanism, described as a demyelinating neuropathy, is mainly derived from mouse model studies. We report a 23-year-old male who succumbed to respiratory failure and ultimately cardiac arrhythmia in the setting of an uncharacterized end stage progressive muscular disease complicated by cardiomyopathy and severe scoliosis. Autopsy revealed extensive muscular atrophy and replacement by fibroadipose tissue throughout the skeletal muscle and myocardium. Immunohistochemical analysis of the muscle biopsy showed a complete loss of merosin. Thus, the cause for both his muscular disease and demyelinating neuropathy was established with the diagnosis of merosin-deficient muscular dystrophy. Nerve biopsy obtained from the cauda equina showed clear evidence of segmental demyelination and remyelination, providing a better understanding of the proximal peripheral nerve histopathological changes in this disease entity.
Stuti L. Misra
Full Text Available Purpose. To compare tear film metrics in patients with type 1 diabetes mellitus (DM and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. Methods. Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment. Results. Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups (P=0.12 and P=0.33, resp.. Tear lipid thickness (P=0.02, stability (P<0.0001, and quantity (P=0.01 were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group (P<0.001 and tear film stability was inversely associated with total neuropathy score (r=-0.29, P=0.03. Conclusion. The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy.
Barreira, A A; Marques Júnior, W
Studies on peripheral neuropathies by investigators residing in the State of São Paulo, Brazil, and published since the 1930 and 1940 decades until 1985 were revised in the present survey. Investigations in the area were greatly encouraged by the appearance of the journal Arquivos de Neuro-Psiquiatria(São Paulo). Oswaldo Freitas Julião may be considered the author who began these studies in the State and his most important contributions were related to leprosy and to Andrade disease, although he also published papers on other types of peripheral neuropathies. Horacio Martins Canelas also made a very important contribution to the study of different neuropathies, especially those due to vitamin B12 deficiency. A series of papers on neuropathies published by neurologists residing in the State is summarized. We also present a catalogue of the major university centers where groups of neurologists preferentially devote their time to the study of neuromuscular disease in São Paulo and a selected bibliography about neuropathies by investigators from this State.
Misra, Stuti L; Patel, Dipika V; McGhee, Charles N J; Pradhan, Monika; Kilfoyle, Dean; Braatvedt, Geoffrey D; Craig, Jennifer P
To compare tear film metrics in patients with type 1 diabetes mellitus (DM) and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment. Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups (P = 0.12 and P = 0.33, resp.). Tear lipid thickness (P = 0.02), stability (P < 0.0001), and quantity (P = 0.01) were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group (P < 0.001) and tear film stability was inversely associated with total neuropathy score (r = -0.29, P = 0.03). The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy.
Vinik, A I; Casellini, C; Névoret, M-L
Here we review some seldom-discussed presentations of diabetic neuropathy, including large fiber dysfunction and peripheral autonomic dysfunction, emphasizing the impact of sympathetic/parasympathetic imbalance. Diabetic neuropathy is the most common complication of diabetes and contributes additional risks in the aging adult. Loss of sensory perception, loss of muscle strength, and ataxia or incoordination lead to a risk of falling that is 17-fold greater in the older diabetic compared to their young nondiabetic counterparts. A fall is accompanied by lacerations, tears, fractures, and worst of all, traumatic brain injury, from which more than 60% do not recover. Autonomic neuropathy has been hailed as the "Prophet of Doom" for good reason. It is conducive to increased risk of myocardial infarction and sudden death. An imbalance in the autonomic nervous system occurs early in the evolution of diabetes, at a stage when active intervention can abrogate the otherwise relentless progression. In addition to hypotension, many newly recognized syndromes can be attributed to cardiac autonomic neuropathy such as orthostatic tachycardia and bradycardia. Ultimately, this constellation of features of neuropathy conspire to impede activities of daily living, especially in the patient with pain, anxiety, depression, and sleep disorders. The resulting reduction in quality of life may worsen prognosis and should be routinely evaluated and addressed. Early neuropathy detection can only be achieved by assessment of both large and small- nerve fibers. New noninvasive sudomotor function technologies may play an increasing role in identifying early peripheral and autonomic neuropathy, allowing rapid intervention and potentially reversal of small-fiber loss. © 2016 Elsevier Inc. All rights reserved.
Cg, Shashi Kumar; Maiya, Arun G; Hande, H Manjunath; Vidyasagar, Sudha; Rao, Karthik; Rajagopal, K V
Diabetic peripheral neuropathy (DPN) accounts for most common complications of T2DM. Painful DPN is associated with functional limitation & poor quality of life. Therefore, objective of the study is to find the effect of low level laser therapy on painful diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) Materials & methods: The study design is pre-post observational design. After obtaining ethical clearance and informed consent, 19 T2DM subjects were screened and confirmed for peripheral neuropathy in an outpatient setting with biochemical parameter, pain scale and Michigan Neuropathy Screening Instrument (MNSI). Low Level Laser therapy was irradiated through scanning mode with dosage of 3.1J/cm(2) on the plantar and dorsum of the foot and 3.4j/cm(2) with contact method for 10days and all subjects were reassessed at the end of the 10 day. Descriptive statistics and paired' test was used to analyze the pre-post finding within the group. Level of significance was set at pneuropathy.
Stavniichuk, Roman; Shevalye, Hanna; Lupachyk, Sergey; Obrosov, Alexander; Groves, John T; Obrosova, Irina G; Yorek, Mark A
Peroxynitrite, a product of the reaction of superoxide with nitric oxide, causes oxidative stress with concomitant inactivation of enzymes, poly(ADP-ribosylation), mitochondrial dysfunction and impaired stress signalling, as well as protein nitration. In this study, we sought to determine the effect of preventing protein nitration or increasing peroxynitrite decomposition on diabetic neuropathy in mice after an extended period of untreated diabetes. C57Bl6/J male control and diabetic mice were treated with the peroxynitrite decomposition catalyst Fe(III) tetramesitylporphyrin octasulfonate (FeTMPS, 10 mg/kg/day) or protein nitration inhibitor (-)-epicatechin gallate (20 mg/kg/day) for 4 weeks, after an initial 28 weeks of hyperglycaemia. Untreated diabetic mice developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia and loss of intraepidermal nerve fibres. Both FeTMPS and epicatechin gallate partially corrected sensory nerve conduction slowing and small sensory nerve fibre dysfunction without alleviation of hyperglycaemia. Correction of motor nerve conduction deficit and increase in intraepidermal nerve fibre density were found with FeTMPS treatment only. Peroxynitrite injury and protein nitration are implicated in the development of diabetic peripheral neuropathy. The findings indicate that both structural and functional changes of chronic diabetic peripheral neuropathy can be reversed and provide rationale for the development of a new generation of antioxidants and peroxynitrite decomposition catalysts for treatment of diabetic peripheral neuropathy. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.
Kiziltan, Meral E; Akalin, M Ali; Sahin, Rahsan; Uluduz, Derya
The aim of this study is to evaluate the peripheral nerves in diabetes mellitus with or without peripheral facial paralysis (PFP). A total of 49 diabetic patients with PFP within the last year (23 females, mean age 60.3 +/- 9.3), and 83 diabetic patients without PFP (41 females, mean age 59.5 +/- 9.9) were enrolled. The neurological examination, eye-blinking response, needle EMG and electrophysiological parameters of peripheral nerves were evaluated. The neuropathic pain, other positive and negative sensory symptoms were statistically more frequent in controls than the PFP group, while no difference was noted in total neuropathy score. Sural sensorial nerve action potential amplitudes were same in both groups, but median nerve amplitudes were significantly lower in the PFP group. It is suggested that PFP is not a part of multifocal neuropathy in diabetes mellitus. However, at least some parts of the nerve conduction studies were involved, focal neuropathies were more frequent while sensory neuropathies with small nerve fiber involvement were less frequent in diabetes patients with PFP.
Jønsson, V; Schrøder, H D; Trojaborg, W
-protein and complement C3b to myelin-associated glycoproteins (MAG). In 12 cases with axonal neuropathy, binding of IgG to the connective tissue of the peri- and endoneurium was found in 50% of cases, IgM in five cases, and IgD in one case. None of the patients had central nervous system (CNS) symptoms. The clinical......A study of 17 patients with autoimmune axonal or demyelinating peripheral neuropathy in combination with M-component is described. The M-component was associated with MGUS (monoclonal gammopathy of undetermined significance) in 12 patients, CLL in one patient, Waldenström's disease in one patient...
Tariman, Joseph D; Love, Ginger; McCullagh, Emily; Sandifer, Stacey
The novel therapies thalidomide and bortezomib can cause peripheral neuropathy, a challenging adverse event that can affect quality of life and compromise optimal treatment for patients with multiple myeloma. At baseline, patients should be evaluated for signs and symptoms of peripheral neuropathy with a neurotoxicity assessment tool and educated about the symptoms and the importance of reporting them. Signs, symptoms, and the ability to perform activities of daily living should be evaluated regularly so that appropriate interventions can be employed if necessary. Specific management strategies for peripheral neuropathy are based on the grade of severity and on signs and symptoms; strategies include dose and schedule modifications, pharmacologic interventions, nonpharmacologic approaches, and patient education.
Holmboe, Eric S; Wang, Yun; Brass, Lawrence M
At the time of repatriation in 1973, a substantial number of Vietnam prisoners of war (POWs) were diagnosed with upper extremity peripheral neuropathy (UEPN). To assess the long-term functional consequences of UEPN among former Vietnam POWs diagnosed with UEPN at repatriation. Former POWs with an International Classification of Diseases, Eighth Revision, code of peripheral neuropathy identified from a central database registry. Cross-sectional survey. Standardized survey instruments and the SF-12 questionnaire were mailed to all subjects. A subsample of subjects completing the mailed survey was contacted by telephone to complete a semistructured questionnaire on current symptoms and physical limitations attributable to peripheral neuropathy. Seventy-nine percent of POWs diagnosed with peripheral neuropathy at repatriation currently experience some numbness or tingling more than 25 years after repatriation, and 63% currently experience pain in one or both hands. Although the average severity rating for numbness and pain was mild, 23% of the POWs still have moderate to severe pain. Ulnar neuropathy was present in more than 30% of the POWs. SF-12 physical composite scores were substantially lower among this group of POWs compared with an age-matched group from the Medical Outcomes Study. For those POWs diagnosed with UEPN at repatriation, nearly 80% continue to experience symptoms of numbness, tingling, and pain, with nearly 25% reporting a moderate or greater degree of symptoms. The low physical function scores of this cohort are particularly troubling. More research concerning physical symptoms and conditions among former POWs is needed, and this research should also investigate what causes are responsible for the significantly lower physical functional status.
Carlos, Fernando; Espejel, Luis; Novick, Diego; López, Rubén; Flores, Daniel
Painful diabetic peripheral neuropathy affects 40-50% of patients with diabetic neuropathy, leading to impaired quality of life and substantial costs. Duloxetine and pregabalin have evidence-based support, and are formally approved for controlling painful diabetic peripheral neuropathy. We used a 12-week decision model for examining painful diabetic peripheral neuropathy first-line therapy with daily doses of duloxetine 60mg or pregabalin 300mg, under the perspective of the Instituto Venezolano de los Seguros Sociales. We gathered model parameters from published literature and expert´s opinion, focusing on the magnitude of pain relief, the presence of adverse events, the possibility of withdrawal owing to intolerable adverse events or due to lack of efficacy, and the quality-adjusted life years expected in each strategy. We analyzed direct medical costs (which are expressed in Bolívares Fuertes, BsF) comprising drug acquisition besides additional care devoted to treatment of adverse events and poor pain relief. We conducted both deterministic and probabilistic sensitivity analyses. Total expected costs per 1000 patients were BsF 1 046 146 (26%) lower with duloxetine than with pregabalin. Most of these savings (91%) corresponds to the difference in the acquisitions cost of each medication. duloxetine also provided 23 more patients achieving good pain relief and a gain of about two quality-adjusted life years per 1000 treated. Model was robust to plausible changes in main parameters. Duloxetine remained the preferred option in 93.9% of the second-order Monte Carlo simulations. This study suggests duloxetine dominates (i.e., is more effective and lead to gains in quality-adjusted life years), remaining less costly than pregabalin for treatment of painful diabetic peripheral neuropathy.
Ng, Judy King Man; Malotka, Joachim; Kawakami, Naoto; Derfuss, Tobias; Khademi, Mohsen; Olsson, Tomas; Linington, Christopher; Odaka, Masaaki; Tackenberg, Björn; Prüss, Harald; Schwab, Jan M.; Harms, Lutz; Harms, Hendrik; Sommer, Claudia; Rasband, Matthew N.; Eshed-Eisenbach, Yael; Peles, Elior; Hohlfeld, Reinhard; Yuki, Nobuhiro; Dornmair, Klaus
Objectives: We asked whether autoantibodies against neurofascin (NF)186 or NF155, both localized at the nodes of Ranvier, are present in serum of patients with inflammatory neuropathy, and whether NF-specific monoclonal antibodies are pathogenic in vivo. Methods: We cloned human NF155 and NF186, and developed an ELISA and cell-based assay to screen for antibodies to human NF in a total of 434 donors including 294 patients with Guillain-Barré syndrome variants acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy, and chronic inflammatory demyelinating polyneuropathy (CIDP). We characterized reactive samples by isotyping, tissue section staining, and epitope mapping. We also injected NF-specific monoclonal antibodies IV into rats with experimental autoimmune neuritis. Results: We detected autoantibodies to NF by ELISA in 4% of patients with AIDP and CIDP, but not in controls. Most positive samples contained immunoglobulin G (IgG)1, IgG3, or IgG4 antibodies directed to only one isoform of NF. Two patients with CIDP showed particularly high (1:10,000 dilution) NF155-specific reactivity in both assays and stained paranodes. Two other patients with CIDP who benefited from plasma exchange exhibited antibodies to NF155 by ELISA, and upon affinity purification, antibodies to both isoforms were observed by both assays. Anti-NF monoclonal antibodies enhanced and prolonged induced neuritis in rats. Conclusions: Autoantibodies to NF are detected in a very small proportion of patients with AIDP and patients with CIDP, but may nevertheless be pathogenic in these cases. PMID:23100406
Kazemi, Maryam; Moghimbeigi, Abbas; Kiani, Javad; Mahjub, Hossein; Faradmal, Javad
Diabetes is increasing in worldwide prevalence, toward epidemic levels. Diabetic neuropathy, one of the most common complications of diabetes mellitus, is a serious condition that can lead to amputation. This study used a multicategory support vector machine (MSVM) to predict diabetic peripheral neuropathy severity classified into four categories using patients' demographic characteristics and clinical features. In this study, the data were collected at the Diabetes Center of Hamadan in Iran. Patients were enrolled by the convenience sampling method. Six hundred patients were recruited. After obtaining informed consent, a questionnaire collecting general information and a neuropathy disability score (NDS) questionnaire were administered. The NDS was used to classify the severity of the disease. We used MSVM with both one-against-all and one-against-one methods and three kernel functions, radial basis function (RBF), linear, and polynomial, to predict the class of disease with an unbalanced dataset. The synthetic minority class oversampling technique algorithm was used to improve model performance. To compare the performance of the models, the mean of accuracy was used. For predicting diabetic neuropathy, a classifier built from a balanced dataset and the RBF kernel function with a one-against-one strategy predicted the class to which a patient belonged with about 76% accuracy. The results of this study indicate that, in terms of overall classification accuracy, the MSVM model based on a balanced dataset can be useful for predicting the severity of diabetic neuropathy, and it should be further investigated for the prediction of other diseases.
Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer
Loprinzi, Paul D; Hager, Kathy K; Ramulu, Pradeep Y
To determine if physical activity and/or blood glycohemoglobin (HbA1c) are associated with the prevalence of peripheral neuropathy (PN) in a representative population of diabetics. Three hundred thirty-nine diabetic participants (40-85 yrs) taking part in 2003-2004 National Health and Nutrition Examination Survey were studied. Participants were defined as having peripheral neuropathy if examination determined ≥1 insensate area in either foot. Moderate-to-vigorous physical activity (MVPA) was objectively-measured using accelerometry. After adjustments, MVPA was not significantly associated with PN (OR=1.16; 95% CI: 0.48-2.78), nor was HbA1c (OR=0.55; 95% CI: 0.28-1.04). However, there was evidence of statistical interaction (OR=0.24; 95% CI: 0.06-0.87) between MVPA and HbA1c status, showing that diabetics engaging in higher levels of MVPA and having normal HgbA1c levels were less likely to have PN than what would be expected based on the individual effects of MVPA and HbA1c alone. Although MVPA was not directly associated with PN, these findings suggest that proper physical activity, coupled with good glycemic control, is associated with less neuropathy. Future longitudinal studies are required to evaluate whether physical activity and improved glycemic control may help prevent or slow the progression of diabetic end-organ damage, particularly diabetic neuropathy. © 2013.
Pai, Yen-Wei; Lin, Ching-Heng; Lee, I-Te; Chang, Ming-Hong
To investigate the prevalence and risk factors for diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese. A cross-sectional, hospital-based observational study was conducted. We enrolled 2837 adults with type 2 diabetes mellitus. Diabetic peripheral neuropathy with or without pain were diagnosed using 2 validated screening tools, namely the Michigan Neuropathy Screening Instrument and Douleur Neuropathique 4 questionnaire. In our sample, 2233 participants had no neuropathy, 476 had diabetic peripheral neuropathy without pain, and 128 had diabetic peripheral neuropathy with neuropathic pain, representing an overall diabetic peripheral neuropathy prevalence of 21.3%, and the prevalence of neuropathic pain in diabetic peripheral neuropathy was 21.2%. Multivariate analysis revealed that older age (Pdiabetic peripheral neuropathy, whereas older age (Pdiabetic peripheral neuropathy with neuropathic pain. During clinical visits involving biochemical studies, the risk for diabetic peripheral neuropathy with neuropathic pain should be considered for people with older age, elevated glycated haemoglobin, low high-density lipoprotein cholesterol and overt proteinuria, with particular attention given to increased levels of albuminuria while concerning neuropathic pain. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Background: Peripheral nerve damage is a common complication of diabetes mellitus and often presents with a gamut of unpleasant sensations difficult to assess accurately clinically. Objective: To describe the United Kingdom Screening Test (UKST), a simple, accurate and reproducible clinical method for assessing the ...
Quintyne, K I
The authors herein report the case of a 35-year-old woman undergoing adjuvant therapy for node positive breast cancer, who presented with short and rapidly progressive history of bilateral lower limb symptoms of peripheral neuropathy following therapy with paclitaxel. MRI of her neural axis revealed no leptomeningeal enhancement or focal metastatic lesions. Neurophysiological tests favoured toxic sensory axonal polyneuropathy. She remains symptomatic following discontinuation of therapy 20 months ago, and is under review with pain management.
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 B12B12 deficiency as 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.
Chiba, Terumasa; Oka, Yusuke; Kambe, Toshie; Koizumi, Naoya; Abe, Kenji; Kawakami, Kazuyoshi; Utsunomiya, Iku; Taguchi, Kyoji
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.
Areti, Aparna; Komirishetty, Prashanth; Akuthota, Manasaveena; Malik, Rayaz A; Kumar, Ashutosh
Oxaliplatin, an organoplatinum compound, is used in the treatment of colorectal cancer, but its clinical use can be limited due to the development of peripheral neuropathy. Whilst mitochondrial dysfunction has been implicated as a major pathomechanism for oxaliplatin-induced neurotoxicity, the prevention of autophagy may also aggravate neuronal cell death. Melatonin, a well-known mitoprotectant and autophagy inducer, was used to examine its neuroprotective role in oxaliplatin-induced peripheral neuropathy (OIPN). Melatonin prevented the loss of mitochondrial membrane potential (Ψm) and promoted neuritogenesis in oxaliplatin-challenged neuro-2a cells. It did not interfere with the cytotoxic activity of oxaliplatin in human colon cancer cell line, HT-29. Melatonin treatment significantly alleviated oxaliplatin-induced pain behavior and neuropathic deficits in rats. It also ameliorated nitro-oxidative stress mediated by oxaliplatin, thus prevented nitrosylation of proteins and loss of antioxidant enzymes, and therefore, it improved mitochondrial electron transport chain function and maintained cellular bioenergetics by improving the ATP levels. The protective effects of melatonin were attributed to preventing oxaliplatin-induced neuronal apoptosis by increasing the autophagy pathway (via LC3A/3B) in peripheral nerves and dorsal root ganglion (DRG). Hence, it preserved the epidermal nerve fiber density in oxaliplatin-induced neuropathic rats. Taken together, we provide detailed molecular mechanisms for the neuroprotective effect of melatonin and suggest it has translational potential for oxaliplatin-induced neuropathy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Cox, Brian; Chhabra, Avneesh [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); Zuniga, John R. [UT Southwestern Medical Center, Department of Oral and Maxillofacial Surgery, Surgery, Neurology and Neurotherapeutics, Dallas, TX (United States); Panchal, Neeraj [University of Pennsylvania, Department of Oral Maxillofacial Surgery, Philadelphia, PA (United States); Cheng, Jonathan [UT Southwestern Medical Center, Department of Plastic Surgery, Dallas, TX (United States)
This tertiary care experience examines the utility of magnetic resonance neurography (MRN) in the management of peripheral trigeminal neuropathies. Seventeen patients with clinically suspected peripheral trigeminal neuropathies (inferior alveolar nerve and lingual nerve) were imaged uniformly with 1.5-T examinations. MRN results were correlated with clinical and surgical findings in operated patients and the impact on clinical management was assessed. Clinical findings included pain (14/17), sensory changes (15/17), motor changes (2/17) and palpable masses (3/17). Inciting events included prior dental surgery (12/17), trauma (1/17) and idiopathic incidents (4/17). Non-affected side nerves and trigeminal nerves in the intracranial and skull base course were normal in all cases. Final diagnoses on affected sides were nerve inflammation (4/17), neuroma in continuity (2/17), LN transection (1/17), scar entrapment (3/17), infectious granuloma (1/17), low-grade injuries (3/17) and no abnormality (3/17). Associated submandibular gland and sublingual gland oedema-like changes were seen in 3/17 cases because of parasympathetic effects. Moderate-to-excellent MRN-surgical correlation was seen in operated (8/17) patients, and neuroma and nerve transection were prospectively identified in all cases. MRN is useful for the diagnostic work-up of suspected peripheral trigeminal neuropathy patients with significant impact on clinical management and moderate-to-excellent correlation with intra-operative findings. (orig.)
Ge, Shengjie; Xie, Jing; Zheng, Lequn; Yang, Lijuan; Zhu, Hong; Cheng, Xingbo; Shen, Feixia
To investigate the associations between inflammatory markers, serum anti-ganglioside antibodies (anti-GS-ab), serum plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and diabetic peripheral neuropathy (DPN). Study subjects were divided into three groups: normal group (N group) with 101 healthy individuals; diabetes mellitus without peripheral neuropathy group (DM group) with 87 patients; and DPN group with 178 cases. American Nicolet Viking IV electromyography was applied to detect nerve conduction velocity; enzyme linked immunosorbent assay was used to determine the levels of anti-GS-IgG-ab, PAI-1, and TNF-α; and immunoturbidimetry was employed to measure CRP levels. Motor nerve conduction velocity and sensory nerve conduction velocity in the DNC group were significantly lower than in the N and DM groups (all Pdiabetic peripheral neuropathy clinical (DPNC) levels were statistically significant (Panti-GS-ab was positively correlated with DPNC. There were statistically significant differences in PAI-1, TNF-α, and CRP levels between the DPN group and DM and N groups (both P0.05), and the concentration of anti-GS-IgM-ab was in significant positive correlated with PAI-1, TNF-α, and CRP levels. Anti-GS-ab and inflammatory markers such as PAI-1, TNF-α, and CRP were associated with DPN and can be used as important indicators for the prediction and early diagnosis of DPN. Copyright © 2016. Published by Elsevier Ireland Ltd.
Full Text Available Marta Banach,1,* Jakub Antczak,1,* Rafał Rola21Department of Clinical Neurophysiology, 2First Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland *These authors contributed equally to this workBackground: Myotonic dystrophy (DM type 1 and type 2 are inherited diseases characterized by myotonia and myopathy. Additional symptoms include, among others, peripheral neuropathy and sleep-related breathing disorders (SRBDs. There is growing evidence for a complex association between DM1 and DM2, which was described in patients with diabetes mellitus and in the general population. In this study, we investigated whether there is an association between peripheral neuropathy and SRBDs also in the population of patients with DM.Methods: The study included 16 patients with DM1 (mean age, 37.9±14.1 years; 20–69 years and eight patients with DM2 (mean age, 47.6±14.1 years; 20–65 years, who underwent a sensory and motor nerve conduction study (NCS and diagnostic screening for SRBDs. In both groups, the NCS parameters were correlated with respiratory parameters.Results: In both groups, the amplitude of the ulnar sensory nerve action potential (SNAP correlated with the mean arterial oxygen saturation (SaO2. In addition, in the DM2 group, the median SNAP correlated with the mean SaO2. In the DM1 group, the median SNAP and the distal motor latency (DML of the ulnar nerve correlated with the apnea–hypopnea index, while the oxygen desaturation index correlated with the DML of the tibial nerve and with conduction velocity in the sural nerve.Conclusion: Our results indicate a complex association between neuropathy and SRBDs in DM1 and DM2. Axonal degeneration may contribute to nocturnal hypoxemia and vice versa. Neuropathy may contribute to muscle weakness, which in turn may cause respiratory events.Keywords: myotonic dystrophy, SRBD and neuropathy with AHI, SNAP, CMAP
Alimoradi, Houman; Pourmohammadi, Nasir; Mehr, Shahram Ejtemaei; Hassanzadeh, Gholamreza; Hadian, Mohammad Reza; Sharifzadeh, Mohammad; Bakhtiarian, Azam; Dehpour, Ahmad Reza
Vincristine (VCR) as a frequently used antimitotic agent which is commonly prescribed for wide spectrum of neoplasm, causes mixed sensorimotor neuropathy. Several evidences show lithium could be a neuroprotective agent, therefore to assess whether a pretreatment and at subtherapeutic dose it could prevent the peripheral neuropathy produced by VCR, rats were treated with VCR 0.1mg/kg i.p. for 3 alternative doses and / or lithium chloride (20mg/kg or 40 mg/kg i.p. daily from the first day to the day of sacrifice). Erythrocyte lithium concentration (ELC) and plasma lithium concentration (PLC) were measured at the seventh day of study and the day of scarification. After seventh day of lithium administration, PLC and ELC reached to a steady state at subtheraputic dose and they did not significantly change at normal housing situation. Hot plate, open field test and nerve conduction velocity were used to evaluate the sensory and motor neuropathy. Only VCR treated rats showed behavioral, electrophysiological and histological evidences of a mixed sensorimotor neuropathy by significant increase in hot plate latencies and a marked decrease in total distance moved and conduction velocities in both sensory and motor nerves. Lithium at the dose of 20mg/kg and specially 40mg/kg robustly reduced the rate of mortality, general toxicity and was able to ameliorate mixed sensorimotor neuropathy induced by VCR. These results suggest that lithium at dose of 20mg/kg and 40 mg/kg, potentially by its effects on cell survival pathways such as inhibition of glycogen synthase kinase-3 (GSK3β), can prevent both motor and sensory components of VCR neuropathy.
Nicholas J. Anderson
Full Text Available 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.
Pacitto, Alessandra; Paglino, Alessandra; Di Genova, Lorenza; Leonardi, Alberto; Farinelli, Edoardo; Principi, Nicola; di Cara, Giuseppe; Esposito, Susanna
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
Pacitto, Alessandra; Paglino, Alessandra; Di Genova, Lorenza; Leonardi, Alberto; Farinelli, Edoardo; Principi, Nicola; di Cara, Giuseppe
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
Lim, Kil-Byung; Kim, Dong Jun; Noh, Jeong-hyun; Yoo, Jeehyun; Moon, Jung-Wha
(1) To examine the effects of peripheral neuropathy on balance stability in patients with type 2 diabetes, and (2) to assess static and dynamic balance and functional limitations. A cross-sectional study. Outpatient clinic. Subjects with type 2 diabetes and healthy subjects (n = 60) were divided into 3 groups: subjects with diabetes and with established peripheral neuropathy (diabetic peripheral neuropathy [DPN] group) (n = 17), subjects with diabetes and without peripheral neuropathy (diabetic control group) (n = 25), and subjects without diabetes (nondiabetic control [NDC] group) (n = 18). Sensory impairment assessment, motor impairment assessment, and functional limitation assessment were assessed by using the Balance Master system. In motor impairment assessment, left-to-right directional control in the rhythmic weight shift was significantly poorer in the diabetic control group than in the NDC group during slow movement (P = .027). During fast movement, it was poorer in the DPN group than in the NDC group (P = .022). In the unilateral stance test of functional limitation assessment with both eyes open, the mean center of gravity sway velocity was significantly higher in the DPN group than in the NDC group (P = .011 for the left leg standing, P = .008 for the right leg standing) and higher in the DPN group than in the diabetic control group (P = .027 for the right leg standing). In the tandem walk test, walking speed was significantly lower in the DPN group than in the NDC group (P = .033), and end sway was significantly greater in the DPN group than in the NDC group (P = .020). Analysis of the results of this study suggest that functional limitations may occur more in the patients with diabetes and with peripheral neuropathy, and dynamic balance stability may decrease more with the patients with diabetes than with the subjects without diabetes. Further studies on balance rehabilitation that concern dynamic balance stabilities and exercise
Fujita, Shunsuke; Ushio, Soichiro; Ozawa, Nana; Masuguchi, Ken; Kawashiri, Takehiro; Oishi, Ryozo; Egashira, Nobuaki
Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells. Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves. Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12) cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice. These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes.
Full Text Available Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1 agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells.Oxaliplatin (4 mg/kg was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves.Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12 cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26 cells or C-26 cell-implanted mice.These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes.
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
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.
Full Text Available 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.
Bailey, Anne; Wingard, Deborah; Allison, Matthew; Summers, Priscilla; Calac, Daniel
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.
Full Text Available Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN, because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg, pregabalin (3 mg/kg, duloxetine (30 mg/kg or mexiletine (100 mg/kg, but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy.
Nicholas, Patrice K; Voss, Joachim; Wantland, Dean; Lindgren, Teri; Huang, Emily; Holzemer, William L; Cuca, Yvette; Moezzi, Shahnaz; Portillo, Carmen; Willard, Suzanne; Arudo, John; Kirksey, Kenn; Corless, Inge B; Rosa, María E; Robinson, Linda; Hamilton, Mary J; Sefcik, Elizabeth; Human, Sarie; Rivero-Mendez, Marta; Maryland, Mary; Nokes, Kathleen M; Eller, Lucille; Kemppainen, Jeanne; Dawson-Rose, Carol; Brion, John M; Bunch, Elli H; Shannon, Maureen; Nicholas, Thomas P; Viamonte-Ros, Ana; Bain, Catherine A
As part of a larger randomized controlled trial examining the efficacy of an HIV/AIDS symptom management manual (n = 775), this study examined the prevalence of peripheral neuropathy in HIV-infected individuals at 12 sites in the USA, Puerto Rico, and Africa. Neuropathy was reported by 44% of the sample; however, only 29.4% reported initiating self-care behaviors to address the neuropathy symptoms. Antiretroviral therapy was found to increase the frequency of neuropathy symptoms, with an increased mean intensity of 28%. A principal axis factor analysis with Promax rotation was used to assess the relationships in the frequency of use of the 18 self-care activities for neuropathy, revealing three distinct factors: (i) an interactive self-care factor; (ii) a complementary medicine factor; and (iii) a third factor consisting of the negative health items of smoking, alcohol, and street drugs. The study's results suggest that peripheral neuropathy is a common symptom and the presence of neuropathy is associated with self-care behaviors to ameliorate HIV symptoms. The implications for nursing practice include the assessment and evaluation of nursing interventions related to management strategies for neuropathy.
Zanotto, T; Gobbo, S; Bullo, V; Vendramin, B; Duregon, F; Cugusi, L; Di Blasio, A; Furian, L; Silvestre, C; Neunhaeuserer, D; Zaccaria, M; Bergamin, M; Ermolao, A
Kidney transplant recipients (KTRs) present with compromised functional capacity, low levels of physical activity, muscle atrophy, and peripheral nerve dysfunction that may result in high postural instability. This study aimed to compare the static balance control of 19 KTRs with 19 healthy adults (HA). All participants completed the Romberg test on a stabilometric platform with eyes open (EO), eyes closed (EC) and during a dual task (DT) condition. Centre of pressure (COP) measures (COP velocity (COPv) and sway area (SA)), as well as position-based outcomes such as anterior-posterior (AP) and medio-lateral (ML) ranges of COP displacements were recorded. Independent ANCOVA revealed an overall lower performance of KTRs compared to HA (ptask did not further worsen balance performance in KTRs. As impaired postural control is one of the main predictors of falls in elderly subjects, these data might also indicate that this constitutes an equivalent risk factor for falling in middle-aged KTRs. Copyright © 2017. Published by Elsevier B.V.
Pritchard, Nicola; Dehghani, Cirous; Edwards, Katie; Burgin, Edward; Cheang, Nick; Kim, Hannah; Mikhaiel, Merna; Stanton, Gemma; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan
To compare small nerve fiber damage in the central cornea and whorl area in participants with diabetic peripheral neuropathy (DPN) and to examine the accuracy of evaluating these 2 anatomical sites for the diagnosis of DPN. A cohort of 187 participants (107 with type 1 diabetes and 80 controls) was enrolled. The neuropathy disability score (NDS) was used for the identification of DPN. The corneal nerve fiber length at the central cornea (CNFLcenter) and whorl (CNFLwhorl) was quantified using corneal confocal microscopy and a fully automated morphometric technique and compared according to the DPN status. Receiver operating characteristic analyses were used to compare the accuracy of the 2 corneal locations for the diagnosis of DPN. CNFLcenter and CNFLwhorl were able to differentiate all 3 groups (diabetic participants with and without DPN and controls) (P cornea. Quantification of CNFL from the corneal center is as accurate as CNFL quantification of the whorl area for the diagnosis of DPN.
Herrera-Rangel, Aline; Aranda-Moreno, Catalina; Mantilla-Ochoa, Teresa; Zainos-Saucedo, Lylia; Jáuregui-Renaud, Kathrine
Aim. To assess the influence of peripheral neuropathy, gender, and obesity on the postural stability of patients with type 2 diabetes mellitus. Methods. 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. Results. 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. Conclusion. 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. PMID:25258716
Full Text Available 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.
Mozdzanowski, Christopher; Perdrizet, George A
Otic barotrauma (OBT) is an adverse event seen in patients receiving hyperbaric oxygen (HBO2) therapy. After encountering a case of painless tympanic perforation during HBO2 therapy of a diabetic patient with the diagnosis of neuropathic Wagner Grade III foot ulcer, we hypothesized that peripheral neuropathy of the lower extremity may be associated with an increased risk of asymptomatic OBT during HBO2 therapy. The medical records of all HBO2 patients during a one-year period of time were reviewed. Subjects were selected based on otoscopic documentation of OBT and divided into two groups based on the presence or absence of lower extremity peripheral neuropathy. Time to therapeutic compression, presence or absence of ear-related symptoms and modified Teed (mTeed) scores were compared between the two groups. A total of 38 patients with OBT, 18 neuropathic and 20 non-neuropathic, were identified. Asymptomatic OBT occurred more frequently in the neuropathic vs. non-neuropathic group (56% vs. 5%, p < 0.001). mTeed scores were significantly greater in the neuropathic vs. non-neuropathic group (mTeed 1, 30% vs. 61%; mTeed 2, 65% vs. 36%; mTeed 3, 4% vs. 3%; p = 0.032). Mean compression times were shorter in the neuropathic vs. non-neuropathic group (10. 5 +/- 1.8 vs. 14.4 +/- 3.3 minutes, p < 0.001). The presence of peripheral neuropathy of the lower extremity may be associated with a significantly greater incidence of asymptomatic otic barotrauma during HBO2 therapy.
Full Text Available In the practice of a general practitioner, the most common peripheral neuropathy reported by patients is carpal tunnel syndrome followed by cubital tunnel syndrome. Carpal tunnel syndrome results from entrapment of the median nerve at the level of the transverse carpal ligament, and cubital tunnel syndrome is a consequence of a compression on the ulnar nerve at the level of the groove of the humerus. The diagnosis of these syndromes is based on a specific interview, clinical examination and additional examinations. The aim of a clinical examination is to assess sensory disorders and muscle atrophy. Until today, standard additional examinations have been electrophysiological tests. At present, however, they are more and more frequently replaced by high-frequency sonography. As in other types of ultrasound examinations, the assessment of peripheral nerves, including the median and ulnar nerves, is non-invasive, well-tolerated by patients, relatively inexpensive and readily available. The examiner must possess knowledge on nerve topographic anatomy and criteria for ultrasound assessment of peripheral neuropathies. During an ultrasound examination, the following are assessed: shape, cross-sectional area of the nerve trunk, its echogenicity, vascularity and relation to adjacent tissues. Motor and sensorimotor nerves may also be assessed indirectly by analysing ultrasound images of the skeletal muscle innervated by these nerves. Furthermore, an important element of an ultrasound examination is dynamic assessment of the nerves. Carpal and cubital tunnel syndromes belong to so-called entrapment neuropathies whose common sonographic features are nerve oedema and hyperaemia proximally to the compression site.
Mu eYang; Corentin ePeyret; XiangQun eShi; Nicolas eSiron; Jeong Ho eJang; Sonia eWu; Sylvie eFournier; Ji eZhang
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 m...
Full Text Available 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 indicate 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 neuropathy. 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.
Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji
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.
Silva, Susana F.; Gouveia, Sofia; Gomes, Leonor; Negrão, Luís; João Quadrado, Maria; Domingues, José Paulo; Morgado, António Miguel
Diabetic peripheral neuropathy (DPN) is one common complication of diabetes. Early diagnosis of DPN often fails due to the non-availability of a simple, reliable, non-invasive method. Several published studies show that corneal confocal microscopy (CCM) can identify small nerve fibre damage and quantify the severity of DPN, using nerve morphometric parameters. Here, we used image texture features, extracted from corneal sub-basal nerve plexus images, obtained in vivo by CCM, to identify DPN patients, using classification techniques. A SVM classifier using image texture features was used to identify (DPN vs. No DPN) DPN patients. The accuracies were 80.6%, when excluding diabetic patients without neuropathy, and 73.5%, when including diabetic patients without diabetic neuropathy jointly with healthy controls. The results suggest that texture analysis might be used as a complementing technique for DPN diagnosis, without requiring nerve segmentation in CCM images. The results also suggest that this technique has enough sensitivity to detect early disorders in the corneal nerves of diabetic patients.
Tey, S; Ahmad-Annuar, A; Drew, A P; Shahrizaila, N; Nicholson, G A; Kennerson, M L
The cytoplasmic dynein-dynactin genes are attractive candidates for neurodegenerative disorders given their functional role in retrograde transport along neurons. The cytoplasmic dynein heavy chain (DYNC1H1) gene has been implicated in various neurodegenerative disorders, and dynactin 1 (DCTN1) genes have been implicated in a wide spectrum of disorders including motor neuron disease, Parkinson's disease, spinobulbar muscular atrophy and hereditary spastic paraplegia. However, the involvement of other dynactin genes with inherited peripheral neuropathies (IPN) namely, hereditary sensory neuropathy, hereditary motor neuropathy and Charcot-Marie-Tooth disease is under reported. We screened eight genes; DCTN1-6 and ACTR1A and ACTR1B in 136 IPN patients using whole-exome sequencing and high-resolution melt (HRM) analysis. Eight non-synonymous variants (including one novel variant) and three synonymous variants were identified. Four variants have been reported previously in other studies, however segregation analysis within family members excluded them from causing IPN in these families. No variants of disease significance were identified in this study suggesting the dynactin genes are unlikely to be a common cause of IPNs. However, with the ease of querying gene variants from exome data, these genes remain worthwhile candidates to assess unsolved IPN families for variants that may affect the function of the proteins. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Handsaker, Joseph C; Brown, Steven J; Bowling, Frank L; Cooper, Glen; Maganaris, Constantinos N; Boulton, Andrew J M; Reeves, Neil D
Although patients with diabetic peripheral neuropathy (DPN) are more likely to fall than age-matched controls, the underlying causative factors are not yet fully understood. This study examines the effects of diabetes and neuropathy on strength generation and muscle activation patterns during walking up and down stairs, with implications for fall risk. Sixty-three participants (21 patients with DPN, 21 diabetic controls, and 21 healthy controls) were examined while walking up and down a custom-built staircase. The speed of strength generation at the ankle and knee and muscle activation patterns of the ankle and knee extensor muscles were analyzed. Patients with neuropathy displayed significantly slower ankle and knee strength generation than healthy controls during stair ascent and descent (P stairs. These changes, which are likely caused by altered activations of the extensor muscles, increase the likelihood of instability and may be important contributory factors for the increased risk of falling. Resistance exercise training may be a potential clinical intervention for improving these aspects and thereby potentially reducing fall risk. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Weyns, F; Bringmans, T; Vandevenne, J; Daenekindt, T; Van Goethem, A; Wuyts, J; Vanormelingen, L; Vandersteen, M
Clinical compression neuropathy caused by para-articular cysts is rare. Only recently, the unifying articular theory was proposed to clarify its true etiologic nature. The authors attribute 17 cases to this theory in order to illustrate the shift in the diagnostic and treatment protocol, and the possible impact on patient outcome. Eight intraneural and nine extraneural cysts were included. The proposed diagnostic protocol includes electromyography and ultrasound, followed by magnetic resonance imaging to characterize the cyst. The proposed treatment protocol consists of (1) ligation of the pedicle connecting the cyst with the afflicted joint, (2) decompression of the nerve and, when needed and (3) disarticulation of the superior tibiofibular joint (in case of peroneal nerve involvement). Outcome was good to excellent in all patients, with recovery of sensory and motor function. Cyst recurrence was observed in three intraneural cases (18 %). Analysis of our own diagnostic protocol showed that atypical compression neuropathies should follow a strict diagnostic protocol to exclude missing the presence of a cyst. Ultrasound needs to play a crucial role, with MRI for cyst characterization and pedicle identification. Retrospective proof in favor of the articular theory was found in all cases. An explanation for the cyst recurrences was formed based on the articular theory. In addition, a diagnostic and therapeutic protocol is proposed for all atypical peripheral compression neuropathies with the ultimate goal to achieve optimal patient outcome.
Vahdat, Linda T.; Garcia, Agustin A.; Vogel, Charles; Pellegrino, Christine; Lindquist, Deborah L.; Iannotti, Nicholas; Gopalakrishna, Prashanth; Sparano, Joseph A.
Peripheral neuropathy is a common toxicity associated with tubulin-targeted chemotherapeutic agents. This Phase II study compares the incidence and severity of neuropathy associated with eribulin mesylate or ixabepilone in metastatic breast cancer (MBC). The primary objective was to assess the incidence of neuropathy; the study was designed to detect a difference in neuropathy rate of 35?% for eribulin versus 63?% for ixabepilone (odds ratio 0.316, 80?% power, 0.05 two-sided significance leve...
Full Text Available Diabetes mellitus is not only a clinical syndrome characterizing hyperglycemia, but is also a cause of debilitating problem known as peripheral neuropathy (PN. This review addresses the importance of diagnosing PN in a clinical setting as PN causes pain and discomfort in lower extremities, loss or absence of protective sensations in the lower extremities leading to balance problems, risk of foot ulcerations, and a reduced quality of life in adults with type 2 diabetes. A variety of modalities or methods are available to evaluate both subjective and objective measures of peripheral nerve functions, and have been discussed in detail in this review. It is of utmost importance to understand that evaluating PN as a routine practice in a simple way may also play a vitally important role in preventing foot ulcers or fall-related morbidity and mortality in adults with type 2 diabetes.
Zhang, Haijun; Dougherty, Patrick M
The mechanism of chemotherapy-induced peripheral neuropathy after paclitaxel treatment is not well understood. Given the poor penetration of paclitaxel into central nervous system, peripheral nervous system is most at risk. Intrinsic membrane properties of dorsal root ganglion neurons were studied by intracellular recordings. Multiple-gene real-time polymerase chain reaction array was used to investigate gene expression of dorsal root ganglion neuronal ion channels. Paclitaxel increased the incidence of spontaneous activity from 4.8 to 27.1% in large-sized and from 0 to 33.3% in medium-sized neurons. Paclitaxel decreased the rheobase (nA) from 1.6 ± 0.1 to 0.8 ± 0.1 in large-sized, from 1.5 ± 0.2 to 0.6 ± 0.1 in medium-sized, and from 1.6 ± 0.2 to 1.0 ± 0.1 in small-sized neurons. After paclitaxel treatment, other characteristics of membrane properties in each group remained the same except that Aδ neurons showed shorter action potential fall time (ms) (1.0 ± 0.2, n = 10 vs. 1.8 ± 0.3, n = 9, paclitaxel vs. vehicle). Meanwhile, real-time polymerase chain reaction array revealed an alteration in expression of some neuronal ion channel genes including up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 1 (fold change 1.76 ± 0.06) and Nav1.7 (1.26 ± 0.02) and down-regulation of Kir channels (Kir1.1, 0.73 ± 0.05, Kir3.4, 0.66 ± 0.06) in paclitaxel-treated animals. The increased neuronal excitability and the changes in gene expression of some neuronal ion channels in dorsal root ganglion may provide insight into the molecular and cellular basis of paclitaxel-induced neuropathy, which may lead to novel therapeutic strategies.
... SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Diabetic neuropathy is a peripheral nerve disorder caused by diabetes or poor blood sugar control. The most common ...
Full Text Available Professional management of paediatric diabetology, according to consensus guidelines, involves the screening of micro-vascular complications at puberty. The subclinical form of peripheral neural dysfunction in diabetic teenagers is reported with a frequency of 50-88%, by different authors. The purpose of this study was to evaluate the frequency of subclinical distal neuropathy (DSMN in type 1 diabetic pediatric patients during the second decade of life, and its relationship with metabolic control. The Endocrinology Department and the Neurology-Physiology Laboratory of the Pediatric Clinic in Belgrade carried out a longitudinal follow-up study (lasting 18 months, beginning in November 2000 on a selection of patients with poor metabolic control. During routine clinical treatment, patients were evaluated using the electrophysiological diagnostic method on peripheral neural dysfunction, a subclinical form of neuropathy. Metabolic control was manifested through HbA1c levels, measured every 3 months, using ion-exchange chromatography. Finally, here is the data collected from the clinical follow-up investigation of 60 children, aged 13-19 (median 1S.S±2.2, with duration of diabetes from 2-16 years (median b.3±3.b, and on the following therapies: 43 CT-conventional and 17 IIT-intensive, and insulin dose/day, median 1.02 (0.6-2.1 U/kg. Detected DSMN parameters at the beginning and at the end of the study were also noted. DSMN frequency was positive, at 64% for HbA1c of 9.44; DSMN dysfunction was reversed in 5% of the patients, for HbA1c of 10.17; the worst result was the progression of DSMN at 6.7% for HbA1c of 10.52; 6.7% had negative DSMN, with improved metabolic control, for HbA1c of 8.4; 15% of the examinations were unfinished (+/*. ANOVA statistical analysis showed a significant statistical relationship between metabolic control (HbA1c levels and DSMN neuropathy (sig. 0.043, p<0.05. There was no significant relationship between the reversion of
Kinsella, T.J.; DeLuca, A.M.; Barnes, M.; Anderson, W.; Terrill, R.; Sindelar, W.F. (National Cancer Institute, Bethesda, MD (USA))
Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers and perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy.
... know when you have a small blister or sore on your feet. Numbness may make it harder to tell where ... Numbness in the feet can lead to skin sores that do not heal. In rare cases, numbness in the feet may lead to amputation. There is no cure ...
Byung Kil Ha
Full Text Available BackgroundBrachial-ankle pulse wave velocity (baPWV is known to be a good surrogate marker of clinical atherosclerosis. Atherosclerosis is a major predictor for developing neuropathy. The goal of this study was to determine the relationship between baPWV and diabetic peripheral neuropathy (DPN in patients with type 2 diabetes.MethodsA retrospective cross-sectional study was conducted involving 692 patients with type 2 diabetes. The correlation between increased baPWV and DPN, neurological symptoms, and neurological assessment was analyzed. DPN was examined using the total symptom score (TSS, ankle reflexes, the vibration test, and the 10-g monofilament test. DPN was defined as TSS ≥2 and an abnormal neurological assessment. Data were expressed as means±standard deviation for normally distributed data and as median (interquartile range for non-normally distributed data. Independent t-tests or chi-square tests were used to make comparisons between groups, and a multiple logistic regression test was used to evaluate independent predictors of DPN. The Mantel-Haenszel chi-square test was used to adjust for age.ResultsPatients with DPN had higher baPWV and systolic blood pressure, and were more likely to be older and female, when compared to the control group. According to univariate analysis of risk factors for DPN, the odds ratio of the baPWV ≥1,600 cm/sec was 1.611 (95% confidence interval [CI], 1.072 to 2.422; P=0.021 and the odds ratio in female was 1.816 (95% CI, 1.195 to 2.760; P=0.005.ConclusionIncreased baPWV was significantly correlated with peripheral neuropathy in patients with type 2 diabetes.
Full Text Available Background: A suspected peripheral neuropathy outbreak was reported from Dechentsemo Central School, Thinleygang, Punakha, following which the investigation team was immediately dispatched in the field. Objective: The aim of investigation was to ascertain the cause and risk factor for the outbreak in order to implement control measures. Methods: A case control study was devised for the investigation to study about the past exposure or deficiencies in order to find out the suspected cause and risk factors. A semi-quantitative food frequency questionnaire was administered to both cases and controls to collect information on the type of food they have consumed. The information garnered was analyzed using Chi-Square or Fischer Exact test for categorical variables and Man-Whitney U-test for quantitative variables. Results: All 17 cases were females with mean age of 13 years (SD 2.7 years. The average daily amount of thiamine intake was 0.6 mg/day for case and 0.8 mg/day for controls against the recommended daily allowance (RDA of 1.2 mg/day. Case and control patients differed significantly with respect to fat intake (p-value = 0.02, more strongly with folate and iron intake (p-value < 0.01. Conclusion: The outbreak of peripheral neuropathy in Dechentsemo Central School appears to be linked to reduced dietary intake rich in vitamin B1 coupled with low intake of folate and iron in their diet.
Full Text Available Purpose. The aim of this paper is to review the published studies on the characteristics of impairments in the postural control and gait performance in diabetic peripheral neuropathy (DPN. Methods. A review was performed by obtaining publication of all papers reporting on the postural control and gait performance in DPN from Google Scholar, Ovid, SAGE, Springerlink, Science Direct (SD, EBSCO Discovery Service, and Web of Science databases. The keywords used for searching were “postural control,” “balance,” “gait performance,” “diabetes mellitus,” and “diabetic peripheral neuropathy.” Results. Total of 4,337 studies were hit in the search. 1,524 studies were screened on their titles and citations. Then, 79 studies were screened on their abstract. Only 38 studies were eligible to be selected: 17 studies on postural control and 21 studies on the gait performance. Most previous researches were found to have strong evidence of postural control impairments and noticeable gait deficits in DPN. Deterioration of somatosensory, visual, and vestibular systems with the pathologic condition of diabetes on cognitive impairment causes further instability of postural and gait performance in DPN. Conclusions. Postural instability and gait imbalance in DPN may contribute to high risk of fall incidence, especially in the geriatric population. Thus, further works are crucial to highlight this fact in the hospital based and community adults.
Full Text Available Nephropathy, retinopathy cardiomyopathy and peripheral neuropathy are all recognized as important complications in about 50% of diabetes mellitus (DM patients, mostly related to a poor glycemic control or to an improper management of this pathology. In any case, amongst others, diabetic peripheral neuropathy (DPN seems the leading and most painful complication usually affecting many DM patients. For this reason, this work was conceived to review the large variety of strategies adopted for management of DPN, starting from the most conventional therapies to arrive at alternative approaches. From this perspective, both the most popular pharmacological treatments used to respond to the poorly effect of common analgesics—non-steroidal anti-inflammatory drugs (NSAIDS and opioids—understood as gabapentin vs. pregabalin clinical use, and the guidelines provided by Oriental Medicine as well as by a long list of natural compounds that many authors identify as possible therapeutic or alternative agents to replace or to combine with the existing therapies will be included. Moreover, in the effort to provide the widest panel of remedies, the most antique techniques of acupuncture and electrostimulation will be considered as alternative, which are useful approaches to take into account in any non-pharmacological strategy for DPN management.
Mustapa, Amirah; Justine, Maria; Mohd Mustafah, Nadia; Jamil, Nursuriati; Manaf, Haidzir
Purpose. The aim of this paper is to review the published studies on the characteristics of impairments in the postural control and gait performance in diabetic peripheral neuropathy (DPN). Methods. A review was performed by obtaining publication of all papers reporting on the postural control and gait performance in DPN from Google Scholar, Ovid, SAGE, Springerlink, Science Direct (SD), EBSCO Discovery Service, and Web of Science databases. The keywords used for searching were "postural control," "balance," "gait performance," "diabetes mellitus," and "diabetic peripheral neuropathy." Results. Total of 4,337 studies were hit in the search. 1,524 studies were screened on their titles and citations. Then, 79 studies were screened on their abstract. Only 38 studies were eligible to be selected: 17 studies on postural control and 21 studies on the gait performance. Most previous researches were found to have strong evidence of postural control impairments and noticeable gait deficits in DPN. Deterioration of somatosensory, visual, and vestibular systems with the pathologic condition of diabetes on cognitive impairment causes further instability of postural and gait performance in DPN. Conclusions. Postural instability and gait imbalance in DPN may contribute to high risk of fall incidence, especially in the geriatric population. Thus, further works are crucial to highlight this fact in the hospital based and community adults.
Wan, Eric L; Rivadeneira, Andres F; Jouvin, Renato Martinez; Dellon, A Lee
Plastic surgery has a tradition of caring for patients with facial deformity and hand deformity related to leprosy. The approach, however, to the progressive deformity and disability related to chronic nerve compression is underappreciated in the world today. A cohort of patients with leprous neuropathy from an indigenous area of leprosy in Ecuador was evaluated for the presence of chronic peripheral nerve compression, and 12 patients were chosen for simultaneous upper and lower extremity, unilateral, nerve decompression at multiple levels along the course of each nerve. The results at 1 year of follow-up show that 6 patients improved into the excellent category and 4 patients improved into the good category for improved function. Based on the early results in this small cohort of patients with leprous neuropathy, an approach to peripheral nerve decompression, encompassing the concept of multiple crush at multiple levels of each nerve, seems to offer optimism to improve upper and lower extremity limb function. Long-term studies with quality-of-life outcomes would be welcome.
Pieber, Karin; Herceg, Malvina; Paternostro-Sluga, Tatjana
To review different types of electrotherapy for the treatment of painful diabetic peripheral neuropathy. A structured search of the electronic database MEDLINE was performed from the time of its initiation to July 2009. Articles in English and German were selected. The efficacy of different types of electrotherapy for painful diabetic peripheral neuropathy has been evaluated in 15 studies; the effects of transcutaneous electrical nerve stimulation are consistent. The beneficial effects of prolonged use have been reported in three large studies and one small study. The effects of frequency-modulated electromagnetic neural stimulation were assessed in one large study, and a significant reduction in pain was reported. Treatment with pulsed and static electromagnetic fields has been investigated in two small and three large studies, and analgesic benefits have been reported. In one large study focusing on pulsed electromagnetic fields, no beneficial effect on pain was registered. Only small studies were found concerning other types of electrotherapy, such as pulsed-dose electrical stimulation, high-frequency external muscle stimulation or high-tone external muscle stimulation. The conclusions drawn in these articles are diverse. Shortcomings and problems, including a poor study design, were observed in some. Further randomized, double-blind, placebo-controlled studies comprising larger sample sizes, a longer duration of treatment, and longer follow-up assessments are required.
Zeng, Xiaopei L; Nagavalli, Anil; Smith, Colin-Jamal; Howard, James F; Su, Maureen A
Chronic inflammatory demyelinating polyneuropathy results from autoimmune destruction of the peripheral nervous system and is a component of the multiorgan autoimmunity syndrome that results from Aire gene mutations in humans. In parallel, peripheral nervous system autoimmunity resembling chronic inflammatory demyelinating polyneuropathy develops spontaneously in NOD mice with a partial loss of Aire function (NOD.Aire(GW/+) mice) and is a T cell-mediated disease. In this study, we analyze how key aspects of T cell activation and function modulate disease development in Aire-deficient mice. We show that genetic ablation of the Th1 cytokine IFN-γ completely prevents clinical and electrophysiological evidence of neuropathy in NOD.Aire(GW/+) mice. IFN-γ deficiency is associated with absence of immune infiltration and decreased expression of the T cell chemoattractant IP-10 in sciatic nerves. Thus, IFN-γ is absolutely required for the development of autoimmune peripheral neuropathy in NOD.Aire(GW/+) mice. Because IFN-γ secretion is enhanced by B7-CD28 costimulation of T cells, we sought to determine the effects of these costimulatory molecules on neuropathy development. Surprisingly, B7-2 deficiency accelerated neuropathy development in NOD.Aire(GW/+) mice, and Ab blockade of both B7-1 and B7-2 resulted in fulminant, early-onset neuropathy. Thus, in contrast to IFN-γ, B7-2 alone and B7-1/B7-2 in combination function to ameliorate neuropathy development in NOD.Aire(GW/+) mice. Together, these findings reveal distinct and opposing effects of the T cell costimulatory pathway and IFN-γ production on the pathogenesis of autoimmune peripheral neuropathy.
Walter-Höliner, Isabella; Barbarini, Daniela Seick; Lütschg, Jürg; Blassnig-Ezeh, Anya; Zanier, Ulrike; Saely, Christoph H; Simma, Burkhard
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.
Full Text Available "n Background and the purpose of the study: Diabetic neuropathy is the most common diabetic complication that often is accompanied by significant morbidity, mortality and economic burden. The purpose of this study was evaluation of effect of Semelil (ANGIPARSTM, a new herbal drug for treatment of diabetic foot ulcers or diabetic peripheral neuropathy. "nMethods: In this double blind clinical trial, 49 type 2 diabetes patients with different degrees of neuropathy were evaluated in two groups (ANGIPARSTM and placebo groups. All patients were assessed at the start and 12 weeks after treatment, with laboratory tests, United Kingdom screening test, Michigan neuropathy screening score, Michigan diabetic neuropathy score, vibration perception thresholds, nerve conduction study, monofilament test and visual analog scale. "nResults: Michigan diabetic neuropathy score was decreased notably in ANGIPARSTM group. In the nerve conduction study, appropriate meaningful changes were observed in the distal latency and amplitude in the motor Ulnar nerve in ANGIPARSTM group. Conclusion: The results showed limited evidence of efficacy of ANGIPARSTM in diabetic neuropathy treatment and more studies with a larger sample size and longer duration are required.
Kornhuber, Malte E.; Clajus, Carolina; Alston, Charlotte L.; Wienke, Andreas; Deschauer, Marcus; Taylor, Robert W.; Zierz, Stephan
Objective: To characterize peripheral nerve involvement in patients with chronic progressive external ophthalmoplegia (CPEO) with single and multiple mitochondrial DNA (mtDNA) deletions, based on clinical scores and detailed nerve conduction studies. Methods: Peripheral nerve involvement was prospectively investigated in 33 participants with CPEO (single deletions n = 18 and multiple deletions n = 15). Clinically, a modified Total Neuropathy Score (mTNS) and a modified International Cooperative Ataxia Rating Scale (mICARS) were used. Nerve conduction studies included Nn. suralis, superficialis radialis, tibialis, and peroneus mot. Early somatosensory evoked potentials were obtained by N. tibialis stimulation. Results: Participants with multiple deletions had higher mTNS and mICARS scores than those with single deletions. Electrophysiologically in both sensory nerves (N. suralis and N. radialis superficialis), compound action potential (CAP) amplitudes and nerve conduction velocities were lower and mostly abnormal in multiple deletions than those in single deletions. Early somatosensory evoked potentials of N. tibialis revealed increased P40 latencies and decreased N35-P40 amplitudes in multiple deletions. Both sensory nerves had higher areas under the receiver operating characteristic curves for the decreased CAP amplitudes than the 2 motor nerves. The N. suralis had the best Youden index, indicating a sensitivity of 93.3% and a specificity of 72.2% to detect multiple deletions. Conclusions: Peripheral nerve involvement in participants with multiple mtDNA deletions is an axonal type of predominant sensory neuropathy. This is clinically consistent with higher mTNS and mICARS scores. Sensory nerve involvement in participants with multiple deletions was not correlated with age at onset and duration of disease. PMID:27822509
van Vliet, Peter; Berden, Annelies E; van Schie, Mojca K M; Bakker, Jaap A; Heringhaus, Christian; de Coo, Irenaeus F M; Langeveld, Mirjam; Schroijen, Marielle A; Arbous, M Sesmu
A combination of unexplained peripheral neuropathy, hypoparathyroidism, and the inability to cope with metabolic stress could point to a rare inborn error of metabolism, such as mitochondrial trifunctional protein (MTP) deficiency.Here, we describe a 20-year-old woman who was known since childhood with axonal motor sensory polyneuropathy of unknown origin. She presented with progressive dyspnoea, and increased muscle weakness, preceded by 6 days of fever, vomiting, and diarrhoea. Laboratory testing showed rhabdomyolysis, and hypocalcaemia with low parathyroid levels. The patient was intubated because of respiratory insufficiency and a viral and bacterial pneumonia was diagnosed. She was discharged after 16 days of admission. Metabolic screening, performed at the time of rhabdomyolysis, showed increased concentrations of long-chain 3-hydroxyacyl carnitine species, together with elevated urinary excretion of 3-hydroxy dicarboxylic acids. Decreased activity of long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-ketoacyl-CoA thiolase in peripheral lymphocytes and fibroblasts confirmed a MTP deficiency. Sequence analysis of the HADHB gene showed two heterozygous variants: c.209+1G>C (splicing defect) and c.980T>C (p.Leu327Leu). When the acylcarnitine profile was repeated after the episode of rhabdomyolysis had resolved it showed no abnormalities.Our case illustrates a cluster of peripheral neuropathy, episodic rhabdomyolysis, and hypoparathyroidism in a patient with MTP deficiency caused by mutations in the HADHB gene. It stresses the importance of performing metabolic screening when patients are most symptomatic, as normal results can be found at times when no metabolic stress is present. Screening is relatively easy and timely diagnosis has important implications for treatment.
Hong, J S; Tian, J; Wu, L H
In the present study, we aimed to investigate the effects of chemotherapy-induced peripheral neurotoxicity (cipn) on psychological distress and sleep quality in cancer patients. A total of 706 cancer patients were interviewed for the study. In the 4th week of treatment, patient cipn was measured using the Patient Neurotoxicity Questionnaire (pnq). The sleep quality and psychological distress of patients were measured using the Pittsburgh Sleep Quality Index (psqi), the Distress Thermometer (dt), and the Hospital Anxiety and Depression Scale (hads). Multiple logistic regression was applied to determine the independent effects of cipn on psychological distress and sleep disturbance in the patients. THESE CORRELATION COEFFICIENTS WERE OBTAINED: 0.387 (p sleep quality in the five pnq grades were statistically significantly different (p grades were found to be associated with depression (p sleep quality (p sleep quality in cancer patients treated with chemotherapy. High pnq grades were significantly associated with poor psychological status and sleep quality. Our results emphasize the importance of assessing peripheral neuropathies during chemotherapy and of adjusting treatment plans based on assessment results.
Zeng, Xiaopei L.; Nagavalli, Anil; Smith, Colin-Jamal; Howard, James F.; Su, Maureen A.
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) results from autoimmune destruction of the peripheral nervous system (PNS) and is a component of the multi-organ autoimmunity syndrome which results from Autoimmune Regulator (Aire) gene mutations in humans. In parallel, PNS autoimmunity resembling CIDP develops spontaneously in NOD mice with a partial loss of Aire function (NOD.AireGW/+ mice), and is a T cell-mediated disease. In this study, we analyze how key aspects of T cell activation and function modulate disease development in Aire-deficient mice. We show here that genetic ablation of the Th1 cytokine IFNγ completely prevents clinical and electrophysiological evidence of neuropathy in NOD.AireGW/+ mice. IFNγ deficiency is associated with absence of immune infiltration and decreased expression of the T cell chemoattractant IP-10 in sciatic nerves. Thus, IFNγ is absolutely required for the development of autoimmune peripheral neuropathy in NOD.AireGW/+ mice. Because IFNγ secretion is enhanced by B7-CD28 costimulation of T cells, we sought to determine the effects of these costimulatory molecules on neuropathy development. Surprisingly, B7-2 deficiency accelerated neuropathy development in NOD.AireGW/+ mice, and antibody blockade of both B7-1 and B7-2 resulted in fulminant, early-onset neuropathy. Thus, in contrast to IFNγ, B7-2 alone and B7-1/B7-2 in combination function to ameliorate neuropathy development in NOD.AireGW/+ mice. Together, these findings reveal distinct and opposing effects of T cell costimulatory pathways and IFNγ production on the pathogenesis of autoimmune peripheral neuropathy. PMID:23487421
Pellegrino, J.E.; Spinner, N.B.; Zackai, E.H. [Childrens Hospital of Philadelphia, PA (United States)] [and others
We report on a patient with dup(17p) and monosomy (10q) resulting from a familial translocation. Manifestations typical of both syndromes were present. The overall development of this patient was better by comparison with similar reported cases of either anomaly. Our evaluation detected severe gross motor delay and signs of a demyelinating peripheral neuropathy. This patient is trisomic for the region of 17p which includes the peripheral myelin protein-22 (PMP-22) gene, known to be duplicated in Charcot-Marie-Tooth neuropathy type 1A (CMT1A). Our analysis in this patient suggests that trisomy for the PMP-22 gene led to the demyelinating neuropathy and contributed to his severe motor development delay. 33 refs., 3 figs., 1 tab.
Ahmed, Marwan A; Muntingh, George; Rheeder, Paul
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 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 3.88, P = 0.053). Close to third of metformin
Mijnhout, Gerritje S.; Kollen, Boudewijn J.; Alkhalaf, Alaa; Kleefstra, Nanno; Bilo, Henk J. G.
Objective. We performed a systematic review of the literature to evaluate the effects of alpha lipoic acid for symptomatic peripheral neuropathy in patients with diabetes mellitus. Research design and methods. The databases MEDLINE and EMBASE were searched using the key words "lipoic acid",
Jønsson, V; Jensen, T S; Friis, M L
biopsies provide a simple effective method of detecting immunoglobulin binding to peripheral nerves in patients suspected of having an autoimmune neuropathy. In contrast to sural nerve biopsy, skin biopsy does not cause sensory loss or pain in a denervated area and can easily be repeated....
Toosizadeh, Nima; Mohler, Jane; Armstrong, David G; Talal, Talal K; Najafi, Bijan
Poor balance control and increased fall risk have been reported in people with diabetic peripheral neuropathy (DPN). Traditional body sway measures are unable to describe underlying postural control mechanism. In the current study, we used stabilogram diffusion analysis to examine the mechanism under which balance is altered in DPN patients under local-control (postural muscle control) and central-control (postural control using sensory cueing). DPN patients and healthy age-matched adults over 55 years performed two 15-second Romberg balance trials. Center of gravity sway was measured using a motion tracker system based on wearable inertial sensors, and used to derive body sway and local/central control balance parameters. Eighteen DPN patients (age = 65.4±7.6 years; BMI = 29.3±5.3 kg/m2) and 18 age-matched healthy controls (age = 69.8±2.9; BMI = 27.0±4.1 kg/m2) with no major mobility disorder were recruited. The rate of sway within local-control was significantly higher in the DPN group by 49% (healthy local-controlslope = 1.23±1.06×10-2 cm2/sec, Pcontrol balance behavior in DPN patients. Unlike local-control, the rate of sway within central-control was 60% smaller in the DPN group (healthy central-controlslope-Log = 0.39±0.23, Pcontrol rate of sway with neuropathy severity (rPearson = 0.65-085, Pdiabetes (rPearson = 0.58-071, Pcontrols. However, as soon as they perceived the magnitude of sway using sensory feedback, they chose a high rigid postural control strategy, probably due to high concerns for fall, which may increase the energy cost during extended period of standing; the adaptation mechanism using sensory feedback depends on the level of neuropathy and the history of diabetes.
Akram Hussain Bijli
Full Text Available Background: To validate the effectiveness of indigenously designed “footboard (FB” in early diagnosis of diabetic peripheral neuropathy (PNP by comparing it with Semmes–Weinstein monofilament (SWM and vibration perception (VP. Materials and Methods: Two hundred and forty-four patients with diabetes were examined for PNP using SWM and 128 Hz tuning fork. The findings were compared with indigenously designed FBs with 1, 2, and 3 mm elevations. Results: Out of 108 patients who did not have protective sensation as per SWM, only 10 (9.2% felt 1 mm board bearings, and out of 72 patients who did not feel vibration, only 8 (11.1% felt 1 mm board bearings. Out of 136 patients who had protective sensation, 128 (94.11% felt 2 mm elevated board bearings, and out of 172 patients who had VP, only 152 patients (88.3% felt 2 mm board bearings. With SWM as standard, the sensitivities and specificities, respectively, were 63% and 90% (1 mm board, and 94% and 60% (2 mm board. With VP, the sensitivities and specificities, respectively, were 59% and 90% (1 mm board, and 88% and 61% (2 mm board. Conclusions: FB, which simultaneously tests touch and pressure sensation, shows a high level of performance in detecting at-risk feet. FB may be simple, time-efficient, and inexpensive test for detection of neuropathy and needs further validation in a larger study.
Wang, Dongye; Zhang, Xiang; Lu, Liejing; Li, Haojiang; Zhang, Fang; Chen, Yueyao; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong (China)
To determine the role of magnetic resonance (MR) imaging and quantitative T2 value measurements in the assessment of diabetic peripheral neuropathy (DPN). Sequential MR imaging, T2 measurement, and quantitative sensory testing of sciatic nerves were performed in streptozotocin-induced diabetic rats (n = 6) and normal control rats (n = 6) over a 7-week follow-up period. Histological assessment was obtained from 48 diabetic rats and 48 control rats once weekly for 7 weeks (n = 6 for each group at each time point). Nerve signal abnormalities were observed, and the T2 values, mechanical withdrawal threshold (MWT), and histological changes were measured and compared between diabetic and control animals. Sciatic nerves in the diabetic rats showed a gradual increase in T2 values beginning at 2 weeks after the induction (P = 0.014), while a decrease in MWT started at 3 weeks after the induction (P = 0.001). Nerve T2 values had a similar time course to sensory functional deficit in diabetic rats. Histologically, sciatic nerves of diabetic rats demonstrated obvious endoneural oedema from 2 to 3 weeks after the induction, followed by progressive axonal degeneration, Schwann cell proliferation, and coexistent disarranged nerve regeneration. Nerve T2 measurement is potentially useful in detecting and monitoring diabetic neuropathy. (orig.)
Yigit, Serbulent; Karakus, Nevin; Inanir, Ahmet
Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. Methylenetetrahydrofolate reductase (MTHFR) gene variants have been associated with vasculopathy that has been linked to diabetic neuropathy. The aim of the present study was to investigate the possible association between MTHFR gene C677T mutation and DPN and evaluate if there is an association with clinical features in a relatively large cohort of Turkish patients. The study included 230 patients affected by DPN and 282 healthy controls. Genomic DNA was isolated and genotyped using the polymerase chain reaction-based restriction fragment length polymorphism assay for the MTHFR gene C677T mutation. The genotype and allele frequencies of the C677T mutation showed statistically significant differences between the patients with DPN and the controls (p=0.003 and p=0.002, respectively). After the patients with DPN were stratified according to clinical and demographic characteristics, a significant association was observed between the C677T mutation and history of retinopathy (p=0.039). A high association between the MTHFR gene C677T mutation and DPN was observed in the present study. In addition, history of retinopathy was associated with the MTHFR C677T mutation in patients with DPN.
Alessandra Madia Mantovani
Full Text Available Abstract Diabetic peripheral neuropathy (DPN is a common complication of diabetes mellitus when glycemic levels are poorly controlled. Sometimes DPN is accompanied by vasculopathy (DPV, which can worsen the clinical prognosis. The aim of this study was to analyze the gait parameters of nondiabetic individuals and diabetic individuals with DPN with or without DPV. METHOD The study included 68 individuals (50 to 65 years old divided into three groups: people without diabetes mellitus (n = 33, diabetic patients with DPN (n = 18, and diabetic patients with both DPN and DVP (n = 17. The participants underwent a gait evaluation using electronic baropodometry to obtain the single and double support, velocity, and pressure-time integral. RESULTS The pressure-time integral, velocity, and single support variables were lower, and the double support and double support/single support ratio were higher in the diabetic neuropathy and vasculopathy group. The velocity was lower the greater the degree of impairment of the diabetic foot. Some correlations were identified with velocity. CONCLUSION In diabetic individuals, there was a significant worsening of the gait parameters analyzed according to increasing degree of clinical impairment.
Matsuo, Mitsuhiro; Ito, Hisakatsu; Takemura, Yoshinori; Hattori, Mizuki; Kawakami, Masaaki; Takahashi, Norimasa; Yamazaki, Mitsuaki
Paclitaxel-induced peripheral neuropathy (PIPN) is one of the serious adverse events associated with paclitaxel-based cancer treatments. A recent case study showed that the antiplatelet agent clopidogrel inhibits paclitaxel metabolism via cytochrome P450 (CYP) 2C8, resulting in severe PIPN. The aim of this study was to determine the impact of clopidogrel as a risk factor for the development of PIPN, using a retrospective cohort study. Data from paclitaxel-treated patients with or without clopidogrel and low-dose aspirin treatment were retrieved from medical charts. A total of 161 adult patients were included in this study: 135 were controls, 9 were clopidogrel-treated and 17 were aspirin-treated. The clopidogrel group had a greater proportion of males and a higher rate of comorbidities, such as diabetes mellitus and dyslipidemia, than the control group. However, patient characteristics were similar between the clopidogrel and aspirin groups. Severe PIPN was diagnosed in 3 (2.2%) and 2 (22.2%) patients in the control and clopidogrel groups, respectively (odds ratio: 12.0; p = 0.031). No patients in the aspirin group presented with severe neuropathy. These pilot data suggest that concomitant treatment with clopidogrel leads to a greater risk of PIPN. The avoidance of concomitant clopidogrel use may be effective in reducing clopidogrel-associated PIPN.
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; Bennett, David L H
Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes. Almost half of DPN patients develop neuropathic pain 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 neuropathic pain in a deeply phenotyped cohort of patients with DPN. While no rare variants were found in 78 participants with painless DPN, we identified twelve rare Nav1.7 variants in ten (out of 111) study participants with painful DPN. Five of these variants had previously been described in the context of other neuropathic pain disorders and seven have not previously been linked to neuropathic pain. Those patients with rare variants reported more severe pain and greater sensitivity to pressure stimuli on quantitative sensory testing. Electrophysiological characterization of two of the novel variants (M1852T and T1596I) demonstrated gain of function changes as a consequence of markedly impaired channel fast inactivation. By using a structural model of Nav1.7 we were also able provide further insight into the structural mechanisms underlying fast activation and the role of the C-terminal domain in this process. Our observations suggest that rare Nav1.7 variants contribute to the development neuropathic pain in patients with diabetic peripheral neuropathy. Their identification should aid understanding of sensory phenotype, patient stratification and help target treatments effectively.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Fernando, Malindu; Crowther, Robert; Lazzarini, Peter; Sangla, Kunwarjit; Cunningham, Margaret; Buttner, Petra; Golledge, Jonathan
Diabetic peripheral neuropathy is an important cause of foot ulceration and limb loss. This systematic review and meta-analysis investigated the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and dynamic plantar pressures. Electronic databases were searched systematically for articles reporting the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and plantar pressures. Searches were restricted to articles published between January 2000 and April 2012. Outcome measures assessed included spatiotemporal parameters, lower limb kinematics, kinetics, muscle activation and plantar pressure. Meta-analyses were carried out on all outcome measures reported by ≥3 studies. Sixteen studies were included consisting of 382 neuropathy participants, 216 diabetes controls without neuropathy and 207 healthy controls. Meta-analysis was performed on 11 gait variables. A high level of heterogeneity was noted between studies. Meta-analysis results suggested a longer stance time and moderately higher plantar pressures in diabetic peripheral neuropathy patients at the rearfoot, midfoot and forefoot compared to controls. Systematic review of studies suggested potential differences in the biomechanical characteristics (kinematics, kinetics, EMG) of diabetic neuropathy patients. However these findings were inconsistent and limited by small sample sizes. Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies. © 2013.
Biomechanical alterations in diabetes are believed to contribute to plantar neuropathic ulceration. This exploratory study documents clinical measures of flexibility and strength, alongside three-dimensional biomechanical gait data of the lower limb, in 10 patients with a history of neuropathic ulceration (DNU; n=10). Comparative data is presented from age and gender matched groups with; diabetes peripheral neuropathy and no ulcer history (DWN; n=10), diabetes and no peripheral neuropathy (DNN; n=10) and a non-diabetes reference group (NOND; n=10). Biomechanical data were collected at a comfortable walking speed with a Vicon motion analysis system. Clinical measures showed a non-significant trend toward decreased static range of motion at the ankle and first metatarsophalangeal joints, with worsening neuropathy status. Of the diabetes groups, knee and ankle strength was significantly lower in those with an ulcer history (p=0.01-0.03), with the exception of knee extension. In the DNU group, walking speed was on average 0.17 ms slower compared to NOND (p=0.04). The DNU group demonstrated a lower range of motion than NOND at the: hips (frontal plane, by 25%: p=0.03); hips and knees (transverse plane, 31%: p=0.01 and 32%: pgait alterations in people with clinically severe peripheral neuropathy and related plantar foot ulcer history. Further research is needed to explore potential casual pathways. Copyright © 2013 Elsevier B.V. All rights reserved.
Nasiry, Davood; Khalatbary, Ali Reza; Ahmadvand, Hassan; Talebpour Amiri, Fereshteh; Akbari, Esmaeil
Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat. The DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments. Degeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction. Our results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Protection against
Abstract Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4%) had neuropathies remote from procedural sites and 36 patients (54.5%) had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15\\/30) developed following relatively short procedures. In 27% of cases (8\\/30) remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7\\/30: 23.3%), making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12\\/36, 33.3%) accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF) formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation.
Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5).
Kim, Hee-Jin; Sohn, Kwang-Min; Shy, Michael E; Krajewski, Karen M; Hwang, Miok; Park, June-Hee; Jang, Sue-Yon; Won, Hong-Hee; Choi, Byung-Ok; Hong, Sung Hwa; Kim, Byoung-Joon; Suh, Yeon-Lim; Ki, Chang-Seok; Lee, Soo-Youn; Kim, Sun-Hee; Kim, Jong-Won
We have identified missense mutations at conserved amino acids in the PRPS1 gene on Xq22.3 in two families with a syndromic form of inherited peripheral neuropathy, one of Asian and one of European descent. The disease is inherited in an X-linked recessive manner, and the affected male patients invariably develop sensorineural hearing loss of prelingual type followed by gating disturbance and visual loss. The family of European descent was reported in 1967 as having Rosenberg-Chutorian syndrome, and recently a Korean family with the same symptom triad was identified with a novel disease locus CMTX5 on the chromosome band Xq21.32-q24. PRPS1 (phosphoribosyl pyrophosphate synthetase 1) is an isoform of the PRPS gene family and is ubiquitously expressed in human tissues, including cochlea. The enzyme mediates the biochemical step critical for purine metabolism and nucleotide biosynthesis. The mutations identified were E43D, in patients with Rosenberg-Chutorian syndrome, and M115T, in the Korean patients with CMTX5. We also showed decreased enzyme activity in patients with M115T. PRPS1 is the first CMT gene that encodes a metabolic enzyme, shedding a new light on the understanding of peripheral nerve-specific metabolism and also suggesting the potential of PRPS1 as a target for drugs in prevention and treatment of peripheral neuropathy by antimetabolite therapy.
Misra, Stuti L; Craig, Jennifer P; Patel, Dipika V; McGhee, Charles N J; Pradhan, Monika; Ellyett, Kevin; Kilfoyle, Dean; Braatvedt, Geoffrey D
We investigated the relationship between corneal subbasal nerve (SBN) plexus density, corneal sensitivity, and peripheral and cardiac autonomic neuropathy in patients with type 1 diabetes mellitus. We recruited 53 patients with type 1 diabetes mellitus and 40 normal control participants. Corneal in vivo confocal microscopy (IVCM) and sensitivity testing were performed on one eye of each subject. Autonomic function testing was done and an overall neuropathy score obtained from a combination of a symptomatic neuropathy score, clinical assessment, biothesiometry, and nerve conduction tests. The corneal SBN density (P < 0.001) and corneal sensitivity (P < 0.001) were significantly lower in subjects with diabetes compared to controls. A modest negative correlation between total neuropathy score and SBN density was observed (r = -0.33, P = 0.01). A negative correlation between corneal sensitivity and expiration/inspiration component of the autonomic nerve analysis (ANS-EI) also was noted (r = -0.36, P = 0.008). Corneal SBN density was abnormal in 50% of diabetic subjects classified as "Normal" by the clinical and electrophysiological based tests of total neuropathy score. The correlation of corneal SBN density with total neuropathy score suggests that reduced corneal nerve density reflects peripheral neuropathy in diabetes. Corneal SBN changes precede other clinical and electrophysiology tests of neuropathy supporting a possible role for corneal IVCM and corneal sensitivity testing as surrogate markers in the assessment of diabetic peripheral and cardiac autonomic neuropathy.
Ana Claudia de Souza Fortaleza
Full Text Available Diabetic Peripheral Neuropathy (DPN brings on reduced somatosensation, which can lead to changes in postural control. The objective of this study was to evaluate postural control in a standing position and in different conditions, as well as functional balance in individuals with DPN, make the correlation between the results obtained from the postural control assessment with the values from the functional balance test and compare the results obtained in the neuropathy group with those of the control group, checking for possible differences between the evaluation conditions of both groups. The study included 13 women with DPN (NG and 17 non-diabetic women (CG. Postural control assessment was performed by kinemetry in the following conditions: eyes opened (EO, eyes closed (EC, and semi-tandem (ST. The data was processed in MATLAB and the following variables were generated: mean amplitude of oscillation (MAO in the anterior-posterior (AP and medial-lateral (ML direction; and average speed of oscillation (ASO in AP and ML direction. Functional balance was assessed by the Timed Up and Go Test. There was significant difference between the groups (p≤0.005 in MAO-AP EO and EC, MAO-ML EC and ST, and ASO-ML ST. There were differences between the conditions EO and ST (p≤0.005 and EC and ST (p≤0.005 for the variables MAO-ML and ASO-ML with greater damage to the NG, which also had a lower functional balance (p=0.001. ML instability was positively correlated with functional imbalance. The results show a change in the postural control system in the DPN, which could lead these individuals to a higher risk for falls and functional impairment.
Feldman, David S; Ruchelsman, David E; Spencer, Daniel B; Straight, Joseph J; Schweitzer, Mark E; Axelrod, Felicia B
To determine the features of the underlying destructive arthropathy in the peripheral joints of children with hereditary sensory and autonomic neuropathy (HSAN) type III and to compare and contrast this to the arthropathy noted in HSAN type IV, as both groups experience decreased pain perception. From a database of 547 patients with HSAN type III and 32 patients with HSAN type IV, we performed a retrospective chart review and radiographic analysis of all patients who presented with joint swelling and deformity. Underlying joint pathology was classified as either osteonecrosis or Charcot arthropathy. In the HSAN type III population, 44 (8%; 22 males and 22 females) of the 547 patients had clinical evidence of arthropathy. In 42 patients, 48 joints demonstrated radiographic evidence of osteonecrosis; 45 (94%) of the 48 joints with osteonecrosis occurred in the lower extremity. In each case of osteonecrosis of the knee (n = 19), isolated involvement of the lateral distal femoral condyle was seen consisting of varying sizes of posterolateral osteochondral fragmentation. In the 32 patients comprising the HSAN type IV population, 18 (56%) were found to have radiographic findings consistent with Charcot arthropathy in a total of 30 affected joints. One patient demonstrated Charcot arthropathy of the spine and subsequent progressive spondylolisthesis. Nine patients (12 joints) also demonstrated osteomyelitis. In patients with HSAN type III, osteonecrosis is the initial lesion preceding destructive arthropathy. Osteonecrosis and osteochondral fragmentation were always isolated at the lateral distal femoral condyle in the knee. This pathology may be amenable to surgical reconstruction and fixation to stabilize the knee and prevent further degeneration. Hereditary sensory and autonomic neuropathy type IV was most commonly associated with Charcot arthropathy or joint subluxation and dislocation. Late secondary changes at the articular surface may make radiographic distinction
Full Text Available Abstract Prevalence of diabetes mellitus (DM has reached epidemic proportions in Sri Lanka. Presently there are studies on the community prevalence of distal peripheral neuropathy (DPN in Sri Lanka. We describe prevalence, patterns and predictors of DPN in patients with DM in Sri Lanka. Data were collected as part of a national study on DM. In new cases DPN was assessed using the Diabetic-Neuropathy-Symptom (DNS score, while in those with established diabetes both DNS and Toronto-Clinical-Scoring-System (TCSS were used. A binary logistic-regression analysis was performed with ‘presence of DPN’ as the dichomatous dependent variable and other independent co-variants. The study included 528 diabetic patients (191-new cases, with a mean age of 55.0 ± 12.4 years and 37.3% were males, while 18% were from urban areas. Prevalence of DPN according to DNS score among all patients, patients with already established diabetes and newly diagnosed patients were 48.1%, 59.1% and 28.8% respectively. Prevalence of DPN in those with established DM as assessed by TCSS was 24% and the majority had mild DPN (16.6%. The remainder of the abstract is based on subjects with established DM. The prevalence of DPN in males and female was 20.0% and 26.4% respectively. The mean age of those with and without DPN was 62.1 ± 10.8 and 55.1 ± 10.8 years respectively (p
McInnes Alistair D
Full Text Available Abstract Background Amongst the many identified mechanisms leading to diabetic foot ulceration, ill-fitting footwear is one. There is anecdotal evidence that people with diabetic peripheral neuropathy wear shoes that are too small in order to increase the sensation of fit. The aim of this study was to determine whether people with diabetic sensory neuropathy wear appropriate length footwear. Methods A case–control design was used to compare internal shoe length and foot length differences between a group of people with diabetes and peripheral sensory neuropathy and a group of people without diabetes and no peripheral sensory neuropathy. Shoe and foot length measurements were taken using a calibrated Internal Shoe Size Gauge® and a Brannock Device®, respectively. Results Data was collected from 85 participants with diabetes and 118 participants without diabetes. The mean difference between shoe and foot length was not significantly different between the two groups. However, a significant number of participants within both groups had a shoe to foot length difference that lay outside a previously suggested 10 to 15 mm range. From the diabetic and non-diabetic groups 82% (70/85 and 66% (78/118, respectively had a foot to shoe length difference outside this same range. Conclusions This study shows that although there is no significant difference in shoe-length fit between participants with and without neuropathy, a significant proportion of these populations wear shoes that are either too long or too short for their foot length according to the 10 to 15 mm value used for comparison. The study has highlighted the need for standardised approaches when considering the allowance required between foot and internal shoe length and for the measurement and comparison of foot and shoe dimensions.
Fernando, Malindu Eranga; Crowther, Robert George; Pappas, Elise; Lazzarini, Peter Anthony; Cunningham, Margaret; Sangla, Kunwarjit Singh; Buttner, Petra; Golledge, Jonathan
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, pdiabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More homogenous data is needed to confirm these findings.
El Euch-Fayache, Ghada; Bouhlal, Yosr; Amouri, Rim; Feki, Moncef; Hentati, Fayçal
Ataxia with vitamin E deficiency is an autosomal recessive cerebellar ataxia caused by mutations in the α-tocopherol transfer protein coding gene localized on chromosome 8q, leading to lower levels of serum vitamin E. More than 91 patients diagnosed with ataxia with vitamin E deficiency have been reported worldwide. The majority of cases originated in the Mediterranean region, and the 744delA was the most common mutation among the 22 mutants previously described. We examined the clinical and molecular features of a large cohort of 132 Tunisian patients affected with ataxia with vitamin E deficiency. Of these patients, nerve conduction studies were performed on 45, and nerve biopsy was performed on 13. Serum vitamin E was dramatically reduced for 105 of the patients analysed. Molecular analysis revealed that 91.7% of the patients (n = 121) were homozygous for the 744delA mutation. Three other mutations were detected among the remaining patients (8.3%, n = 11) in the homozygous state. Two were previously reported (400C>T and 205-1G>T), and one was novel (553+1T>A). Age of onset was 13.2 ± 5.9 years, with extremes of 2 and 37 years. All described patients exhibited persistent progressive cerebellar ataxia with generally absent tendon reflexes. Deep sensory disturbances, pyramidal syndrome and skeletal deformities were frequent. Head tremor was present in 40% of the patients. Absence of neuropathy or mild peripheral neuropathy was noted in more than half of the cohort. This is the largest study of the genetic, clinical and peripheral neuropathic characteristics in patients with ataxia and vitamin E deficiency. The 744delA mutation represents the most common pathological mutation in Tunisia and worldwide, likely because of a Mediterranean founder effect. Our study led us to suggest that any patient displaying an autosomal recessive cerebellar ataxia phenotype with absent tendon reflexes and minor nerve abnormalities should first be screened for the 744delA mutation
Eckhoff, L; Knoop, A S; Jensen, M-B
,725 patients with early stage breast cancer who randomly were assigned to three cycles of epirubicin and cyclophosphamide followed by three cycles docetaxel (D100) or six cycles of cyclophosphamide and docetaxel (D75). Eligible patients completed chemotherapy, received docetaxel, and provided information......Docetaxel-induced peripheral neuropathy (PN) can lead to sub-optimal treatment in women with early breast cancer. Here, we compare the frequency of dose reduction as a result of PN in two different adjuvant regimens. From the Danish Breast Cancer Cooperative Group READ trial we included 1...... on patient-reported outcome (secondary outcome of trial) including PN. Associations between PN and risk factors were analyzed by multivariate logistic regression. Overall 597 patients (34 %) reported PN, grades 2-4, during treatment, 194 (11 %) after the first cycle [early onset peripheral neuropathy (EPN...
Kumari, Sonia; Sherriff, Jennifer M; Spooner, David; Beckett, Robert
Peripheral neuropathy is a well-recognised side effect of the cholesterol-lowering statins. Red yeast rice (RYR) is a traditional Chinese herb, widely available over-the-counter that has also been found to reduce cholesterol. Little data is available regarding its side effect profile. We report a case of a 60-year-old male receiving therapeutic imatinib for metastatic gastrointestinal tumour (GIST), who developed peripheral neuropathy while also taking RYR. The symptoms completely settled following withdrawal of the RYR and he has subsequently continued to take imatinib for over 2 years with no adverse effects. Further research into the safety profile of RYR is needed. The importance of questioning patients about over the counter medications and herbal remedies cannot be overemphasised.
Ahmed, Marwan A.; Muntingh, George L.; Paul Rheeder
Peripheral neuropathy (PN) is a primary complication of type 2 diabetes mellitus (T2DM) and a direct manifestation of vitamin B12 deficiency. Examining the effects of metformin use on PN status became imperative following clinical studies that showed the vitamin B12-lowering effect of the medication. The complexity of the topic and the inconsistency of the results warrant consideration of topic-specific perspectives for better understanding of the available evidence and more appropriate desig...
Ahmed, Marwan A; Muntingh, George L; Rheeder, Paul
Peripheral neuropathy (PN) is a primary complication of type 2 diabetes mellitus (T2DM) and a direct manifestation of vitamin B12 deficiency. Examining the effects of metformin use on PN status became imperative following clinical studies that showed the vitamin B12-lowering effect of the medication. The complexity of the topic and the inconsistency of the results warrant consideration of topic-specific perspectives for better understanding of the available evidence and more appropriate design of future studies.
Ahmed, Marwan A.; Muntingh, George; Rheeder, Paul
Background 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 ...
Full Text Available Objective: To study the effect of Xueshuantong combined with antioxidant drugs on nerve conduction function and oxidative stress in patients with diabetic peripheral neuropathy. Methods: 138 cases of patients with diabetic peripheral neuropathy who were treated in endocrinology department of our hospital between June 2014 and October 2016 were enrolled and randomly divided into two groups. The combination group received Xueshuantong combined with antioxidant drug therapy, and the control group received antioxidant drug therapy. Before and after treatment, the nerve conduction velocity as well as serum content of oxidative stress indexes and nerve cytokines was measured. Results: 4 weeks and 8 weeks after treatment, common peroneal nerve and median nerve MNCV and SNCV as well as serum SOD, GSH-Px, HO-1, CAT, CNTF, BDNF and SDF-1α levels of both groups were significantly higher than those before treatment while serum MDA, AOPP and 8-OHdG levels were significantly lower than those before treatment, and common peroneal nerve and median nerve MNCV and SNCV as well as serum SOD, GSH-Px, HO-1, CAT, CNTF, BDNF and SDF-1α levels of combination group were significantly higher than those of control group while serum MDA, AOPP and 8-OHdG levels were significantly lower than those of control group. Conclusion: Xueshuantong combined with antioxidant drugs can improve the nerve conduction function, inhibit oxidative stress response and improve neurotrophy status in patients with diabetic peripheral neuropathy.
Chatchawan, Uraiwan; Eungpinichpong, Wichai; Plandee, Piyawan; Yamauchi, Junichiro
BACKGROUND Peripheral neuropathy is the most common complications of diabetic patients and leads to loss of plantar cutaneous sensation, movement perception, and body balance. Thai foot massage is an alternative therapy to improve balance. Therefore, the purpose of this study was to investigate the effects of Thai foot massage on balance performance in diabetic patients with peripheral neuropathy. MATERIAL AND METHODS Sixty patients with type-2 diabetes were recruited and randomly assigned into either the Thai foot massage or control groups. The Thai foot massage group received a modified Thai traditional foot massage for 30 min, 3 days per week for 2 weeks. We measured timed up and go (TUG), one leg stance: OLS), the range of motion (ROM) of the foot, and foot sensation (SWMT) before treatment, after the first single session, and after the 2-week treatment. RESULTS After the single treatment session, only the Thai foot massage group showed a significant improvement in TUG. After the 2-week treatment, both Thai foot massage and control groups showed a significant improvement of TUG and OLS (Pfoot massage group showed better improvement in TUG than the control group (pfoot massage group also showed significant improvements in ROM and SWMT after the 2-week treatment. CONCLUSIONS The results of this study suggest that Thai foot massage is a viable alternative treatment for balance performance, ROM of the foot, and the foot sensation in diabetic patients with peripheral neuropathy.
Chatchawan, Uraiwan; Eungpinichpong, Wichai; Plandee, Piyawan; Yamauchi, Junichiro
Background Peripheral neuropathy is the most common complications of diabetic patients and leads to loss of plantar cutaneous sensation, movement perception, and body balance. Thai foot massage is an alternative therapy to improve balance. Therefore, the purpose of this study was to investigate the effects of Thai foot massage on balance performance in diabetic patients with peripheral neuropathy. Material/Methods Sixty patients with type-2 diabetes were recruited and randomly assigned into either the Thai foot massage or control groups. The Thai foot massage group received a modified Thai traditional foot massage for 30 min, 3 days per week for 2 weeks. We measured timed up and go (TUG), one leg stance: OLS), the range of motion (ROM) of the foot, and foot sensation (SWMT) before treatment, after the first single session, and after the 2-week treatment. Results After the single treatment session, only the Thai foot massage group showed a significant improvement in TUG. After the 2-week treatment, both Thai foot massage and control groups showed a significant improvement of TUG and OLS (Pmassage group showed better improvement in TUG than the control group (pmassage group also showed significant improvements in ROM and SWMT after the 2-week treatment. Conclusions The results of this study suggest that Thai foot massage is a viable alternative treatment for balance performance, ROM of the foot, and the foot sensation in diabetic patients with peripheral neuropathy. PMID:25892354
Full Text Available Hepatitis C virus (HCV is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy, cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week and ribavirin (500 mg orally, twice a day for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.
Patil, Pravinkumar R; Wolfe, Jonathan; Said, Qayyim; Thomas, Jeremy; Martin, Bradley C
To examine the proportion of diabetic peripheral neuropathy (DPN) patients receiving pharmacologic DPN treatments and specifically to identify the rates and factors associated with opioid use and first-line opioid use. A 10% sample of IMS-LifeLink claims data from 1998 through 2008 was used. The study population consisted of diabetic patients who met DPN criteria using a validated DPN algorithm. Multivariable logistic regression controlling for demographics, comorbidities, and other clinical characteristics was used to identify factors associated with any DPN pharmacologic treatment, any opioid use, and first-line opioid treatment. Sensitivity analyses were conducted to explore variations in exclusion criteria as well as opioid use definitions. A total of 666 DPN patients met inclusion criteria and pharmacologic treatment was received by 288 patients (43.24%) and of those, 154 (53.47%) had DPN-related opioid use and 96 (33.33%) received opioid as first-line treatment. Persons with diabetic complications were more likely to use opioids (odds ratio=4.53; 95% confidence interval, 1.09-18.92). Food and Drug Administration-approved DPN agents duloxetine 1.04% (n=3) and pregabalin 5.56% (n=16) had much lower rates of use. DPN-related drug use and DPN-related opioid usage increased as we used less restrictive samples in sensitivity analyses. Opioids were the most frequently prescribed first-line agents for DPN. More than 50% of DPN patients remained untreated with pharmacologic agents 1 year after a DPN diagnosis.
Hou, Yu; Liu, Sha; Zhu, Tingting; Zhang, Huan; Liu, Gang; Zhu, Yan; Chen, Huiling
To evaluate the diagnostic value of vibration perception threshold (VPT) in diabetic peripheral neuropathy (DPN) by the receiver operating characteristic curve (ROC) and to establish its cut-off threshold. All patients had the VPT examination and nerve conduction velocity (NCV) examination. NCV examination showed that 283 patients with Type 2 diabetes were divided into a DPN group (n=151) and an NDPN group (n=132). The VPT diagnosis was evaluated by Youden index, sensitivity, specificity and the area under ROC curve. The best cut-off threshold was defined by the Youden index. 1) The NCV was significantly slower, while the VPT was higher in the DPN group than those in the NDPN group (both P values <0.05). 2) The VPT and NCV of both sides of the limb had no difference in all patients. 3) With NCV as the golden diagnosis criterion, the area under ROC of VPT was 0.707, the best cut-off threshold was 10.54 V, the sensitivity was 0.596, the specificity was 0.848, and the Youden index was 0.445. 4) The diagnosis ratio of NCV combined with VPT was 60.4%, significantly higher than that of NCV alone (P<0.05). Compared with NCV examination, VPT has good diagnostic value for DPN. The best cut-off value is 10.54 V.
Full Text Available The rat sciatic nerve has attracted widespread attention as an excellent model system for studying autophagy alterations in peripheral neuropathies. In our laboratory, we have developed an original rat model, which we used currently in routine novel drug screening and to evaluate treatment strategies for chronic inflammatory demyelinating polyneuropathy (CIDP and other closely related diseases. Lewis rats injected with the S-palmitoylated P0(180-199 peptide develop a chronic, sometimes relapsing-remitting type of disease. Our model fulfills electrophysiological criteria of demyelination with axonal degeneration, confirmed by immunohistopathology and several typical features of CIDP. We have set up a series of techniques that led us to examine the failures of autophagy pathways in the sciatic nerve of these model rats and to follow the possible improvement of these defects after treatment. Based on these newly introduced methods, a novel area of investigation is now open and will allow us to more thoroughly examine important features of certain autophagy pathways occurring in sciatic nerves.
Full Text Available Purpose. The aim of this present study was to investigate the ground reaction forces (GRFs alterations in stroke survivors with diabetic peripheral neuropathy (DPN. Methods. Ten stroke survivors with DPN, 10 stroke survivors without DPN, and 10 healthy controls with matched body weight between groups participated in this case-control cross-sectional study. Three-dimensional GRFs (anterior-posterior, medial-lateral, and vertical were collected at a comfortable walking speed using the Nexus Vicon motion analysis system and force plate. The Kruskal–Wallis test was used to analyze GRFs parameters. Results. We found significant alterations of medial-lateral forces of the nonparetic side and vertical forces of the paretic side in stroke survivors with DPN compared to stroke survivors without DPN and healthy controls. In addition, there were smaller braking and lower propulsion peak in anterior-posterior forces, smaller magnitude of medial-lateral forces, and lower first and second peak of vertical forces in stroke survivors with DPN compared to stroke survivors without DPN and healthy controls. Conclusion. The study findings identified that GRFs were affected in stroke survivors with DPN on both the paretic and the nonparetic sides. Further investigations are warranted to explore the impact of DPN on the kinematics and muscle activity related to the gait performance in stroke survivors with DPN.
Kumar, Shaji K; Laubach, Jacob P; Giove, Thomas J; Quick, Maureen; Neuwirth, Rachel; Yung, Godwin; Rajkumar, S Vincent; Richardson, Paul G
Peripheral neuropathy (PN) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib-induced PN (BiPN) and it has been hypothesized that reducing inflammation with concomitant dexamethasone may reduce BiPN incidence and/or severity. We retrospectively analysed PN rates from 32 studies (2697 patients with previously untreated multiple myeloma) incorporating bortezomib and differing dexamethasone schedules: partnered dosing (days of and after bortezomib), weekly dosing, and other dosing schedules (e.g. days 1-4, 8-11). Pooled overall PN rates were 45·5%, 63·9%, and 47·5%, respectively, with 5·3%, 11·0%, and 9·6% grade ≥3. Adjusting for potential confounders (age, gender, presence of thalidomide, bortezomib treatment duration), PN rates in patients on partnered dosing schedules appeared lower than in patients on weekly or other dosing schedules. Analyses conducted using patient-level data suggest that cumulative dexamethasone dose, a potential confounding factor, is unlikely to have influenced the analyses. Findings were similar in a separate pooled analysis excluding data from regimens incorporating thalidomide, when pooled overall PN rates were 50·1%, 63·9%, and 48·3%, respectively, with 4·2%, 11·0%, and 8·6% grade ≥3. These findings suggest that partnered dexamethasone dosing may result in less severe BiPN compared with alternative dexamethasone dosing schedules. © 2017 John Wiley & Sons Ltd.
Alleman, Cathelijne J M; Westerhout, Kirsten Y; Hensen, Marja; Chambers, Colette; Stoker, Malcolm; Long, Stephen; van Nooten, Floortje E
Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes mellitus. A systematic literature review was conducted to provide an overview of published literature in the last 10-years on the epidemiology, humanistic burden and economic burden of PDPN in Europe. A search was performed according to pre-defined strategy and review criteria in Embase, Pubmed, and conference proceedings databases from 2003 till December 2012. In total, 30 publications written in English covering the relevant patient population and topics of interest. European prevalence ranges from 6% to 34% in diabetes mellitus patients. PDPN has a significant humanistic and economic impact. Patients are limited in their general functioning and their ability to sleep and often experience anxiety and depression. Not surprisingly, PDPN is associated with reduced Health-Related-Quality-of-Life (HRQoL). PDPN patients incur high health care costs due to hospitalizations and outpatient visits. In addition, the painful symptoms cause impaired work productivity. Studies suggest both humanistic and economic burden increase with higher pain severity. The burden from PDPN appears to be higher with increasing pain severity. More severe pain leads to a higher impairment in daily functioning, sleep and HRQoL. Higher pain intensity also leads to increasing healthcare costs and work productivity losses. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Streckmann, Fiona; Balke, Maryam; Lehmann, Helmar C; Rustler, Vanessa; Koliamitra, Christina; Elter, Thomas; Hallek, Michael; Leitzmann, Michael; Steinmetz, Tilman; Heinen, Petra; Baumann, Freerk T; Bloch, Wilhelm
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and clinically relevant side effect of chemotherapy. Approximately 50% of all leukemia, lymphoma, colorectal- and breast cancer patients are affected. CIPN is induced by neurotoxic chemotherapeutic agents and can manifest with sensory and/or motor deficits. It is associated with significant disability and poor recovery. Common symptoms include pain, altered sensation, reduced or absent reflexes, muscle weakness, reduced balance control and insecure gait. These symptoms not only affect activities of daily living, subsequently reducing patients' quality of life, they have far more become a decisive limiting factor for medical therapy, causing treatment delays, dose reductions, or even discontinuation of therapy, which can affect the outcome and compromise survival. To date, CIPN cannot be prevented and its occurrence presents a diagnostic dilemma since approved and effective treatment options are lacking. Promising results have recently been achieved with exercise. We have revealed that sensorimotor training (SMT) or whole body vibration (WBV) can reduce the symptoms of CIPN and attenuate motor and sensory deficits. We furthermore detected a tendency that it may also have a preventive effect on the onset of CIPN. We are therefore conducting a prospective, multicentre, controlled clinical trial involving 236 oncological patients receiving either oxaliplatin (N = 118) or vinca-alkaloid (N = 118) who are randomized to one of two interventions (SMT or WBV) or a treatment as usual (TAU) group. Primary endpoint is the time to incidence of neurologically confirmed CIPN. Secondary endpoints are pain, maintenance of the functionality of sensory as well as motor nerve fibres as well as the level of physical activity. The baseline assessment is performed prior to the first cycle of chemotherapy. Subsequent follow-up assessments are conducted at 12 weeks, after completion of chemotherapy, and at a 3-month
Full Text Available Abstract Background Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. Methods This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN. Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score". Results Twenty one patients (70% of the group taking omega-3 fatty acid supplement (n = 30 did not develop PN while it was 40.7%( 11 patients in the placebo group(n = 27. A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88, p = 0.029. There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (−2.06 -0.02, p = 0.054. Conclusions Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients’ quality of life. Trial registration This trial was registered at ClinicalTrials.gov (NCT01049295
Full Text Available Gavin Taylor-Stokes1, James Pike1, Alesia Sadosky2, Arthi Chandran2, Thomas Toelle31Adelphi Real World, Adelphi Mill, Bollington, Macclesfield, Cheshire, UK; 2Pfizer Inc, New York, NY, USA; 3Department of Neurology, Technische Universität München, Munich, GermanyObjective: To evaluate the association of patient-reported severity of painful diabetic peripheral neuropathy (pDPN with other outcomes in a European population of patients using the Adelphi Disease Specific Programme for pDPN (DSP III, 2008.Methods: The severity of patients' pDPN (mild, moderate, or severe was rated independently by both patients and physicians. Relationships were evaluated between patient-reported pDPN severity and other patient-reported outcomes including pain, sleep, function, and work productivity. Physicians rated the severity of patients’ pDPN (1 = mild, 2 = moderate, 3 = severe and sleep interference.Results: Patient-reported data were available from 634 individuals (56.2% male, mean age 63 years from France, Germany, Italy, and the UK, of whom only 22.2% reported that they were currently employed. pDPN severity was rated as mild, moderate, and severe by 22.2%, 60.9%, and 16.9% of the patients, respectively. There was a significant association between patient-rated and physician-rated pDPN severity (P < 0.0001, although there were discrepancies in agreement (kappa = 0.37, 95% confidence interval [CI] 0.31, 0.43; weighted kappa = 0.43, 95% CI 0.37, 0.48 among physician and patient ratings in a substantial proportion of patients across severity categories. Higher pDPN severity was associated with greater interference of daily function including sleep (P < 0.0001 for all pairwise comparisons. Among employed patients, percent of pDPN-related impairment while at work (presenteeism and overall work impairment increased with greater pDPN severity, resulting in indirect costs that increased significantly with pDPN severity; $8266, $15,449, and $24,300 for mild
Yazla, Semih; Özmen, Süay; Kıyıcı, Sinem; Yıldız, Demet; Haksever, Mehmet; Gencay, Sündüz
Olfaction and gustation in patients with diabetes mellitus have great significance on quality of life, and their impairment may result in possible hazards. A limited number of studies have been performed to determine the alteration of both gustatory and olfactory function in type 2 diabetic patients with diabetic peripheral neuropathy (DPN). The aim of this study was to determine whether type 2 diabetic patients, with and without DPN, exhibit major olfactory and gustatory dysfunction using validated and dependable techniques. An observational-analytical case-control study was conducted. Sixty patients with type 2 diabetes mellitus (T2DM) and 30 healthy control subjects with a mean age of 57.1 ± 8.4 were included in the study. Patients with T2DM were recruited from the endocrinology outpatient clinic. After clinical evaluation and electromyography examination, patients with T2DM were divided into the 2 groups, with and without DPN. After a 10-hour fasting period, blood samples were taken for the measurement of serum creatinine, lipids, and HbA1c. For the quantitative assessment of olfactory function, all participants underwent butanol threshold test and odour identification test. Gustatory function was tested administering a whole-mouth above-threshold test using sucrose solutions. The control subjects showed significantly higher Sniffin' sticks and butanol threshold scores than the diabetic patients without DPN (P = .001 and P = .009). No significant difference was found in the gustatory function test between these 2 groups (P = .116). Diabetic patients with DPN had lower Sniffin' sticks scores, butanol threshold scores, and higher sucrose thresholds compared to the controls (P diabetic patients with or without DPN regarding Sniffin' sticks scores, butanol threshold, and sucrose thresholds (P = .302, P = .181, and P = .118). In conclusion, this study demonstrates that T2DM is associated with olfactory and gustatory dysfunction. The fact that there
Mei, Jun-hua; Wang, Jun-il; Luo, Li-jun; Chen, Guo-hua; Zhang, Zhong-wen; Pan, Xiao-feng; Wei, Dan; Shao, Wei
To observe the effects of acupuncture on neurofunction and neuropsychological factors of chronic alcoholic peripheral neuropathy (CAPN) patients. Totally 120 CAPN patients were assigned to the common treatment group, acupuncture group A, and acupuncture group B according to random digit table, 40 in each group. All patients recieved conventional drug therapy. Besides, patients in the acupuncture group A were additionally needled at Pishu (BL20), Weishu (BL21), Xuehai (SP10), Yinlingquan (SP9), Zusanli (ST36), Yanglingquan (GB34), Jiexi (ST41), Xuanzhong (GB39), Xiangu (ST43),Taixi (KI3), Quchi (LI11), Waiguan (SJ5), Hegu (LI4), and so on. On these bases patients in the acupuncture group B were needled at Sishencong (EX-HN1), Yintang (EX-HN3), Neiguan (PC6), Taichong (LR3), Sanyinjiao (SP6), and Taiyang (EX-HN5). Acupuncture was performed once a day, 14 times as a course; and then once on every other day, 14 times in total for 4 weeks. All treatment lasted for 8 successive weeks. Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Neurological Severity Score (NSS), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA) were assessed, motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) were detected before and after treatment. After 8 weeks of treatment the scores of NIS-LL and NSS significantly decreased in the 3 groups, with statistical difference as compared with before treatment (P acupuncture groups A and B than in the common treatment group (P acupuncture group B (P acupuncture treatment group A and B after 8-week treatment (P acupuncture treatment groups A and B after treatment (P acupuncture treatment group A than in acupuncture treatment group B (P acupuncture groups A and B, with statistical difference as compared with before treatment (P acupuncture treatment group B than in acupuncture treatment group A (P Acupuncture therapy could effectively improve the neurofunction of CAPN patients, and improve
Barton, Al; McLean, B
A 74-year-old woman presented to the neurology clinic with worsening of her longstanding peripheral neuropathy of unknown cause. There was below knee loss of spinothalamic sensation, reduced joint position of toes, absent below hips vibration sensation and absent ankle jerks. Neurophysiology studies showed further progression of her axonal sensory neuropathy. Urine and blood analysis previously carried out in Australia suggested elevated levels of arsenic. After abstinence from seafood, a random urine sample was collected and this confirmed the elevation in urine arsenic (622.1 nmol/L, reference range arsenic. On questioning the patient admitted to taking fish oils, omega-3 oils and glucosamine sulphate dietary supplements in excess of the recommended dosage. These supplements were identified as possible sources of arsenic and the patient was asked to stop all supplements. One month later the urine arsenic had reduced to 57.5 nmol/L. There was an improvement in patient wellbeing, she no longer required Gabapentin for pain relief and the neurophysiology studies also showed improvement. Clinicians should consider heavy metal toxicity as a cause of peripheral neuropathy of unknown cause. A detailed patient history including all dietary supplements is essential to help elucidate the source of heavy metal toxicity.
We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them.
Kisozi, Twaha; Mutebi, Edris; Kisekka, Musubire; Lhatoo, Samden; Sajatovic, Martha; Kaddumukasa, Mark; Nakwagala, Fredrick Nelson; Katabira, Elly
To determine the prevalence and associated risk factors of diabetic peripheral neuropathy (DPN) among newly diagnosed diabetes mellitus patients in Mulago Hospital. A cross-sectional study was conducted among 248 newly diagnosed adult diabetic patients. Using the standard Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) criteria, we screened them for neuropathy. Data on the socio-demographics, age, duration of symptoms and history of diabetic ulcer were analyzed using a multiple logistic regression. A p-value neuropathy and only five percent had severe neuropathy. Age above 60 years was significantly associated with the presence of DPN; (OR 3.72; 95% CI 1.25 - 11.03; p=0.018). The history of ever having a foot ulcer was significantly associated with peripheral neuropathy (OR 2.59; 95% CI: 1.03 - 6.49, p = 0.042). DPN occurs in 1 in 4 of newly diagnosed diabetic patients in Mulago hospital. Two thirds of these patients had moderate to severe neuropathy. DPN was independently associated with increasing age. Early diagnosis of diabetes mellitus, increased diabetes knowledge and regular blood sugar screenings would play an important role in identifying this problem.
Full Text Available BACKGROUND: The absence of a suitable cellular model is a major obstacle for the study of peripheral neuropathies. Human embryonic stem cells hold the potential to be differentiated into peripheral neurons which makes them a suitable candidate for this purpose. However, so far the potential of hESC to differentiate into derivatives of the peripheral nervous system (PNS was not investigated enough and in particular, the few trials conducted resulted in low yields of PNS neurons. Here we describe a novel hESC differentiation method to produce enriched populations of PNS mature neurons. By plating 8 weeks hESC derived neural progenitors (hESC-NPs on laminin for two weeks in a defined medium, we demonstrate that over 70% of the resulting neurons express PNS markers and 30% of these cells are sensory neurons. METHODS/FINDINGS: Our method shows that the hNPs express neuronal crest lineage markers in a temporal manner, and by plating 8 weeks hESC-NPs into laminin coated dishes these hNPs were promoted to differentiate and give rise to homogeneous PNS neuronal populations, expressing several PNS lineage-specific markers. Importantly, these cultures produced functional neurons with electrophysiological activities typical of mature neurons. Moreover, supporting this physiological capacity implantation of 8 weeks old hESC-NPs into the neural tube of chick embryos also produced human neurons expressing specific PNS markers in vivo in just a few days. Having the enriched PNS differentiation system in hand, we show for the first time in human PNS neurons the expression of IKAP/hELP1 protein, where a splicing mutation on the gene encoding this protein causes the peripheral neuropathy Familial Dysautonomia. CONCLUSIONS/SIGNIFICANCE: We conclude that this differentiation system to produce high numbers of human PNS neurons will be useful for studying PNS related neuropathies and for developing future drug screening applications for these diseases.
Yuulia Vladimirovna Karakulova
Full Text Available The indicators of pain and psychological status, the concentrations of serum serotonin and blood platelets, and the levels of brain-derived neurotrophic factor (BDNF and nerve growth factor were studied in 82 patients with diabetic peripheral neuropathy (DPN. Along with conventional treatment aimed to normalize carbohydrate metabolism, 30 patients with DPN received actovegin in an intravenous, jetwise dose of 10.0 ml for 10 days. Prior to treatment, their pain intensity was 5.94±1.2 and 29.6±6.24 scores according to a visual analogue scale (VAS and PainDETECT, respectively. The subclinical level of anxiety and depression was noted. The amount of serotonin in the serum (90.39±55.43 ng/ml and blood platelets (298.13±80.33 ng/ml was lower than that in the control. The content of serum BDNF in DPN was also substantially lower (419.27±132.7 pg/ml; p<0.04 than that in the control. After treatment, the actovegin group showed a more significant reduction in pain syndrome according to the VAS (3.5±0.6 cm; p=0.005 and PainDETECT (19.4±4.1 scores, p=0.005, a decrease in the degree of anxiety and depression according to the Beck inventory (11.4±1.4 scores; p=0.001, and an increase in BDNF levels up to 979.71±289.9 pg/ml. Serum serotonin and blood platelets increased up to 206.13±78.3 and 477.06±114.45 ng/ml, respectively; which is indicative of the correct choice of the treatment for DPN.
Selvarajah, Dinesh; Cash, Tom; Davies, Jennifer; Sankar, Adithya; Rao, Ganesh; Grieg, Marni; Pallai, Shillo; Gandhi, Rajiv; Wilkinson, Iain D.; Tesfaye, Solomon
Clinical methods of detecting diabetic peripheral neuropathy (DPN) are not objective and reproducible. We therefore evaluated if SUDOSCAN, a new method developed to provide a quick, non-invasive and quantitative assessment of sudomotor function can reliably screen for DPN. 70 subjects (45 with type 1 diabetes and 25 healthy volunteers [HV]) underwent detailed assessments including clinical, neurophysiological and 5 standard cardiovascular reflex tests (CARTs). Using the American Academy of Neurology criteria subjects were classified into DPN and No-DPN groups. Based on CARTs subjects were also divided into CAN, subclinical-CAN and no-CAN. Sudomotor function was assessed with measurement of hand and foot Electrochemical Skin Conductance (ESC) and calculation of the CAN risk score. Foot ESC (μS) was significantly lower in subjects with DPN [n = 24; 53.5(25.1)] compared to the No-DPN [77.0(7.9)] and HV [77.1(14.3)] groups (ANCOVA p<0.001). Sensitivity and specificity of foot ESC for classifying DPN were 87.5% and 76.2%, respectively. The area under the ROC curve (AUC) was 0.85. Subjects with CAN had significantly lower foot [55.0(28.2)] and hand [53.5(19.6)] ESC compared to No-CAN [foot ESC, 72.1(12.2); hand ESC 64.9(14.4)] and HV groups (ANCOVA p<0.001 and 0.001, respectively). ROC analysis of CAN risk score to correctly classify CAN revealed a sensitivity of 65.0% and specificity of 80.0%. AUC was 0.75. Both foot and hand ESC demonstrated strong correlation with individual parameters and composite scores of nerve conduction and CAN. SUDOSCAN, a non-invasive and quick test, could be used as an objective screening test for DPN in busy diabetic clinics, insuring adherence to current recommendation of annual assessments for all diabetic patients that remains unfulfilled. PMID:26457582
DiLiberto, Frank E; Tome, Josh; Baumhauer, Judith F; Quinn, Jill R; Houck, Jeff; Nawoczenski, Deborah A
Neuropathic tissue changes can alter muscle function and are a primary reason for foot pathologies in people with Diabetes Mellitus and peripheral neuropathy (DMPN). Understanding of foot kinetics in people with DMPN is derived from single-segment foot modeling approaches. This approach, however, does not provide insight into midfoot power and work. Gaining an understanding of midfoot kinetics in people with DMPN prior to deformity or ulceration may help link foot biomechanics to anticipated pathologies in the midfoot and forefoot. The purpose of this study was to evaluate midfoot (MF) and rearfoot (RF) power and work in people with DMPN and a healthy matched control group. Thirty people participated (15 DMPN and 15 Controls). An electro-magnetic tracking system and force plate were used to record multi-segment foot kinematics and ground reaction forces during walking. MF and RF power, work, and negative work ratios were calculated and compared between groups. Findings demonstrated that the DMPN group had greater negative peak power and reduced positive peak power at the MF and RF (all p≤0.05). DMPN group negative work ratios were also greater at the MF and RF [Mean difference MF: 9.9%; p=0.24 and RF: 18.8%; ppeople with DMPN, the greater proportion of negative work may negatively affect foot structures during forward propulsion, when positive work and foot stability should predominate. Further study is recommended to determine how both MF and RF kinetics influence the development of deformity and ulceration in people with DMPN. Copyright © 2015 Elsevier Ltd. All rights reserved.
Billinger, Sandra A; Sisante, Jason-Flor V; Alqahtani, Abdulfattah S; Pasnoor, Mamatha; Kluding, Patricia M
Aerobic exercise improves vascular endothelial function in people with Type 2 diabetes mellitus (T2DM). There is minimal information available regarding vascular health in people with T2DM and diabetic peripheral neuropathy (DPN). Thus, the primary aim of this secondary analysis was to determine whether a 16-week aerobic exercise intervention could improve vascular health in people with T2DM and DPN. A secondary aim was to explore the relationship between changes in flow-mediated dilation (FMD) and the number of years since diagnosis of DPN. We examined whether a 16-week aerobic exercise intervention would improve vascular health in people with T2DM and DPN. We used Doppler ultrasound to assess brachial artery diameter and peak shear at baseline and post-exercise. Paired t-tests were used to determine whether the outcome measures improved from baseline to post-intervention. Pearson correlation assessed the relationship between DPN (years) and the percent change score (pre- to post-intervention) for FMD. Seventeen individuals were included in the data analysis. After the intervention, peak diameter increased (3.9 (0.5) to 4.0 (0.5) mm; p = 0.07). Time to peak shear occurred at 60.5 (24.6) seconds when compared to baseline at 68.2 (22.7) seconds; p = 0.17. We found that a longer duration (in years) of DPN demonstrated a fair, negative relationship (r = -0.41, p = 0.19) with the percent change in FMD. Aerobic exercise was beneficial for improving measures of vascular health but these were not statistically significant. The magnitude of change may be affected by the duration of DPN.
Full Text Available Diabetic foot ulcers remain one of the most serious complications of diabetes. Peak plantar pressure (PPP and peak pressure gradient (PPG during walking have been shown to be associated with the development of diabetic foot ulcers. To gain further insight into the mechanical etiology of diabetic foot ulcers, examination of the pressure gradient angle (PGA has been recently proposed. The PGA quantifies directional variation or orientation of the pressure gradient during walking, and provides a measure of whether pressure gradient patterns are concentrated or dispersed along the plantar surface. We hypothesized that diabetics at risk of foot ulceration would have smaller PGA in key plantar regions, suggesting less movement of the pressure gradient over time. A total of 27 participants were studied, including 19 diabetics with peripheral neuropathy and 8 non-diabetic control subjects. A foot pressure measurement system was used to measure plantar pressures during walking. PPP, PPG and PGA were calculated for four foot regions - 1st toe (T1, 1st metatarsal head (M1, 2nd metatarsal head (M2, and heel (HL. Consistent with prior studies, PPP and PPG were significantly larger in the diabetic group compared to non-diabetic controls in the T1 and M1 regions, but not M2 or HL. For example, PPP was 165% (P=0.02 and PPG was 214% (P<0.001 larger in T1. PGA was found to be significantly smaller in the diabetic group in T1 (46%, P=0.04, suggesting a more concentrated pressure gradient pattern under the toe. The proposed PGA may improve our understanding of the role of pressure gradient on the risk of diabetic foot ulcers.
Full Text Available The most common causes for surgical procedures involving peripheral nerves are injuries and carpal tunnel syndrome. Carpal tunnel decompression surgery consists in cutting the transverse carpal ligament thereby releasing the nerve entrapped by this ligament. Following the procedure, pain symptoms should subside immediately. If the patient complains about pain that does not subside with time, it is necessary to conduct a diagnostic process. Until recently, electrophysiological tests, which determine the ability to conduct impulses, have been the gold standard. In the recent years, however, ultrasound examinations with the use of high-frequency transducers, which precisely specify the cause of postoperative complications, have been used more and more often as the first choice examination. Such an examination also enables assessment of the adjacent tissues which may be the source of persisting symptoms. This facilitates designing proper treatment. In the case of posttraumatic changes in the nerves, the neurological status (the return of sensation and motor function of the muscles innervated by a given nerve trunk depends on the time from the procedure since nerve tissue regenerates gradually. If the healing process is incorrect, “a neuroma-in-continuity” may form when the regenerate does not penetrate to the peripheral stump and forms a chaotic scar at the reconstruction level. An ultrasound examination enables assessment of the nerve suturing site in terms of nerve trunk continuity restoration, identification of neuromas and control of their growth. Moreover, it enables adhesions to be diagnosed. Based on the interview, clinical examination as well as neurophysiological and ultrasound examinations in posttraumatic or postoperative neuropathies, one can precisely plan the management, i.e. decide whether a wait-and-see attitude should be assumed or a surgical procedure should be conducted as soon as
Doppler, K; Reiners, K
Diabetic neuropathy is a common complication of diabetes mellitus. The length-dependent symmetrical sensorimotor type of neuropathy is the most prevalent form of diabetic neuropathy but other forms of diabetic neuropathy also need to be kept in mind. Their differential diagnosis is often more challenging but implicates specific forms of treatment other than improvement of metabolic control. This article gives an overview of the less frequent forms of diabetic neuropathy and discusses their impact, diagnostic and therapeutic implications. Autonomic diabetic neuropathy, diabetic small fiber neuropathy and less frequent forms of diabetic neuropathy, such as diabetic radiculoplexopathy, diabetic neuropathy of cranial nerves, therapy-induced neuropathy and alternative causes of peripheral neuropathy in patients with diabetes are described. Diagnosis of less frequent subtypes of diabetic neuropathy and differentiation towards alternative causes of peripheral neuropathy are often difficult in daily medical routine. Diagnostic clues are helpful in identifying rarer forms of diabetic neuropathy, thus enabling more specific treatment.
Wozniak, Krystyna M; Wu, Ying; Vornov, James J; Lapidus, Rena; Rais, Rana; Rojas, Camilo; Tsukamoto, Takashi; Slusher, Barbara S
Peripheral neuropathy from nerve trauma is a significant problem in the human population and often constitutes a dose-limiting toxicity in patients receiving chemotherapy. (3-2-Mercaptoethyl)biphenyl-2,3-dicarboxylic acid (E2072) is a potent (K(i) = 10 nM), selective, and orally available inhibitor of glutamate carboxypeptidase II (GCPII). Here, we report that E2072 attenuates hyperalgesia and nerve conduction velocity deficits in preclinical rodent models of neuropathic pain and oxaliplatin-induced neuropathy. In the chronic constrictive injury model, orally administered E2072 reversed pre-existing thermal hyperalgesia in rats in a dose-dependent fashion with a minimally effective dose of 0.1 mg/kg/day. It is noteworthy that multiple days of dosing of E2072 were required before analgesia was realized even though GCPII inhibitory exposures were achieved on the first day of dosing. In addition, analgesia was found to persist for up to 7 days after cessation of dosing, consistent with E2072's pharmacokinetic profile and sustained exposure. Furthermore, in a chronic oxaliplatin-induced neuropathy model (6 mg/kg i.p. oxaliplatin twice weekly for 4 weeks), female BALB/c mice receiving daily oral E2072 at 1.0 and 0.1 mg/kg displayed no deficits in either caudal or digital velocity compared with significant deficits observed in mice treated with oxaliplatin alone (12 ± 3 and 9 ± 2%, respectively). Similar findings were seen with oxaliplatin-induced digital and caudal amplitude deficits. It is noteworthy that E2072 showed no interference with the antineoplastic efficacy of oxaliplatin in mice bearing leukemia (L1210), even at doses 100 times its neuroprotective/analgesic dose, indicating a selective effect on neuropathy. These data support the therapeutic utility of GCPII inhibitors in neuropathy and neuropathic pain.
Full Text Available Background: Diabetes mellitus (DM is a common metabolic disorder that can cause various complications including, peripheral neuropathy (PNP. Some possible risk-factors such as blood glucose level, hyperglycemia, duration of diabetes, and lipid profiles are assumed to be important in diabetic PNP incidence. The aim of this study is to evaluate the prevalence and possible risk-factors of PNP in children with insulin dependent DM. Materials and Methods: Among diabetic children, 146 patients (up to 18-years old were evaluated in this cross-sectional study. All patients were examined for signs and symptoms of neuropathy and nerve conduction studies were performed. Blood level of glucose and lipid profiles were also tested. The relation between variables was compared by independent t-test and logistic regression test. Results: The mean age of diabetic children was 11.9 ± 3.3 years whereas mean diabetes duration was 3.8 ± 2.9 years. PNP was detected in 40 patients (27.4% that 62.5% of them have subclinical and 37.5% have clinical neuropathy. According to logistic regression analysis, duration of diabetes was the most important factor in prevalence of PNP (5.7 ± 3.5 and 3.1 ± 2.5 years in patients with and without neuropathy respectively, P < 0.001, 95% confidence interval [1.15-1.54]. Conclusion: As most of the patients had subclinical PN, neurological assessment is recommended to detect subclinical neuropathy in asymptomatic type 1 diabetic children and it seems that the best way to prevent this complication is still rigid blood glucose control and periodic evaluations.
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.
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
Full Text Available Ultrasound (US is one of the methods for imaging entrapment neuropathies, post-trau‑ matic changes to nerves, nerve tumors and postoperative complications to nerves. This type of examination is becoming more and more popular, not only for economic reasons, but also due to its value in making accurate diagnosis. It provides a very precise assess‑ ment of peripheral nerve trunk pathology – both in terms of morphology and localization. During examination there are several options available to the specialist: the making of a dynamic assessment, observation of pain radiation through the application of precise palpation and the comparison of resultant images with the contra lateral limb. Entrap‑ ment neuropathies of the upper limb are discussed in this study, with the omission of median nerve neuropathy at the level of the carpal canal, as extensive literature on this subject exists. The following pathologies are presented: pronator teres muscle syndrome, anterior interosseus nerve neuropathy, ulnar nerve groove syndrome and cubital tun‑ nel syndrome, Guyon’s canal syndrome, radial nerve neuropathy, posterior interosseous nerve neuropathy, Wartenberg’s disease, suprascapular nerve neuropathy and thoracic outlet syndrome. Peripheral nerve examination technique has been presented in previous articles presenting information about peripheral nerve anatomy [Journal of Ultrasonog‑ raphy 2012; 12 (49: 120–163 – Normal and sonographic anatomy of selected peripheral nerves. Part I: Sonohistology and general principles of examination, following the exam‑ ple of the median nerve; Part II: Peripheral nerves of the upper limb; Part III: Peripheral nerves of the lower limb]. In this article potential compression sites of particular nerves are discussed, taking into account pathomechanisms of damage, including predisposing anatomical variants (accessory muscles. The parameters of ultrasound assessment have been established – echogenicity and
Shoji, Satoshi; Suzuki, Misaki; Tomono, Yoshiro; Bockbrader, Howard N; Matsui, Shigeyuki
AIM Pregabalin, a chemical analogue of the mammalian neurotransmitter γ-aminobutyric acid, has been approved in many countries for partial-onset seizures, generalized anxiety disorder and various other pain disorders, including neuropathic pain associated with post-herpetic neuralgia and diabetic peripheral neuropathy and fibromyalgia. The aim of this study was to develop a population pharmacokinetic model and quantify the influence of covariates on the parameters. METHODS This pregabalin population pharmacokinetic analysis was conducted on data from 14 clinical trials involving healthy subjects, subjects with impaired renal function and patients with post-herpetic neuralgia or diabetic peripheral neuropathy (n = 616). The data analysis was performed using nonlinear mixed effects modelling methodology as implemented by NONMEM. RESULTS A one-compartment model with first-order absorption and elimination adequately described pregabalin pharmacokinetics. The model indicated that pregabalin apparent clearance (CL/F) was proportional to estimated creatinine clearance (CLcr). The pregabalin systemic exposure in patients with lower renal function who received pregabalin 150 mg twice daily was almost equal to that of patients with normal renal function administered pregabalin 300 mg twice daily. The systemic exposure stratified by lower or normal renal function was similar between patients with post-herpetic neuralgia and diabetic peripheral neuropathy. CONCLUSION The developed model identified CLcr and ideal body weight as clinically influential covariates on CL/F and volume of distribution, respectively. This study indicates that renal function accounts for variability in the apparent clearance of pregabalin which is consistent with what is known about the elimination of this drug. PMID:21306415
Jun 2, 2014 ... most common neuromuscular complications in HIV- infected (HIV+) patients. ... neuropathy, including older age, advanced HIV disease and history of ... nevirapine to prevent mother-to-child HIV transmission. Each woman ...
Marwan A. Ahmed
Full Text Available Peripheral neuropathy (PN is a primary complication of type 2 diabetes mellitus (T2DM and a direct manifestation of vitamin B12 deficiency. Examining the effects of metformin use on PN status became imperative following clinical studies that showed the vitamin B12-lowering effect of the medication. The complexity of the topic and the inconsistency of the results warrant consideration of topic-specific perspectives for better understanding of the available evidence and more appropriate design of future studies.
Slangen, Rachel; Faber, Catharina G; Schaper, Nicolaas C; Joosten, Elbert A; van Dongen, Robert T; Kessels, Alfons G; van Kleef, Maarten; Dirksen, Carmen D
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
Hussain, Gauhar; Rizvi, S Aijaz Abbas; Singhal, Sangeeta; Zubair, Mohammad; Ahmad, Jamal
To correlate serum levels of TGF-β1 with motor and sensory nerve conduction velocities in patients of type 2 diabetes mellitus The study was conducted in diagnosed type 2 diabetes mellitus patients which were divided in patients with clinically detectable peripheral neuropathy of shorter duration (n=37) and longer duration (n=27). They were compared with patients without clinical neuropathy (n=22). Clinical diagnosis was based on neuropathy symptom score (NSS) and Neuropathy disability score (NDS) for signs. Blood samples were collected for baseline investigations and estimation of serum TGF-β1. 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 In patients of type 2 diabetes mellitus with clinically detectable and serum TGF-β1 showed positive correlation with nerve conduction velocities High level of TGF-β1 in serum of T2DM patients with neuropathy show possible contribution in development of neuropathy. Due to its independent association this cytokine might be used as biomarker for diabetic peripheral neuropathy. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Andreja P. Picon
Full Text Available BACKGROUND: The progression of diabetes and the challenge of daily tasks may result in changes in biomechanical strategies. Descending stairs is a common task that patients have to deal with, however it still has not been properly studied in this population. OBJECTIVES: We describe and compare the net joint moments and kinematics of the lower limbs in diabetic individuals with and without peripheral neuropathy and healthy controls during stair descent. METHOD: Forty-two adults were assessed: control group (13, diabetic group (14, and neuropathic diabetic group (15. The flexor and extensor net moment peaks and joint angles of the hip, knee, and ankle were described and compared in terms of effect size and ANOVAs (p<0.05. RESULTS: Both diabetic groups presented greater dorsiflexion [large effect size] and a smaller hip extensor moment [large effect size] in the weight acceptance phase. In the propulsion phase, diabetics with and without neuropathy showed a greater hip flexor moment [large effect size] and smaller ankle extension [large effect size]. CONCLUSION: Diabetic patients, even without neuropathy, revealed poor eccentric control in the weight acceptance phase, and in the propulsion phase, they showed a different hip strategy, where they chose to take the leg off the ground using more flexion torque at the hip instead of using a proper ankle extension function.
Arnold, Lesley M; McCarberg, Bill H; Clair, Andrew G; Whalen, Ed; Thomas, Neal; Jorga, Anamaria; Pauer, Lynne; Vissing, Richard; Park, Peter W
The pregabalin dose-response for pain, Patient Global Impression of Change (PGIC), and sleep quality measures in painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN), and fibromyalgia (FM) is relevant for physicians treating these patients. This analysis aimed to demonstrate the dose-response of pregabalin for each indication and describe the onset (incidence), onset/continuation (prevalence), and resolution of adverse events (AEs) occurring during treatment. Data from 14 placebo-controlled, fixed-dose pregabalin trials in pDPN, PHN, and FM were pooled within each indication. Patients had mean baseline pain scores ≥6 on an 11-point numeric rating scale. A hyperbolic Emax dose-response model examined the dose-response of pregabalin for pain, PGIC, and sleep quality. Safety assessments included onset and prevalence of common AEs each week, and resolution in the first 2 months of treatment. In all indications, the likelihood of patients experiencing pain relief and improvements in PGIC and sleep quality increased in a dose-dependent manner with increasing doses. In all indications, new incidences of dizziness and somnolence were highest after 1 week of treatment, with few subsequent new reports at a given dose. Prevalence rates decreased steadily after 1 week of treatment. In FM, new onset weight gain emerged 6-8 weeks following treatment; prevalence rates generally increased then remained steady over time. With the exception of weight gain, many AEs resolved in month 1. The dose-response of pregabalin for pain, PGIC, and sleep quality was demonstrated, highlighting the benefit of achieving the maximum recommended dose of 300 mg/day for pDPN, 300-600 mg/day for PHN, and 300-450 mg/day for FM. Common AEs are generally seen within 1 week of starting treatment, with few subsequent new reports at a given dose. New onset weight gain occurs after 6 weeks of treatment, reinforcing the need for regular monitoring of weight.
Avas Chandra Ray
Full Text Available Neurofibromatosis 1 (NF1 is the most common neurocutaneous syndrome. It is estimated to occur in approximately 1 out of every 3300 infants. The manifestations of this condition are diverse and can arise from almost any system in the body. The neurofibroma is the hallmark lesion of NF1 that develops from peripheral nerves. Here, we are reporting an 18-year-old girl with NF1. Clinical diagnosis was made according to the diagnostic criteria established by the National Institutes of Health Consensus Development Conference in 1987. She presented with quadriparesis due to dumbbell-shaped spinal schwannoma in the cervical region. She had history of recurrent seizures in the past, with poor scholastic performance. There were clinical and electrophysiological features of peripheral neuropathy and clinical and echocardiographical features of pulmonary stenosis. These are uncommon features of NF 1. The presence of all these features in a single patient makes it a unique case.
López, Eva; Casasnovas, Carlos; Giménez, Javier; Santamaría, Raúl; Terrazas, Jesús M; Volpini, Víctor
Spastic paraplegia type 10 (SPG10) is a rare form of autosomal dominant hereditary spastic paraplegia (AD-HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy-chain involved in axonal transport. KIF5A mutations have been associated with a wide clinical spectrum, ranging from pure HSP to isolated peripheral nerve involvement or complicated HSP phenotypes. Most KIF5A mutations are clustered in the motor domain of the protein that is necessary for microtubule interaction. Here we describe two Spanish families with an adult onset complicated AD-HSP in which neurological studies revealed a mild sensory neuropathy. Intention tremor was also present in both families. Molecular genetic analysis identified two novel mutations c.773 C>T and c.833 C>T in the KIF5A gene resulting in the P258L and P278L substitutions respectively. Both were located in the highly conserved kinesin motor domain of the protein which has previously been identified as a hot spot for KIF5A mutations. This study adds to the evidence associating the known occurrence of mild peripheral neuropathy in the adult onset SPG10 type of AD-HSP. Copyright © 2015 Elsevier B.V. All rights reserved.
Baszyńska-Wilk, Marta; Wysocka-Mincewicz, Marta; Świercz, Anna; Świderska, Jolanta; Marszał, Magdalena; Szalecki, Mieczysław
Neurological complications of diabetic ketoacidosis are considered to be very serious clinical problem. The most common complication is cerebral edema. However this group includes also less common syndromes such as ischemic or hemorrhagic stroke, cerebral venous and sinus thrombosis or very rare peripheral neuropathy. We present a case of 9-year old girl with new onset type 1 diabetes, diabetic ketoacidosis, cerebral edema, multifocal vasogenic brain lesions and lower limbs peripheral paresis. The patient developed polydipsia and polyuria one week before admission to the hospital. In laboratory tests initial blood glucose level 1136 mg/dl and acidosis (pH 7.1; BE-25.9) were noted. She was admitted to the hospital in a critical condition and required treatment in intensive care unit. Computed tomography scan showed brain edema and hipodense lesion in the left temporal region. Brain MRI revealed more advanced multifocal brain lesions Nerve conduction studies demonstrated damage of the motor neuron in both lower extremities with dysfunction in both peroneal nerves and the right tibial nerve. As a result of diabetological, neurological treatment and physiotherapy patient's health state gradually improved. Acute neuropathy after ketoacidosis is rare complication and its pathomechanism is not clear. Patients with DKA require careful monitoring of neurological functions even after normalization of glycemic parameters.
Vahdat, Linda T; Garcia, Agustin A; Vogel, Charles; Pellegrino, Christine; Lindquist, Deborah L; Iannotti, Nicholas; Gopalakrishna, Prashanth; Sparano, Joseph A
Peripheral neuropathy is a common toxicity associated with tubulin-targeted chemotherapeutic agents. This Phase II study compares the incidence and severity of neuropathy associated with eribulin mesylate or ixabepilone in metastatic breast cancer (MBC). The primary objective was to assess the incidence of neuropathy; the study was designed to detect a difference in neuropathy rate of 35 % for eribulin versus 63 % for ixabepilone (odds ratio 0.316, 80 % power, 0.05 two-sided significance level). Eligibility criteria included: MBC; prior taxane therapy; at least one chemotherapy for advanced disease; no or minimal pre-existing neuropathy (Grade 0 or 1). The intent-to-treat population comprised 104 patients randomized (1:1) to eribulin mesylate (1.4 mg/m(2), 2-5 min intravenous on days 1 and 8) or ixabepilone (40 mg/m(2), 3 h intravenous on day 1) on a 21-day cycle. 101 patients in the safety population received a median of 5.0 eribulin and 3.5 ixabepilone cycles. Incidence of neuropathy (any grade) was 33.3 and 48.0 %, and peripheral neuropathy was 31.4 and 44.0 % for eribulin and ixabepilone, respectively. After controlling for pre-existing neuropathy and number of prior chemotherapies, these differences were not significant. Compared with ixabepilone, fewer patients receiving eribulin discontinued treatment due to neuropathy (3.9 vs. 18.0 %) or adverse events (AEs) in general (11.8 vs. 32.0 %). Time to onset of neuropathy was 35.9 weeks for eribulin and 11.6 weeks for ixabepilone, and time to resolution was 48 versus 10 weeks, respectively; other AEs were comparable. Objective responses were 15.4 versus 5.8 % and clinical benefit rates were 26.9 versus 19.2 %. In conclusion, after controlling for pre-existing neuropathy and number of prior chemotherapies, the differences in the incidence of neuropathy with eribulin and ixabepilone were not statistically significant. Onset of neuropathy tended to occur later with eribulin and resolve later.
Sinacore, David R.; Cade, W. Todd; Mueller, Michael J.
Background Increased lipid accumulation in skeletal muscle has been linked to insulin resistance, impaired muscle performance, and impaired physical function. It is unclear whether physical activity is associated with lipid content in skeletal muscle, muscle performance, or overall physical function. Objective The purpose of this study was to characterize physical activity levels (average daily step count) in a sample of people with diabetes and peripheral neuropathy and to determine the relationship among step count, intermuscular adipose tissue volume (IMAT), muscle performance (peak torque, power), and physical function. Design A cross-sectional design was used in this study. Methods Twenty-two people with diabetes and peripheral neuropathy (15 men and 7 women, mean age=64.5 years [SD=12.7], and mean body mass index=33.2 kg/m2 [SD=6.4]) participated. Average daily step count, glycosylated hemoglobin, modified 9-item Physical Performance Test scores, Six-Minute Walk Test distance, calf intermuscular adipose tissue volume (via magnetic resonance imaging), and isokinetic dynamometry of the ankle muscles were recorded. Results Average daily step count was 7,754 (SD=4,678; range=3,088–20,079). Five participants had an average daily step count greater than 10,000. Average IMAT volume was 84 cm3 (SD=88). Greater average daily step count was associated with younger age (r=−.39, P<.05) and with lower IMAT volume in the calf (r=−.44, P<.05). Lower IMAT volume was associated with greater muscle performance (r=−.45) and physical function (r=−.43 to −.48). Limitations The sample in this study may be biased toward people with high levels of activity because participants were recruited for an exercise study. The results should not be generalized to people taking fewer than 3,000 steps/day or to those with a current foot ulcer, peripheral arterial disease, or severe foot deformity or amputation or who weigh more than 136 kg (300 lb). Conclusions Average daily step
Full Text Available We have tested serum samples from 24 patients with multifocal motor neuropathy (MMN for reactivity to ganglioside GM1 and to Gal(β1–3GalNAc-bearing glycoproteins isolated from human peripheral nerve and from Campylobacter jejuni (Cj serotype O:19. IgM anti-GM1 antibodies were detected by ELISA in 11 patients (45.8% with MMN and in only one subject (4% from the control group. Western blots showed positive reactivity of sera from 6 patients (25% with MMN to several Gal(β1–3GalNAc-bearing glycoproteins from human peripheral nerve and from Cj O:19 isolates. Sera from three patients (12.5% with MMN showed positively reactive bands with similar electrophoretic mobility in all isolates (60–62 kDa, 48–51 kDa, 42 kDa, and 38 kDa. All six patients showed positive reactivity to 48–52 kDa protein isolated from human peripheral nerve. Increased titer of IgG antibodies to 60–62 kDa protein isolated from Cj O:19 associated with Guillain-Barré syndrome was detected in three patients, and their serum showed also IgG positive reactivity to peripheral nerve antigen with the same electrophoretic mobility. One of these patients had a previous history of Cj infection which suggests the possibility that Cj may be also involved in the pathogenesis of MMN.
van Schaik, I. N.; Bouche, P.; Illa, I.; Léger, J.-M.; van den Bergh, P.; Cornblath, D. R.; Evers, E. M. A.; Hadden, R. D. M.; Hughes, R. A. C.; Koski, C. L.; Nobile-Orazio, E.; Pollard, J.; Sommer, C.; van Doorn, P. A.
Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus
Gill, H K; Yadav, S B; Ramesh, V; Bhatia, E
Diabetic peripheral neuropathy (DPN) predisposes to foot ulceration and gangrene. It has been reported that DPN is lower in Indians relative to Caucasians. Studies among recent onset patients with type 2 diabetes mellitus (T2DM) are very few. We studied the prevalence and risk factors of DPN in patients with newly diagnosed T2DM. We prospectively studied 195 consecutive patients over age 30 with a duration of diabetes ≤6 months. All underwent a clinical and biochemical evaluation and were screened for DPN using Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) as well as the vibration perception threshold using a biothesiometer. We compared the prevalence of peripheral neuropathy (PN) in 75 age- and sex-matched healthy controls. The cases had a mean age of 47.6 ± 10.2 years (59% males) and duration of symptoms of 5.9 ± 8.2 months prior to presentation. The overall prevalence of DPN was 29.2% [95% CI 22.8-35.7]. PN among matched control was 10.7% (95% CI 3.5-17.8). The prevalence of DPN showed an increasing trend with age (trend chi-square 11.8, P = 0.001). Abnormal vibration perception threshold was present in 43.3% (95% CI 36.3-50.3) of cases and had a significant correlation with NDS (P = 0.000). Abnormal monofilament testing was present in 6.1% of cases (95% CI 2.7- 9.5). A logistic regression analysis showed that DPN was independently associated with age (P = 0.002) and duration of diabetes prior to presentation (P = 0.02) but not with body mass index, plasma glucose, or HbA1c. Our study showed high prevalence of PN in recently diagnosed patients with T2DM, which was independently associated with age and duration of symptoms of diabetes prior to the diagnosis. Screening for DPN at diagnosis of diabetes is warranted, especially among older subjects.
Full Text Available Background and Objective: Diabetes is associated with many complications that one of these complications is neuropathy. This disease is more common in women. In cases of self-care deficit and not meeting its related needs, the disease can lead to complications and even death. This study was done to determine the self care ability of diabetes women with peripheral neuropathy and its related need based on Orem self care model. Materials and Method: This cross - sectional study was conducted on women with diabetic peripheral neuropathy who referred to diabetes clinic in one of the hospitals in Gonabad in 2014. 120 patients were selected by convenience sampling. Patients’ neuropathy was determined by Michigan Neuropathy Screening Instrument and Toronto Clinical Neuropathy Score. Then, data were gathered through using self care needs assessment questionnaire and self care ability questionnaire based on Orem self care model. Data analysis was done through using descriptive statistical test and chi-square test with in SPSS 17. Results: The self care ability of 71.7 percent of patients was weak (33.72 ± 8.48 and according to needs assessment and in domains of knowledge, attitude and performance, 10.8, 0.8 and 52.5 percent of subjects were weak respectively. Conclusion: According to the findings, the self care ability of diabetic women with peripheral neuropathy was weak. The domain of performance was weaker than attitude and knowledge domains concerning the self care ability. Therefore, it is recommended to design and implement of necessary measures for improving the patients’ self care ability based on their needs.
Carod-Artal, F J; del Negro, M C; Vargas, A P; Rizzo, I
Type I human T-cell lymphotropic virus (HTLV-I) is a retrovirus with affinity for CD4 cells. This infection may give rise to a broad spectrum of disorders including T-cell leucemia/lymphoma, the myelopathy/tropical spastic paraparesis complex (M/TSP), and to a lesser extent, uveitis, arthritis, polymyositis and peripheral neuropathy. M/TSP is a progressive, chronic myelopathy characterized by spasticity, hypereflexia, muscle weakness and sphincter disorders. Much less frequently it may precede, or give rise to, a cerebellar syndrome with ataxia and intention tremor. We describe the case of a 13 year old adolescent girl who presented with a neurological syndrome which had started with tremor of the head and limbs, ataxia, dysmetria, frequent falls and sphincter disorders. During the two and a half years that she had had this illness she had developed spastic paraparesis of the legs and had repeated urinary infections. Serology of blood and CSF was positive for HTLV-I using the ELISA technique and confirmed by Western-blot. EMG showed predominantly axonal sensomotor neuropathy. A neurogenic bladder was detected on functional urodynamic studies. On MR there was moderate atrophy of the thoracic spinal cord and slight alterations of the subcortical white matter. The presence of a cerebellar syndrome or neuropathy of uncertain origin, in endemic areas, should lead to the inclusion of HTLV-I infection in the differential diagnosis, even in the absence of pyramidal symptoms or defined M/TSP. Maternal seropositivity supports the hypothesis of mother-daughter transmission during lactation.
Full Text Available Abstract Introduction Ethylene glycol poisoning may pose diagnostic difficulties if the history of ingestion is not volunteered, or if the presentation is delayed. This is because the biochemical features of high anion-gap metabolic acidosis and an osmolar gap resolve within 24 to 72 hours as the ethylene glycol is metabolized to toxic metabolites. This case illustrates the less well-known clinical features of delayed ethylene glycol poisoning, including multiple cranial and peripheral neuropathies, and the clinical findings which may point towards this diagnosis in the absence of a history of ingestion. Case presentation A 53-year-old Afro-Caribbean man presented with vomiting, abdominal pain and oliguria, and was found to have acute renal failure requiring emergency hemofiltration, and raised inflammatory markers. Computed tomography imaging of the abdomen revealed the appearance of bilateral pyelonephritis, however he failed to improve with broad-spectrum antibiotics, and subsequently developed multiple cranial neuropathies and increasing obtundation, necessitating intubation and ventilation. Computed tomography of the brain showed no focal lesions, and a lumbar puncture revealed a raised cerebrospinal fluid opening pressure and cyto-albuminological dissociation. Nerve conduction studies revealed a sensorimotor radiculoneuropathy mimicking a Guillain-Barre type lesion with an atypical distribution. It was only about two weeks after presentation that the history of ethylene glycol ingestion one week before presentation was confirmed. He had a slow recovery on the intensive care unit, requiring renal replacement therapy for eight weeks, and complicated by acute respiratory distress syndrome, neuropathic pain and a slow neurological recovery requiring prolonged rehabilitation. Conclusions Although neuropathy as a result of ethylene glycol poisoning has been described in a few case reports, all of these were in the context of a known history of
Wormser, Gary P; Strle, Franc; Shapiro, Eugene D; Dattwyler, Raymond J; Auwaerter, Paul G
In older studies, a chronic distal symmetric sensory neuropathy was reported as a relatively common manifestation of late Lyme disease in the United States. However, the original papers describing this entity had notable inconsistencies and certain inexplicable findings, such as reports that this condition developed in patients despite prior antibiotic treatment known to be highly effective for other manifestations of Lyme disease. More recent literature suggests that this entity is seen rarely, if at all. A chronic distal symmetric sensory neuropathy as a manifestation of late Lyme disease in North America should be regarded as controversial and in need of rigorous validation studies before acceptance as a documented clinical entity. Copyright © 2016 Elsevier Inc. All rights reserved.
Jennifer J. Brown
Full Text Available Objective. Examine the effectiveness of the 128 Hz tuning fork, two monofilaments, and Norfolk Quality of Life Diabetic Neuropathy (QOL-DN questionnaire as tools for the early detection of diabetic peripheral neuropathy (DPN in overweight, obese, and inactive (OOI adults or those who have prediabetes (PD or type 2 diabetes (T2D. Research Design and Methods. Thirty-four adults (mean age 58.4 years ± 12.1 were divided by glycemia (10 OOI normoglycemic, 13 PD, and 11 T2D. Sural nerves were tested bilaterally with the NC-stat DPNCheck to determine sural nerve amplitude potential (SNAP and sural nerve conduction velocity (SNCV. All other testing results were compared to SNAP and SNCV. Results. Total 1 g monofilament scores significantly correlated with SNAP values and yielded the highest sensitivity and specificity combinations of tested measures. Total QOL-DN scores negatively correlated with SNAP values, as did QOL-DN symptoms. QOL-DN activities of daily living correlated with the right SNAP, and the QOL-DN small fiber subscore correlated with SNCV. Conclusions. The 1 g monofilament and total QOL-DN are effective, low-cost tools for the early detection of DPN in OOI, PD, and T2D adults. The 128 Hz tuning fork and 10 g monofilament may assist DPN screening as a tandem, but not primary, early DPN detection screening tools.
Full Text Available Aim of this study was to evaluate the prevalence of plantar fascia (PF enthesopathy in Type 2 diabetes mellitus (T2DM patients without distal peripheral neuropathy (DPN.We recruited 50 T2DM patients without DPN and 50 healthy controls. DPN was excluded using the Michigan Neuropathy Screening Instrument (MNSI. All patients underwent a bilateral sonographicevaluation of the enthesealportion of the PF.PF thickness was significantly higher in T2DM patients (p<0.0001. T2DM patients presented a higher prevalence of entheseal thickening (p = 0.002, enthesophyte (p = 0.02 and cortical irregularity (p = 0.02. The overall sum of abnormalities was higher in T2DM patients (p<0.0001, as was the percentage of bilateral involvement (p = 0.005. In a logistic regression analysis, retinopathy predicted entheseal thickening (OR 3.5, p = 0.05 and enthesophytes (OR 5.13, p = 0.001; reduced eGFR predicted enthesophytes (OR 2.93, p = 0.04; body mass index (BMI predicted cortical irregularity (OR 0.87, p = 0.05; mean glucose predicted enthesophyte (OR 1.01, p = 0.03; LDL cholesterol predicted cortical irregularity (OR 0.98, p = 0.02.Our data suggest that T2DM is associated with PF enthesopathyindependently of DPN.
Joo Young Jung
Full Text Available Bortezomib-induced peripheral neuropathy (BiPN in multiple myeloma (MM patients is a common and serious side effect. Currently, it has been reported that subcutaneous (SC administration of bortezomib decreases the incidence of BiPN as compared to standard intravenous (IV bolus injection without any differences in efficacy. However, there are reports of severe injection site reaction following SC administration of bortezomib. The aim of this study was to evaluate the response rate and incidence of BiPN following one-hour IV infusion of bortezomib. The data was retrospectively collected from MM patients who had been treated with IV administration of bortezomib for one hour. Twenty-three patients were evaluated (median age 72 years, 13 males. The median number of treatment cycles was 5 (range 2–10. The cumulative bortezomib dose was 26.0 mg/m2 (14.3–66.3 and percent of actual per expected cumulative dose was 90% (50–100. The overall response (complete response plus partial response rate was 65%. The incidence of BiPN was 57% (n = 13 and incidence of severe neuropathy was 4% (n = 1. One-hour IV infusion of bortezomib was an effective regimen for MM with reduced incidence of severe BiPN. This route of administration of bortezomib could be an alternative mode of delivery for patients with severe injection site reactions following SC administration.
Mchugh, John C
INTRODUCTION: Despite theoretical advantages, the practical impact of mathematical correction of normative electrodiagnostic data is poorly quantified. METHODS: One hundred five healthy volunteers had clinical and neurophysiological assessment. The effects of age, height, gender, weight, and body mass index were explored using stepwise regression modeling. Reference values were derived from raw and adjusted data, which were transformed to allow appropriate use of parametric statistics. The diagnostic accuracy of derived limits was tested in patients at risk of distal symmetric peripheral neuropathy (DSPN) from chemotherapy. RESULTS: The variability of our normative data was reduced by up to 69% through the use of regression modeling, but the overall benefits of mathematical correction were marginal. The most accurate reference limits were established using the 2.5th and 97.5th percentiles of the raw data. CONCLUSIONS: Stepwise statistical regression and mathematical transformation improve the distribution of normative data, but their practical impact for diagnosis of distal symmetrical polyneuropathy is small.
Barak, Y; Arnon, S; Wolach, B; Raz, Y; Ashkenasi, A; Glick, B; Shapira, Y
A 4-year-old boy presented with developmental delay, aggressive behavior, and incoordination. His EEG showed a diffuse encephalopathy. At age 10 he developed convulsions and severe migraine-like headaches. Muscle wasting, arreflexia, and lactic acidemia following exercise were noted. Electromyography was myopathic and nerve conduction studies revealed a peripheral neuropathy. Muscle biopsy demonstrated variation in fiber size and an excess of lipid droplets. He than had several stroke-like episodes and periods of unconsciousness, associated with severe metabolic acidosis. Muscle cytochrome C oxidase was abnormally low. This boy displayed the classical clinical and biochemical features of MELAS syndrome, namely Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes. Treatment included carnitine, vitamin C, vitamin K, riboflavin, coenzyme Q10, and corticosteroids. He died at the age of 14 years following an episode of seizures, coma, and gastrointestinal hemorrhage. This is the first reported case of MELAS syndrome in Israel.
European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of multifocal motor neuropathy. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision
van Schaik, Ivo N.; Leger, Jean-Marc; Nobile-Orazio, Eduardo; Cornblath, David R.; Hadden, Robert D. M.; Koski, Carol L.; Pollard, John D.; Sommer, Claudia; Illa, Isabel; van den Bergh, Peter; van Dorrn, Pieter A.
A European Federation of Neurological Societies/Peripheral Nerve Society consensus guideline on the definition, investigation, and treatment of multifocal motor neuropathy (MMN) was published in 2006. The aim is to revise this guideline. Disease experts considered references retrieved from MEDLINE
Callinan, R B; Jiang, L; Smith, P T; Soowannayan, C
Lesions are described in farmed Penaeus monodon affected with a previously unreported, fatal disease, 'peripheral neuropathy and retinopathy' (PNR). Outbreaks, associated with minor to heavy mortalities, occurred in 22 of 25 ponds on a farm in eastern Australia during the mid to late 1998/99 growout period. Moribund prawns, 5 to 26 g mean body weight, gathered at pond edges and were typically reddish in colour, lethargic, with mild to moderate epibiotic fouling and 1 or more partially amputated appendages. Histologically, there was mild to severe, focal to diffuse degeneration and necrosis of axons and their sheaths, together with associated glial cell apoptosis, in peripheral nerve fibres. Of the 3 appendage types examined systematically, these pathognomonic lesions were most common and severe in proximal antennal nerves and less common and severe in distal antennal nerves, antennular nerves and pereiopod nerves. Mild to severe, acute to chronic retinitis, associated with degeneration and necrosis of retinular cells and their axons, was also present in most clinically affected prawns. Transmission electron microscopy revealed moderate to large numbers of intracytoplasmic rod-shaped, helical nucleocapsids and enveloped virions, morphologically consistent with a yellow head-like virus, in putative glial cells in the antennal nerve, in the fasciculated zone of the eye and in putative sensory nerve cells of antennules. Immunohistochemical examination revealed lesions, but not histologically normal tissues, in peripheral nerves, eyes, lymphoid organ and vas deferens that consistently stained positively for a yellow head-related virus. The findings strongly suggest that a yellow head-related virus such as the Australian gill-associated virus (GAV) is causally associated with PNR. It is likely that PNR was not recognised during earlier investigations of mid-crop mortalities of farmed P. monodon in eastern Australia because appropriate peripheral nerves and eyes were not
Abeer A. Yamany
Full Text Available Diabetic neuropathy is the most common complication and greatest source of morbidity and mortality in diabetic patients. Thirty male and female patients with painful diabetic neuropathy and abnormal results from nerve conduction studies participated in this study. Their ages ranged from 45 to 60 years with a mean of 52.1 ± SD 4.7 years. Patients were randomly assigned into two equal groups of 15, an active laser group (laser group and a placebo laser group (control group. The laser group received scanning helium neon (He–Ne infrared laser with wavelength 850 nm and density of 5.7 J/cm2, applied to the lumbosacral area and the plantar surface of the foot for 15 min each site/session three times per week for four weeks (i.e. 12 sessions. Pain intensity via visual analogue scale, bilateral peroneal motor nerves, sural sensory nerves conduction velocity and amplitude and foot skin microcirculation, were measured pre- and post-treatment for both groups. Pain was significantly decreased (p ⩽ 0.05 and electrophysiological parameters and foot skin microcirculation were significantly improved (p ⩽ 0.05 in the laser group, while no significant change was obtained in the control group. Low level laser therapy within the applied parameters and technique could be an effective therapeutic modality in reducing pain and improving neurovascular function in patients with diabetic polyneuropathy.
Pachman, Deirdre R; Qin, Rui; Seisler, Drew; Smith, Ellen M Lavoie; Kaggal, Suneetha; Novotny, Paul; Ruddy, Kathryn J; Lafky, Jacqueline M; Ta, Lauren E; Beutler, Andreas S; Wagner-Johnston, Nina D; Staff, Nathan P; Grothey, Axel; Dougherty, Patrick M; Cavaletti, Guido; Loprinzi, Charles L
Oxaliplatin and paclitaxel are commonly used chemotherapies associated with acute and chronic neuropathies. There is a need to better understand the similarities and differences of these clinical syndromes. Neuropathy data were pooled from patients receiving adjuvant oxaliplatin and weekly paclitaxel or every 3 weeks of paclitaxel. Patients completed daily questionnaires after each chemotherapy dose and the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy before each chemotherapy cycle and for 12 months post-treatment. Acute neuropathy symptoms from both drugs peaked around day 3. Acute symptoms experienced in cycle 1 predicted occurrence in subsequent cycles. Paclitaxel-induced acute symptoms were similar in intensity in each cycle and largely resolved between cycles. Oxaliplatin-induced acute symptoms were about half as severe in the first cycle as in later cycles and did not resolve completely between cycles. Both drugs caused a predominantly sensory chronic neuropathy (with numbness and tingling being more common than pain). Oxaliplatin-induced neuropathy worsened after the completion of treatment and began to improve 3 months post-treatment. In contrast, paclitaxel-induced neuropathy began improving immediately after chemotherapy cessation. During treatment, the incidence of paclitaxel sensory symptoms was similar in the hands and feet; with oxaliplatin, the hands were affected more than the feet. Both paclitaxel- and oxaliplatin-induced acute neurotoxicity appeared to predict the severity of chronic neuropathy, more prominently with oxaliplatin. Knowledge of the similarities and differences between neuropathy syndromes may provide insight into their underlying pathophysiology and inform future research to identify preventative treatment approaches.
Sangild, Per T; Shen, René Liang; Pontoppidan, Peter Erik Lotko
mangement and treatments. The results obtained from specific animal models can be difficult to translate to the diverse range of CIM manifestations in patients that vary according to the antineoplastic drugs, dose, underlying (cancer) disease and patient characteristics (e.g. age, genetics, body......Chemotherapy for cancer patients induces damaging tissue reactions along the epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced mucositis (CIM) is a serious side effect of cytotoxic drugs and several animal models of CIM have been developed to help understand the progression...... of CIM, and how to prevent it. Animal models allow highly controlled experimental conditions, detailed organ (e.g. GIT) insights, standardized, clinically-relevant treatment regimens and discovery of new biomarkers. Still, surprisingly few results from animal models have been translated into clinical CIM...
Full Text Available Many cases of atopic myelitis have been reported in Japan; however very few were described in western countries. An 82-year-old woman with a past medical history of atopic dermatitis and asthma presented with progressive paresthesia (tingling of both hands and tetraparesis. Before the onset of neurological symptoms, she complained of ichthyosis of both legs for 5 weeks. Magnetic resonance imaging demonstrated multisegmental degenerative arthritis, degenerative disc disease, and abnormal spinal cord signal intensity over several cervical segments, suggesting the diagnosis of myelitis. Total serum IgE level was elevated. Nerve conduction studies revealed asymmetric axonal sensorimotor neuropathy. The cerebrospinal fluid specimen showed lymphocytic pleocytosis and elevated protein level. Based on clinical, imaging, and laboratory findings, atopic myelitis was diagnosed. The diagnosis of atopic myelitis should be considered in myelopathy patients with history of atopy and elevated serum IgE levels.
Full Text Available Background. The burden of diabetes mellitus (DM is on the rise especially in developing countries like India. Due to its chronic nature DM tends to cause many debilitating complications and diabetic peripheral neuropathy (DPN is one of them. The aim of this study is to determine the prevalence of DPN among patients attending a tertiary care hospital and to identify the determinants associated with it. Design and methods. A cross sectional study was conducted in Government Wenlock Hospital, Mangalore (India, during January-February 2014. A total of 208 patients with >5 year duration of DM were asked to respond to the patient history version of Michigan Neuropathy Screening Instrument (MNSI and examinations were conducted after obtaining consent from them. The statistical analysis was done in terms of descriptive statistics and association between variables was tested using logistic regression test.Results. The prevalence of DPN using the MNSI history version and MNSI examination were found to be 18.3% and 32.2% respectively. The major determinants associated with DPN were found to be male gender (OR: 2.7, CI: 1.4-5.1, P=0.001, smoking (OR: 5.8, CI: 1.9-17.3, P=0.001 and age >40 years (OR: 2.7, CI: 1.2-5.8, P=0.011. Conclusions. The burden of undetected DPN was found to be higher among diabetics, with an especially higher prevalence among males, smokers and those with long standing diabetes mellitus. Interventions in the form of early detection through routine screening, smoking cessation and regular follow up examinations would go a long way in reducing the burden of disability among diabetics and improve their quality of life significantly.
Monti Bragadin, M; Francini, L; Bellone, E; Grandis, M; Reni, L; Canneva, S; Gemelli, C; Ursino, G; Maggi, G; Mori, L; Schenone, A
The combination of distal muscle weakness, sensory defects and feet deformities leads to disequilibrium in patients affected by Charcot-Marie-Tooth (CMT) neuropathy. Studies relating the outcome of balance scales and clinical severity of CMT are lacking. To evaluate the accuracy of the Tinetti Balance scale (TBS) and Berg Balance scale (BBS) in identifying balance disorders and quantifying disease severity in CMT patients. Observational study. University of Genoa-IRCCS AOU San Martino IST-Department of Neurology, Italy. Nineteen individuals with a diagnosis of CMT (12 females, 7 males, age 41.26±12.42). All subjects underwent an evaluation with both TBS and BBS. Disability was quantified with CMT neuropathy score (CMTNS). Moreover, a complete neurophysiological study was performed. Distal lower limbs strength was evaluated with MRC scale. Pearson rank order correlation was used to determine the correlation between the scores on the two tests and to identify an eventual correlation between TBS or BBS and the CMTNS. Both scales showed a highly significant negative correlation with the CMTNS (r=-0.78, P<0.0005 and r=-0.77, P<0.001, respectively) and distal weakness on the anterior tibial muscles (AT) (TBS: AT left: r=0.65, P<0.005 and AT right: 0.59, P<0.01; BBS: AT left r=+0.71, P<0.001 and AT right r=+0.66, P<0.005). We found also a highly significant, positive correlation between the two different balance scales (r=+0.9, P<0.0001). TBS and BBS strongly correlate with disease disability and distal muscular weakness. Both TBS and BBS may play a relevant role in the assessment of disability in patients affected by CMT. Further studies are needed to validate our results in a larger population.
Nerve excitability (NE) testing is a sensitive method to test for peripheral neurotoxicity in humans,and may be more sensitive than compound nerve action potential (CNAP) or nerve conduction velocity (NCV).We used acrylamide to compare the NE and CNAP/NCV methods. Behavioral test...
Breitschwerdt, Edward B; Mascarelli, Patricia E; Schweickert, Lori A; Maggi, Ricardo G; Hegarty, Barbara C; Bradley, Julie M; Woods, Christopher W
A young woman experiencing depression, anxiety, mood swings, severe headaches, muscle spasms, interphalangeal joint stiffness, decreased peripheral vision, diminished tactile sensation, and hallucinations was persistently Bartonella koehlerae seroreactive and bacteremic. Following antibiotic treatment, B. koehlerae antibodies and DNA were not detected and all symptoms resolved.
Full Text Available 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.
Wheeler, Heather E; Gamazon, Eric R; Wing, Claudia; Njiaju, Uchenna O; Njoku, Chidiamara; Baldwin, Robert Michael; Owzar, Kouros; Jiang, Chen; Watson, Dorothy; Shterev, Ivo; Kubo, Michiaki; Zembutsu, Hitoshi; Winer, Eric P; Hudis, Clifford A; Shulman, Lawrence N; Nakamura, Yusuke; Ratain, Mark J; Kroetz, Deanna L; Cox, Nancy J; Dolan, Mary Eileen
We sought to show the relevance of a lymphoblastoid cell line (LCL) model in the discovery of clinically relevant genetic variants affecting chemotherapeutic response by comparing LCL genome-wide association study (GWAS) results to clinical GWAS results. A GWAS of paclitaxel-induced cytotoxicity was conducted in 247 LCLs from the HapMap Project and compared with a GWAS of sensory peripheral neuropathy in patients with breast cancer (n = 855) treated with paclitaxel in the Cancer and Leukemia Group B (CALGB) 40101 trial. Significant enrichment was assessed by permutation resampling analysis. We observed an enrichment of LCL cytotoxicity-associated single-nucleotide polymorphisms (SNP) in the sensory peripheral neuropathy-associated SNPs from the clinical trial with concordant allelic directions of effect (empirical P = 0.007). Of the 24 SNPs that overlap between the clinical trial (P architecture of related traits in patients. ©2012 AACR.
Marcellin, Patrick; Wursthorn, Karsten; Wedemeyer, Heiner; Chuang, Wan-Long; Lau, George; Avila, Claudio; Peng, Cheng-Yuan; Gane, Edward; Lim, Seng Gee; Fainboim, Hugo; Foster, Graham R; Safadi, Rifaat; Rizzetto, Mario; Manns, Michael; Bao, Weibin; Trylesinski, Aldo; Naoumov, Nikolai
This study investigated the antiviral efficacy and safety of telbivudine in combination with pegylated interferon (PegIFN) alpha-2a in chronic hepatitis B (CHB) patients. This was a randomized, open-label, multicentre study, in treatment-naïve patients with HBeAg-positive CHB, comparing the efficacy and safety of telbivudine in combination with PegIFN alpha-2a with telbivudine monotherapy and PegIFN alpha-2a monotherapy. The study was terminated early due to increased rates of peripheral neuropathy in the combination-therapy group. Of the 159 patients randomized (from 300 planned) 50 were assigned to combination therapy, 55 to telbivudine, 54 to PegIFN, and 110 (18, 49, and 43, respectively) reached week 24. Peripheral neuropathy occurred in 7/50, 1/54, and 0/54 patients in the three groups of safety populations, respectively. No relationship between the occurrence of peripheral neuropathy and other variables (e.g., pharmacokinetic data, treatment efficacy, ALT levels, creatine kinase elevations) were observed. At week 24, undetectable HBV DNA (<300 copies/ml) was achieved by 71% (12/17), 35% (17/48), and 7% (3/42) of patients, with available data receiving combination therapy, telbivudine monotherapy and PegIFN monotherapy, respectively (p = 0.022 for combination therapy vs. telbivudine; p<0.0001 for combination therapy vs. PegIFN). Combination therapy carried an increased risk of peripheral neuropathy. Despite the rapid and profound reductions in HBV DNA levels, combination therapy with telbivudine and PegIFN should not be used. Copyright © 2014. Published by Elsevier B.V.
Chin, Yen-Fan; Huang, Tzu-Ting; Hsu, Brend Ray-Sea
To identify the effects of health belief model factors on daily foot-exam practice among diabetes mellitus patients with peripheral neuropathy. Daily foot exams are one of the most important self-care behaviours that prevent the occurrence of diabetic foot ulcers and subsequent amputation. Although daily foot exams were under-practiced in patients with peripheral neuropathy, few studies have explored modifiable social-psychological factors related to daily foot exams. A cross-sectional survey was used to collect the data. A total of 277 patients with diabetes and peripheral neuropathy were recruited from two hospitals in northern Taiwan. The Family APGAR and Diabetic Foot Ulcer Health Belief Scale (DFUHBS) were used to measure family support and health belief factors respectively. Data on foot-exam practice, perceived self-efficacy and action cues were collected through the use of structured questionnaires. The data were analysed using logistic regression. The regression model revealed that select action cues (recommendations from family, friends, or health professionals), perceived self-efficacy and perceived barriers interactively influenced the participants' daily foot-exam practice. Factors related to daily foot-exam practice were identified. Specifically, action cues played a significant role in motivating daily foot-exam practice in this group. This study recognises modifiable factors that influence the daily foot-exam practice of patients with diabetes and peripheral neuropathy. Using the findings of this study, health professionals can design interventions that aim to modify the above factors as a means to promote daily foot-exam practice. © 2012 Blackwell Publishing Ltd.
Current Status of Diabetic Peripheral Neuropathy in Korea: Report of a Hospital-Based Study of Type 2 Diabetic Patients in Korea by the Diabetic Neuropathy Study Group of the Korean Diabetes Association
Jong Chul Won
Full Text Available Diabetic peripheral neuropathy (DPN is the most common complication associated with diabetes. DPN can present as a loss of sensation, may lead to neuropathic ulcers, and is a leading cause of amputation. Reported estimates of the prevalence of DPN vary due to differences in study populations and diagnostic criteria. Furthermore, the epidemiology and clinical characteristics of DPN in Korean patients with type 2 diabetes mellitus (T2DM are not as well understood as those of other complications of diabetes such as retinal and renal disease. Recently, the Diabetic Neuropathy Study Group of the Korean Diabetes Association (KDA conducted a study investigating the impact of DPN on disease burden and quality of life in patients with T2DM and has published some data that are representative of the nation. This review investigated the prevalence and associated clinical implications of DPN in Korean patients with diabetes based on the KDA study.
Qiao, Xiaona; Zhang, Shuo; Zhao, Weiwei; Ye, Hongying; Yang, Yehong; Zhang, Zhaoyun; Miao, Qing; Hu, Renming; Li, Yiming; Lu, Bin
Neurofilament (NF), one of the major axonal cytoskeletal proteins, plays a critical role in degenerative diseases in both the central and the peripheral nervous systems. The aim of this study is to explore the relationship between serum phosphorylated neurofilament-heavy chain (pNF-H) and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes.Serum pNF-H concentrations were measured by ELISA in hospitalized patients with and without DPN (n = 118). DPN was assessed by clinical symptoms, signs, and electromyography.Compared with the non-DPN group (311.98 [189.59-634.12] pg/mL), the confirmed group (605.99 [281.17-1332.78] pg/mL) patients had the higher serum pNF-H levels (P = 0.007). DPN was significantly correlated with C-peptide (r = -0.269), total cholesterol (TC) (r = 0.185), and pNF-H (r = 0.258). Serum pNF-H levels were independently associated with DPN (P = 0.004), even after adjusting for age, sex, duration of diabetes, fasting plasma glucose, glycosylated hemoglobin A1c, TC, C-peptide, urinary albuminto/creatinine ratio, and estimated glomerular filtration rate. Compared with pNF-H quartile 1 (referent), patients in quartile 3 (odds ratio [OR], 3.977; 95% confidence interval [CI], 1.243-12.728; P = 0.021) and quartile 4 (OR, 10.488; 95% CI, 3.020-34.429; P = 0.000) had the higher risk of DPN after adjusting for the confounders.Serum pNF-H levels might be associated with the DPN, and the correlationship between serum pNF-H and DPN should be further studied.
Hastings, Mary K; Gelber, Judy R; Isaac, Elena J; Bohnert, Kathryn L; Strube, Michael J; Sinacore, David R
Foot progression angle (FPA) and duration of foot medial column loading during walking were studied in individuals with diabetes mellitus (DM), peripheral neuropathy (PN), and a forefoot ulcer (DMPN), and in age-matched control subjects. FPA was calculated from EMED-ST P-2 pressure maps as the angle formed between the longitudinal axis of the foot and the forward line of progression during walking. The medial loading duration was calculated as the amount of time the center of pressure line spent in the medial side of the foot pressure map. FPA was increased in the DMPN group, on the involved and uninvolved sides [15(9) degrees and 13(4) degrees respectively] compared the control group [9(4) degrees ]. FPA and medial loading duration were significantly correlated in the DMPN group on the involved and uninvolved sides (r>0.54, p0.82). This study provides evidence that FPA is an important biomechanical contributor to the pattern of foot loading in individuals with DM, PN, and a forefoot ulcer. Copyright 2010 Elsevier B.V. All rights reserved.
Wu, Chao; Wang, Guangbin; Zhao, Yunxia; Hao, Wen; Zhao, Lianxin; Zhang, Xinjuan; Cao, Jinfeng; Wang, Shanshan; Chen, Weibo; Chan, Queenie; Zhao, Bin; Chhabra, Avneesh
To determine the diagnostic accuracy and interobserver performance of diffusion tensor imaging (DTI) in diabetic peripheral neuropathy (DPN) and detect correlations with electrophysiology. Twelve healthy volunteers (controls) and ten DPN patients were enrolled to undergo MR examinations. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of tibial nerve (TN) and common peroneal nerve (CPN) were measured. Unpaired t test and Levene tests were performed to assess differences between the two groups. Receiver operating characteristic (ROC) analysis was performed for FA and ADC values. Pearson correlation coefficient was used to assess the correlation between DTI and electrophysiology parameters in the patient group. The FA values of TN and CPN in the DPN group were significantly lower and ADC were higher than the control group (p 0.05). Moderate diagnostic accuracy of DTI was seen in the diagnosis of DPN. DTI demonstrates moderate diagnostic accuracy and excellent interobserver performance in the detection of DPN involving the TN and CPN. There is moderate correlation with MCV. • FA values of TN and CPN are significantly lower in DPN. • ADC values of TN and CPN are significantly higher in DPN. • DTI demonstrates moderate diagnostic accuracy in detection of DPN. • There is excellent interobserver performance in DTI measurements. • Moderate correlation is seen between DTI parameters and MCV.
Shah, Kshamata M.; Mueller, Michael J.
BACKGROUND In people with diabetes and peripheral neuropathy (DM+PN), injury risk is not clearly known for weight bearing (WB) vs. non-weight bearing (NWB) exercise. In-shoe peak plantar pressures (PPP) often are used as a surrogate indicator of injury to the insensitive foot. OBJECTIVE Compare PPPs in people with DM+PN during selected WB and NWB exercises. METHODS 15 subjects with DM+PN participated. PPPs were recorded for the forefoot, midfoot, and heel during level walking and compared to; WB exercises - treadmill walking, heel and toe raises, sit to stands, stair climbing, single leg standing; and NWB exercises - stationary bicycling, balance ball exercise and plantar flexion exercise. RESULTS Compared to level walking; mean forefoot PPP during treadmill walking was 13% higher, but this difference was eliminated when walking speed was used as a covariate. Mean PPPs were similar or substantially lower for other exercises, except for higher forefoot PPP with heel raise exercises. CONCLUSIONS Slow progression and regular monitoring of insensitive feet are recommended for all exercises, but especially for heel raises, and increases in walking speed. The remaining WB and NWB exercises pose no greater risk to the insensitive foot due to increases in PPP compared to level walking. PMID:22677098
Zubairi, Ishtiaq H
Chemotherapy-induced nausea and vomiting are symptoms that cause major concern to oncology patients. This article explores the types of nausea and vomiting in the context of chemotherapy, and discusses their pathogenesis and management.
Full Text Available Introduction: Diabetic peripheral neuropathy, due to involvement of the peripheral nerves, causes muscle weakness and loss of balance in the lower extremities. Therefore, this study aimed to evaluate the effect of resistance exercise on balance and muscle strength of lower extremities in women with diabetes who suffered from peripheral neuropathy. Methods: The study population consisted of 700 diabetic patients, referring to diabetes clinic in Mashhad, Iran, out of which 20 neuropathic diabetic patients were selected and nonrandomly divided into one treatment group(n=10 and one control (n = 10 group. Static and dynamic balance were measured by the Biodex Balance and strength of the quadriceps muscles and twins were measured by the dynamometer before and after the intervention. Resistance exercise were performed three times a week for two months which, each session lasted an hour with intensity of 30 - 50% 1RM (first meeting was held with 10 repetitions and then, it was increased to 15 repetitions. SPSS statistical analysis software was applied using t-test in order to statiscally analyze the study data and the significance level was set at p &le0/05. Results: Static and dynamic balance as well as quadriceps muscle strength increased significantly in the experimental group. While the twin muscles in the control group showed a significant change (0/05&gep, no significant difference was observed in the other variables (0/05
Dzagnidze, Anna; Katsarava, Zaza; Makhalova, Julia; Liedert, Bernd; Yoon, Min-Suk; Kaube, Holger; Limmroth, Volker; Thomale, Juergen
The pronounced neurotoxicity of the potent antitumor drug cisplatin frequently results in the onset of peripheral polyneuropathy (PNP), which is assumed to be initially triggered by platination products in the nuclear DNA of affected tissues. To further elucidate the molecular mechanisms, we analyzed in a mouse model the formation and processing of the main cisplatin-induced DNA adduct (guanine-guanine intrastrand cross-link) in distinct neuronal cell types by adduct-specific monoclonal antibodies. Comparison of the adduct kinetics in cisplatin-injected mice either proficient or deficient for nucleotide excision repair (NER) functions revealed the essential role of this DNA repair pathway in protecting differentiated cells of the nervous system from excessive formation of such lesions. Hence, chronic exposure to cisplatin resulted in an accelerated accumulation of unrepaired intrastrand cross-links in neuronal cells of mice with dysfunctional NER. The augmented adduct levels in dorsal root ganglion (DRG) cells of those animals coincided with an earlier onset of PNP-like functional disturbance of their sensory nervous system. Independently from the respective repair phenotype, the amount of persisting DNA cross-links in DRG neurons at a given cumulative dose was significantly correlated to the degree of sensory impairment as measured by electroneurography. Collectively, these findings suggest a new model for the processing of cisplatin adducts in primary neuronal cells and accentuate the crucial role of effectual DNA repair capacity in the target cells for the individual risk of therapy-induced PNP.
Vegosen, Leora; Breysse, Patrick N; Agnew, Jacqueline; Gray, Gregory C; Nachamkin, Irving; Sheikh, Kazim; Kamel, Freya; Silbergeld, Ellen
Foodborne Campylobacter jejuni infection has been associated with an increased risk of autoimmune peripheral neuropathy, but risks of occupational exposure to C. jejuni have received less attention. This study compared anti-C. jejuni IgA, IgG, and IgM antibody levels, as well as the likelihood of testing positive for any of five anti-ganglioside autoantibodies, between animal farmers and non-farmers. Anti-C. jejuni antibody levels were also compared between farmers with different animal herd or flock sizes. The relationship between anti-C. jejuni antibody levels and detection of anti-ganglioside autoantibodies was also assessed. Serum samples from 129 Agricultural Health Study swine farmers (some of whom also worked with other animals) and 46 non-farmers, all from Iowa, were analyzed for anti-C. jejuni antibodies and anti-ganglioside autoantibodies using ELISA. Information on animal exposures was assessed using questionnaire data. Anti-C. jejuni antibody levels were compared using Mann-Whitney tests and linear regression on log-transformed outcomes. Fisher's Exact Tests and logistic regression were used to compare likelihood of positivity for anti-ganglioside autoantibodies. Farmers had significantly higher levels of anti-C. jejuni IgA (p antibodies compared to non-farmers. There was no consistent pattern of anti-C. jejuni antibody levels based on animal herd or flock size. A higher percentage of farmers (21%) tested positive for anti-ganglioside autoantibodies compared to non-farmers (9%), but this difference was not statistically significant (p = 0.11). There was no significant association between anti-C. jejuni antibody levels and anti-ganglioside autoantibodies. The findings provide evidence that farmers who work with animals may be at increased risk of exposure to C. jejuni. Future research should include longitudinal studies of exposures and outcomes, as well as studies of interventions to reduce exposure. Policies to reduce occupational exposure to C. jejuni
Panthi, Sharad; Jing, Xirun; Gao, Chenghan; Gao, Tianshu
Various studies have suggested the effectiveness of Chinese medicine in the treatment of diabetic peripheral neuropathy (DPN). There are several principles and methods in Chinese medicine for the treatment of DPN and yang-warming method is one of them. The purpose of this meta-analysis was to review the effectiveness and safety of yang-warming method using yang-warming Chinese medicine (YCM) in the treatment of DPN. A computer-based search of the articles from January 2001 to April 2016 with Chinese and English databases such as CNKI, CBM, Wanfang, VIP, Medline, Embase and Cochrane central register of controlled trials as well as manual search of the related articles was conducted. Randomized Controlled Trials (RCTs) comparing yang-warming Chinese medicines with western medicines in the treatment of DPN were considered for the study. The outcome measures were change in the sensory or motor nerve conduction velocity, total efficacy rate evaluated by clinical symptoms improvement, and adverse events. Two authors independently assessed the methodological quality of the included articles using Jadad scale and the twelve criteria recommended by Cochrane Back Review Group. Data were analyzed using RevMan 5.3 software provided by Cochrane collaboration. A total of 25 articles were taken for the study. Meta-analysis results showed that yang-warming Chinese medicines used in the formula alone or in combination with western medicines improved the nerve conduction velocity (NCV) in comparison to western medicines alone (p medicines alone or in combination with western medicines were apparently better than conventional western medicines in the treatment of DPN. Because of the poor quality of the reported works that were available for the present meta-analysis, it is earlier to claim the superiority of yang-warming method using YCM to western medicines for the treatment of DPN. To support these early findings, further standardized and rigorous RCTs are required.
Wang, Dong D; Bakhotmah, Balkees A; Hu, Frank B; Alzahrani, Hasan Ali
The purpose of this cross-sectional study was to investigate the prevalence and correlates of diabetic peripheral neuropathy (DPN) in a Saudi population. The study population consisted of 552 diabetic participants with an average age of 53.4 years. Among this population, 62.7% were male and 94.9% had type 2 diabetes. The average body mass index was 31.1 kg/m2. DPN was diagnosed based on a combination of reduced vibration perception measured by neurothesiometer and/or reduced light touch perception evaluated by the 10-g Semmes-Weinstein monofilament, as well as neurological symptoms. Information on socio-demographic variables, smoking status, duration of diabetes, and medications was obtained through interviews by physicians. Body weight, height, waist circumference, blood pressure and clinical markers were assessed following standard procedures. The prevalence of DPN in this population was 19.9% (95% CI, 16.7%-23.5%). In the multivariable analyses, longer duration of diabetes [odds ratio (OR) for every 5-year increase, 2.49, 95% CI, 1.75-3.53], abdominal obesity (OR, 2.53, 95% CI, 1.41-4.55), and higher levels of fasting blood glucose (OR for every 1 mmol/L increase, 1.05, 95% CI, 0.99-1.12), creatinine (OR for every 10 µmol/L increase, 1.07, 95% CI, 0.99-1.14) and white blood cell count (OR for every 106/L increase, 1.08, 95% CI, 1.01-1.16) were associated with higher odds of DPN, while oral hypoglycemic medication use was associated with a lower odds of DPN (OR, 0.47, 95% CI, 0.26-0.85). In this large Saudi population, several correlates for DPN, in addition to glycemic control and diabetes duration, were identified, including abdominal obesity, creatinine and white blood cell count.
Dong D Wang
Full Text Available The purpose of this cross-sectional study was to investigate the prevalence and correlates of diabetic peripheral neuropathy (DPN in a Saudi population. The study population consisted of 552 diabetic participants with an average age of 53.4 years. Among this population, 62.7% were male and 94.9% had type 2 diabetes. The average body mass index was 31.1 kg/m2. DPN was diagnosed based on a combination of reduced vibration perception measured by neurothesiometer and/or reduced light touch perception evaluated by the 10-g Semmes-Weinstein monofilament, as well as neurological symptoms. Information on socio-demographic variables, smoking status, duration of diabetes, and medications was obtained through interviews by physicians. Body weight, height, waist circumference, blood pressure and clinical markers were assessed following standard procedures. The prevalence of DPN in this population was 19.9% (95% CI, 16.7%-23.5%. In the multivariable analyses, longer duration of diabetes [odds ratio (OR for every 5-year increase, 2.49, 95% CI, 1.75-3.53], abdominal obesity (OR, 2.53, 95% CI, 1.41-4.55, and higher levels of fasting blood glucose (OR for every 1 mmol/L increase, 1.05, 95% CI, 0.99-1.12, creatinine (OR for every 10 µmol/L increase, 1.07, 95% CI, 0.99-1.14 and white blood cell count (OR for every 106/L increase, 1.08, 95% CI, 1.01-1.16 were associated with higher odds of DPN, while oral hypoglycemic medication use was associated with a lower odds of DPN (OR, 0.47, 95% CI, 0.26-0.85. In this large Saudi population, several correlates for DPN, in addition to glycemic control and diabetes duration, were identified, including abdominal obesity, creatinine and white blood cell count.
Schwartz, Sherwyn; Etropolski, Mila S; Shapiro, Douglas Y; Rauschkolb, Christine; Vinik, Aaron I; Lange, Bernd; Cooper, Kimberly; Van Hove, Ilse; Haeussler, Juergen
Data from two similarly designed studies of tapentadol extended release (ER) for managing neuropathic pain associated with diabetic peripheral neuropathy (DPN; NCT00455520, NCT01041859) in adults were pooled for this analysis, allowing a detailed evaluation of efficacy in patient subgroups and secondary endpoints. In each study, patients were titrated to their optimal dose of open-label tapentadol ER [100-250 mg twice daily (bid)] over 3 weeks. Patients with ≥1-point improvement in average pain intensity [11-point numerical rating scale (NRS)] were randomized (1:1) to receive placebo or tapentadol ER during a 12-week, double-blind maintenance period. Mean (standard deviation [SD]) changes in pain intensity from baseline to week 12 of maintenance in the placebo (n = 343) and tapentadol ER (n = 360) groups, respectively, were 1.28 (2.41) and 0.08 (1.87) [least squares mean difference (LSMD): -1.14 (95 % confidence interval [CI]: -1.435, -0.838); P tapentadol ER]. Significant between-group differences were also observed in changes from the start of the double-blind treatment period to the double-blind endpoint for the Short Form-36 physical functioning, role-physical, bodily pain, social functioning and role-emotional subscale and physical component summary scores, and the EuroQol 5-Dimension health status index (all P tapentadol ER). No clinically relevant differences were observed in the efficacy of tapentadol ER across patient subgroups divided by age, sex, race, opioid experience and pain intensity. Incidences of treatment-emergent adverse events were 56.0 % (192/343) with placebo and 74.7 % (269/360) with tapentadol ER during maintenance. Results of this pooled analysis indicate that tapentadol ER was effective for managing DPN-related pain, and provided consistent analgesic efficacy across different patient subgroups.
Barril, J; Estévez, J; Escudero, M A; Céspedes, M V; Níguez, N; Sogorb, M A; Monroy, A; Vilanova, E
Soluble extracts of chicken peripheral nerve contain detectable amounts of phenyl valerate esterase (PVase) activity (about 2000 nmol/min per g of fresh tissue). More than 95% of this activity is inhibited in assays where substrate has been added to a preincubated mixture of tissue with the non-neuropathic organophosphorus compound (OP) paraoxon (O,O'-diethyl p-nitrophenyl phosphate): residual activity includes soluble neuropathy target esterase (S-NTE) which, by definition, is considered resistant to long-term progressive (covalent) inhibition by paraoxon. However we have previously shown that paraoxon strongly interacts with S-NTE so interfering with its sensitivity to other inhibitors. We now show that, surprisingly, removal of paraoxon by ultrafiltration ('P' tissue) in order to avoid such an interference results in the reappearance of about 65% of total original soluble PVase activity which is inhibited in the presence of this OP. Although a purely reversible non-progressive inhibition might be suspected, kinetic analysis data show a time-progressive inhibition which suggests that such PVase(s) covalently bind paraoxon. Also a time-dependent recovery due to spontaneous reactivation of the PVase activity was observed after dilution of the inhibitor. Gel filtration chromatography of 'P' tissue in Sephacryl S-300 shows that the reactivated activity is associated with proteins of about 100-kDa mass which include S-NTE and an, as yet, unknown number of other PVases. The implications of these findings in the definition of NTE in a target tissue for the so-called organophosphorus-induced delayed polyneuropathy (OPIDP) are discussed.
Hu, Yu-Ming; Zhao, Li-Hua; Zhang, Xiu-Lin; Cai, Hong-Li; Huang, Hai-Yan; Xu, Feng; Chen, Tong; Wang, Xue-Qin; Guo, Ai-Song; Li, Jian-An; Su, Jian-Bin
Diabetic peripheral neuropathy (DPN), a common microvascular complication of diabetes, is linked to glycaemic derangements. Glycaemic variability, as a pattern of glycaemic derangements, is a key risk factor for diabetic complications. We investigated the association of glycaemic variability with DPN in a large-scale sample of type 2 diabetic patients. In this cross-sectional study, we enrolled 982 type 2 diabetic patients who were screened for DPN and monitored by a continuous glucose monitoring (CGM) system between February 2011 and January 2017. Multiple glycaemic variability parameters, including the mean amplitude of glycaemic excursions (MAGE), mean of daily differences (MODD), standard deviation of glucose (SD), and 24-h mean glucose (24-h MG), were calculated from glucose profiles obtained from CGM. Other possible risks for DPN were also examined. Of the recruited type 2 diabetic patients, 20.1% (n = 197) presented with DPN, and these patients also had a higher MAGE, MODD, SD, and 24-h MG than patients without DPN (p diabetic duration, HOMA-IR, and hemoglobin A1c (HbA1c) were found to be independent contributors to DPN, and the corresponding odds ratios (95% confidence interval) were 4.57 (3.48-6.01), 1.10 (1.03-1.17), 1.24 (1.09-1.41), and 1.33 (1.15-1.53), respectively. Receiver operating characteristic analysis indicated that the optimal MAGE cutoff value for predicting DPN was 4.60 mmol/L; the corresponding sensitivity was 64.47%, and the specificity was 75.54%. In addition to conventional risks including diabetic duration, HOMA-IR and HbA1c, increased glycaemic variability assessed by MAGE is a significant independent contributor to DPN in type 2 diabetic patients.
Full Text Available BACKGROUND: Diabetic peripheral neuropathy (DPN is very common in people with diabetes. Chinese herbal medicine (CHM therapy has been developed for DPN empirically over the years. The aim of this systematic review and meta-analysis was to assess the efficacy and safety of CHMs for patients suffering from DPN. METHODS: We performed a meta-analysis of randomized-controlled clinical trials (RCTs evaluating the efficacy and safety of CHM on DPN. Six databases were searched up to November 2012. The primary outcome measures were the absolute values or changing of motor or sensory nerve conduction velocity (NCV, and the secondary outcome measurements were clinical symptoms improvements and adverse events. The methodological quality was assessed by Jadad scale and the twelve criteria recommended by the Cochrane Back Review Group. RESULTS: One hundred and sixty-three studies claimed RCTs. Ten studies with 653 individuals were further identified based on the Jadad score ≥ 3. These 10 studies were all of high methodological quality with a low risk of bias. Meta-analysis showed the effects of NCV favoring CHMs when compared with western conventional medicines (WCM (P<0.05 or P<0.01. There is a significant difference in the total efficacy rate between the two groups (P<0.001. Adverse effects were reported in all of the ten included studies, and well tolerated in all patients with DPN. CONCLUSION: Despite of the apparently positive findings and low risk of bias, it is premature to conclude the efficacy of CHMs for the treatment of DPN because of the high clinical heterogeneity and small sample sizes of the included studies. However, CHM therapy was safe for DPN. Further standardized preparation, large sample-size and rigorously designed RCTs are required.
Wu, Shuai; Han, Yan; Hu, Qiang; Zhang, Xiaojie; Cui, Guangcheng; Li, Zezhi; Guan, Yangtai
Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T and ACE I/D polymorphisms and DPN found in various types of electronic databases. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) quality score systems were used to determine the quality of the articles selected for inclusion. Odds ratios (ORs) and its corresponding 95 % confidence interval (95 % CI) were calculated. We used STATA statistical software (version 12.0, Stata Corporation, College Station, TX, USA) to deal with statistical data. Our results indicated an association of ACE D>I mutation (OR = 1.43, 95 % CI 1.12-1.83, P = 0.004) and MTHFR 677 C>T mutation (OR = 1.43, 95 % CI 1.08-1.90, P = 0.014) with DPN under the allele model, and similar results were also found under the dominant model (all P T polymorphism may be the main risk factor for DPN in Turkey under four genetic models. ACE D>I mutation was correlated with DPN in Japanese and Pakistani populations in the majority of groups. The relationships of MTHFR 677 C>T and ACE I/D polymorphisms with DPN patients presented in this meta-analyses support the view that the MTHFR and ACE genes might play an important role in the development of DPN.
Full Text Available Elevated dynamic plantar foot pressures significantly increase the risk of foot ulceration in diabetes mellitus. The aim was to determine which factors predict plantar pressures in a population of diabetic patients who are at high-risk of foot ulceration.Patients with diabetes, peripheral neuropathy and a history of ulceration were eligible for inclusion in this cross sectional study. Demographic data, foot structure and function, and disease-related factors were recorded and used as potential predictor variables in the analyses. Barefoot peak pressures during walking were calculated for the heel, midfoot, forefoot, lesser toes, and hallux regions. Potential predictors were investigated using multivariate linear regression analyses. 167 participants with mean age of 63 years contributed 329 feet to the analyses.The regression models were able to predict between 6% (heel and 41% (midfoot of the variation in peak plantar pressures. The largest contributing factor in the heel model was glycosylated haemoglobin concentration, in the midfoot Charcot deformity, in the forefoot prominent metatarsal heads, in the lesser toes hammer toe deformity and in the hallux previous ulceration. Variables with local effects (e.g. foot deformity were stronger predictors of plantar pressure than global features (e.g. body mass, age, gender, or diabetes duration.The presence of local deformity was the largest contributing factor to barefoot dynamic plantar pressure in high-risk diabetic patients and should therefore be adequately managed to reduce plantar pressure and ulcer risk. However, a significant amount of variance is unexplained by the models, which advocates the quantitative measurement of plantar pressures in the clinical risk assessment of the patient.
Forsberg, Elisabete; Xu, Cheng; Grünler, Jacob; Frostegård, Johan; Tekle, Michael; Brismar, Kerstin; Kärvestedt, Lars
Our study aimed to explore associations between metabolic control, oxidative stress and coenzyme Q10 (CoQ10) in relation to diabetes complications in a representative population of type 2 diabetes. A geographic cohort of 156 subjects was recruited. Serum concentrations of CoQ10 and vitamin E were measured by HPLC. ROS was determined by free oxygen radicals testing (FORT). Glutaredoxin (Grx) activity, oxidized LDL cholesterol (oxLDLc), high sensitive CRP (hsCRP), HbA1c, urine albumin, serum creatinine, serum cystatin C, and plasma lipids were assayed with routine laboratory protocols. Serum CoQ10 was higher than in nondiabetics. HbA1c, fP-glucose, hyperlipidemia, inflammation (hsCRP), and increased BMI were associated with signs of oxidative stress as increased levels of FORT, Grx activity and/or increased levels of oxLDLc Oxidative stress was found to be strongly correlated with prevalence of cardiovascular disease (CVD) and peripheral sensory neuropathy (PSN). In both gender groups there were positive correlations between CoQ10 and oxLDLc, and between BMI and the ratio CoQ10/chol. Grx activity was inversely correlated to oxLDLc and CoQ10. Women with CVD and PSN had higher waist index, oxLDLc, and FORT levels compared to men but lower CoQ10 levels. Men had worse kidney function and lower vitamin E. Multiple regression analysis showed increased levels of CoQ10 to be significantly correlated with increased levels of cholesterol, triglycerides, vitamin E, fB-glucose and BMI. Hyperlipidemia, hyperglycemia and inflammation were associated with oxidative stress, which was correlated to the prevalence of diabetes complications. CoQ10 was increased in response to oxidative stress. There were gender differences in the risk factors associated with diabetes complications. Copyright © 2015 Elsevier Inc. All rights reserved.
Full Text Available Infantile Krabbe disease results in the accumulation of lipid-raft-associated galactosylsphingosine (psychosine, demyelination, neurodegeneration and premature death. Recently, axonopathy has been depicted as a contributing factor in the progression of neurodegeneration in the Twitcher mouse, a bona fide mouse model of Krabbe disease. Analysis of the temporal-expression profile of MBP (myelin basic protein isoforms showed unexpected increases of the 14, 17 and 18.5 kDa isoforms in the sciatic nerve of 1-week-old Twitcher mice, suggesting an abnormal regulation of the myelination process during early postnatal life in this mutant. Our studies showed an elevated activation of the pro-apoptotic protease caspase 3 in sciatic nerves of 15- and 30-day-old Twitcher mice, in parallel with increasing demyelination. Interestingly, while active caspase 3 was clearly contained in peripheral axons at all ages, we found no evidence of caspase accumulation in the soma of corresponding mutant spinal cord motor neurons. Furthermore, active caspase 3 was found not only in unmyelinated axons, but also in myelinated axons of the mutant sciatic nerve. These results suggest that axonal caspase activation occurs before demyelination and following a dying-back pattern. Finally, we showed that psychosine was sufficient to activate caspase 3 in motor neuronal cells in vitro in the absence of myelinating glia. Taken together, these findings indicate that degenerating mechanisms actively and specifically mediate axonal dysfunction in Krabbe disease and support the idea that psychosine is a pathogenic sphingolipid sufficient to cause axonal defects independently of demyelination.
Al-Mahroos, Faisal; Al-Roomi, Khaldoon
Although epidemiological studies have persistently shown a high prevalence of diabetes in Arabs, the control of diabetes is still poor and complications of diabetes are common. We examined the prevalence of diabetic peripheral neuropathy (DN), neuropathic foot ulceration (FU) and peripheral vascular disease (PVD), and potential risk factors for these complications among patients attending primary care diabetes clinics in Bahrain. We studied 1477 diabetic patients (Type 2 diabetes 93%); to, including 635 men and 842 women, with ages ranging from 18-75 years in a cross-sectional study. The main predictor variables were demographic and clinical data, including assessment of foot and blood parameters. Mean age of the patients and duration of diabetes were 57.3 +/- 6.32 and 9.5 +/- 8.4 years, respectively. DN was present in 36.6% of the population, FU in 5.9%, and PVD in 11.8%. Diabetic patients with neuropathy were older than patients without neuropathy (P=0.001) and had had diabetes longer (P=0.002). Diabetic patients with foot ulcers had more severe neuropathy and higher vibration perception thresholds values than patients without foot ulcers (Pobesity defined by body mass index, large waist circumference, elevated triglycerides levels and hypertension but not gender, were significant risk factors for DN in both the univariate and the multivariate analyses (P< 0.05). DN and PVD also remained significant risk factors for foot ulceration in the multiple logistic regression analysis. Rates of DN and PVD are high among diabetic patients in Bahrain. Implementation of strategies for prevention, early detection, and appropriate treatment at the primary health care level are urgently needed.
Full Text Available Oral mucositis (OM is a serious side effect of cancer chemotherapy. The pathobiology of oral mucositis remains incompletely understood due to lack of appropriate models which recapitulate the human condition. Existing rodent models are intraperitoneal and require radiation, chemical or mechanical injury to the chemotherapy protocol to induce oral lesions. We aimed to develop an OM mouse model that is induced solely by chemotherapy and reproduces macroscopic, histopathologic and inflammatory characteristics of the human condition. Female C57BL/6 mice were given intravenous 5-Fluorouracil (5-FU injections every 48 hours, for 2 weeks. A high daily dose of intraperitoneal administration was tested for comparison. Mice were monitored daily for weight loss. Epithelial histomorphometric analyses in tongue, esophageal and intestinal tissues were conducted coupled with assessment of apoptosis, cell proliferation, neutrophilic infiltration and the integrity of adherens junctions by immunohistochemistry. Neutropenia was assessed in peripheral blood and bone marrow. Tissues were analyzed for pro-inflammatory cytokines at the protein and mRNA levels. Daily intraperitoneal administration of 5-FU led to rapid weight loss and intestinal mucositis, but no oral inflammatory changes. Intravenous administration triggered atrophy of the oral and esophageal epithelium accompanied by reduction in cell proliferation and increased apoptosis. Coincidental with these changes were up-regulation of NF-κB, TNFα, IL-1β, GM-CSF, IL-6 and KC. Despite neutropenia, increased oral neutrophilic infiltration and reduced E-cadherin was observed in oroesophageal mucosae. We developed a novel experimental tool for future mechanistic studies on the pathogenesis of chemotherapy-induced OM.
Diagnosis and treatment of pain in plexopathy, radiculopathy, peripheral neuropathy and phantom limb pain. Evidence and recommendations from the Italian Consensus Conference on Pain on Neurorehabilitation.
Ferraro, Francesco; Jacopetti, Marco; Spallone, Vincenza; Padua, Luca; Traballesi, Marco; Brunelli, Stefano; Cantarella, Cristina; Ciotti, Cristina; Coraci, Daniele; Dalla Toffola, Elena; Mandrini, Silvia; Morone, Giovanni; Pazzaglia, Costanza; Romano, Marcello; Schenone, Angelo; Togni, Rossella; Tamburin, Stefano
Pain may affect all aspects of social life and reduce the quality of life. Neuropathic pain (NP) is common in patients affected by plexopathy, radiculopathy, mononeuropathy, peripheral neuropathy. Phantom limb pain (PLP) is a painful sensation that is common after amputation, and its pathophysiological mechanisms involve changes in the peripheral and central nervous system. Given the lack of conclusive evidence and specific guidelines on these topics, the aim of the Italian Consensus Conference on Pain on Neurorehabilitation (ICCPN) was to collect evidence and offer recommendations to answer currently open questions on the assessment and treatment of NP associated with the above conditions and PLP. When no evidence was available, recommendations were based on consensus between expert opinions. Current guidelines on the assessment and pharmacological treatment of NP can be applied to plexopathy, radiculopathy, mononeuropathy, peripheral neuropathy, while evidence for invasive treatments and physical therapy is generally poor because of the low quality of studies. Treatment of PLP is still unsatisfactory. Data on the functional outcome and impact of pain on neurorehabilitation outcome in these conditions are lacking. In most cases, a multidisciplinary approach is recommended to offer a better outcome and reduce side effects. High quality studies are requested to address the unmet needs in this field.
Full Text Available Objective: To analyze the effect of hyperbaric oxygen combined with 毩-lipoic acid on neurological function and serum indexes of patients with diabetic peripheral neuropathy. Methods: A total of 118 diabetic peripheral neuropathy patients who received treatment in our hospital were selected as research subjects, and according to the different clinical treatment they received, all included patients were divided into observation group 59 cases and control group 59 cases. Control group received conventional clinical treatment, and observation group received additional hyperbaric oxygen combined with 毩-lipoic acid treatment. Differences in nerve conduction velocity, gastrocnemius nerve threshold, illness-related factors, oxidative stress indicator values, and so on were compared between two groups after treatment. Results: MCV and SCV values of median nerve, ulnar nerve and tibial nerve of observation group after treatment were higher than those of control group (P<0.05; gastrocnemius nerve threshold of observation group after treatment were significantly lower than those of control group (P<0.05; serum CP and BDNF values of observation group after treatment were higher than those of control group while Cys-C, SDF-1α, HMGB1 and MBP values were lower than those of control group (P<0.05; serum MDA and NO values of observation group after treatment were lower than those of control group while SOD, CAT and GSH-Px values were higher than those of control group (P<0.05. Conclusions: Hyperbaric oxygen combined with α-lipoic acid is a good method to optimize the neurological function and improve overall illness of patients with diabetic peripheral neuropathy, and is expected to become a new way of inhibiting disease progression and improving disease outcome.
Pachman, Deirdre R; Qin, Rui; Seisler, Drew K; Smith, Ellen M L; Beutler, Andreas S; Ta, Lauren E; Lafky, Jacqueline M; Wagner-Johnston, Nina D; Ruddy, Kathryn J; Dakhil, Shaker; Staff, Nathan P; Grothey, Axel; Loprinzi, Charles L
Given that the clinical course of oxaliplatin-induced neuropathy is not well defined, the current study was performed to better understand clinical parameters associated with its presentation. Acute and chronic neuropathy was evaluated in patients receiving adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) on study N08CB (North Central Cancer Treatment Group, Alliance). Acute neuropathy was assessed by having patients complete daily questionnaires for 6 days with each cycle of FOLFOX. Before each dose of FOLFOX and as long as 18 months after chemotherapy cessation, chronic neurotoxicity was assessed with use of the 20-item, European Organisation for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy. Three hundred eight (89%) of the 346 patients had at least one symptom of acute neuropathy with the first cycle of FOLFOX; these symptoms included sensitivity to touching cold items (71%), sensitivity to swallowing cold items (71%), throat discomfort (63%), or muscle cramps (42%). Acute symptoms peaked at day 3 and improved, although they did not always resolve completely between treatments. These symptoms were about twice as severe in cycles 2 through 12 as they were in cycle 1. For chronic neurotoxicity, tingling was the most severe symptom, followed by numbness and then pain. During chemotherapy, symptoms in the hands were more prominent than they were in the feet; by 18 months, symptoms were more severe in the feet than they were in the hands. Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity (P neuropathy symptoms do not always completely resolve between treatment cycles and are only half as severe on the first cycle as compared with subsequent cycles. There is a correlation between the severities of acute and chronic neuropathies. © 2015 by American Society of Clinical Oncology.
Pelosi, Luciana; Mulroy, Eoin; Leadbetter, Ruth; Kilfoyle, Dean; Chancellor, Andrew M; Mossman, Stuart; Wing, Laurie; Wu, Teddy Y; Roxburgh, Richard H
Sensory neuronopathy is a cardinal feature of Cerebellar Ataxia Neuropathy Vestibular Areflexia Syndrome (CANVAS). Having observed that two patients with CANVAS had small median and ulnar nerves on ultrasound, we set out to examine this finding systematically in a cohort of patients with CANVAS, and compare them with both healthy controls and a cohort of patients with axonal neuropathy. We have previously reported preliminary findings in seven of these CANVAS patients and seven healthy controls. We compared the ultrasound cross-sectional area of median, ulnar, sural and tibial nerves of 14 CANVAS patients with 14 healthy controls and 14 age-and-gender matched patients with acquired primarily axonal neuropathy. We also compared the individual nerve cross-sectional areas of CANVAS and neuropathy patients with the reference values of our laboratory control population. The nerve cross-sectional area of CANVAS patients was smaller than that of both the healthy controls and the neuropathy controls, with highly significant differences at most sites (p<0.001). Conversely, the nerve cross-sectional areas in the upper limb were larger amongst neuropathy controls than healthy controls (p<0.05). On individual analysis, the ultrasound abnormality was sufficiently characteristic to be detected in all but one CANVAS patient. Small nerves in CANVAS probably reflect nerve thinning from loss of axons due to ganglion cell loss. This is distinct from the ultrasound findings in axonal neuropathy, in which nerve size was either normal or enlarged. Our findings indicate a diagnostic role for ultrasound in CANVAS sensory neuronopathy and in differentiating neuronopathy from neuropathy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Mu, Ze-Peng; Wang, Yan-Gang; Li, Cheng-Qian; Lv, Wen-Shan; Wang, Bin; Jing, Zhao-Hai; Song, Xue-Jia; Lun, Yu; Qiu, Ming-Yue; Ma, Xiao-Long
Tumor necrosis factor-α (TNF-α) is a cell signaling protein involved in systemic inflammation, and is also an important cytokine in the acute phase reaction. Several studies suggested a possible association between TNF-α and diabetic peripheral neuropathy (DPN) in type 2 diabetic patients, but no accurate conclusion was available. A systematic review and meta-analysis of observational studies was performed to comprehensively assess the association between serum TNF-α levels and DPN in type 2 diabetic patients. We searched Pubmed, Web of Science, Embase, and China Biology Medicine (CMB) databases for eligible studies. Study-specific data were combined using meta-analysis. Fourteen studies were finally included into the meta-analysis, which involved a total of 2650 participants. Meta-analysis showed that there were obviously increased serum TNF-α levels in DPN patients compared with type 2 diabetic patients without DPN (standard mean difference [SMD] = 1.203, 95 % CI 0.795-1.611, P diabetic patients with DPN when compared with healthy controls (SMD = 2.364, 95 % CI 1.333-3.394, P diabetes (odds ratio [OR] = 2.594, 95 % CI 1.182-5.500, P = 0.017). Increased serum levels of TNF-α was not associated with increased risk of painful DPN in patients with type 2 diabetes (OR = 2.486, 95 % CI 0.672-9.193, P = 0.172). Sensitivity analysis showed that there was no obvious change in the pooled estimates when omitting single study by turns. Type 2 diabetic patients with peripheral neuropathy have obviously increased serum TNF-α levels than type 2 diabetic patients without peripheral neuropathy and healthy controls, and high level of serum TNF-α may be associated with increased risk of peripheral neuropathy independently. Further prospective cohort studies are needed to assess the association between TNF-α and DPN.
Sara L. Borkosky
Full Text Available Diabetes mellitus with peripheral sensory neuropathy frequently results in forefoot ulceration. Ulceration at the first ray level tends to be recalcitrant to local wound care modalities and off-loading techniques. If healing does occur, ulcer recurrence is common. When infection develops, partial first ray amputation in an effort to preserve maximum foot length is often performed. However, the survivorship of partial first ray amputations in this patient population and associated re-amputation rate remain unknown. Therefore, in an effort to determine the actual re-amputation rate following any form of partial first ray amputation in patients with diabetes mellitus and peripheral neuropathy, the authors conducted a systematic review. Only studies involving any form of partial first ray amputation associated with diabetes mellitus and peripheral sensory neuropathy but without critical limb ischemia were included. Our search yielded a total of 24 references with 5 (20.8% meeting our inclusion criteria involving 435 partial first ray amputations. The weighted mean age of patients was 59 years and the weighted mean follow-up was 26 months. The initial amputation level included the proximal phalanx base 167 (38.4% times; first metatarsal head resection 96 (22.1% times; first metatarsal-phalangeal joint disarticulation 53 (12.2% times; first metatarsal mid-shaft 39 (9% times; hallux fillet flap 32 (7.4% times; first metatarsal base 29 (6.7% times; and partial hallux 19 (4.4% times. The incidence of re-amputation was 19.8% (86/435. The end stage, most proximal level, following re-amputation was an additional digit 32 (37.2% times; transmetatarsal 28 (32.6% times; below-knee 25 (29.1% times; and LisFranc 1 (1.2% time. The results of our systematic review reveal that one out of every five patients undergoing any version of a partial first ray amputation will eventually require more proximal re-amputation. These results reveal that partial first ray
Furukawa, S; Sakai, T; Niiya, T; Miyaoka, H; Miyake, T; Yamamoto, S; Maruyama, K; Ueda, T; Senba, H; Todo, Y; Torisu, M; Minami, H; Onji, M; Tanigawa, T; Matsuura, B; Hiasa, Y; Miyake, Y
Only limited epidemiological evidence exists regarding the relationship between diabetic neuropathy and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. To investigate the relationship between diabetic neuropathy and ED among Japanese patients with type 2 diabetes mellitus, a multicenter cross-sectional study was conducted in 287 male Japanese patients with type 2 diabetes mellitus, age (19-65 years). Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, decreased or disappeared Achilles tendon reflex and/or abnormal vibration perception. ED, moderate to severe ED, and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score diabetic neuropathy and severe ED were 47.0 and 39.0%, respectively. Diabetic neuropathy was independently positively associated with severe ED, but not ED and moderate ED: the adjusted odds ratio was 1.90 (95% confidence interval: 1.08-3.38). No relationships were found between diabetic retinopathy or diabetic nephropathy and ED. Diabetic neuropathy is positively associated with severe erectile dysfunction among Japanese type 2 diabetes mellitus patients aged <65 years.
Full Text Available Aim. To evaluate the effect of quinapril on diabetic cardiovascular autonomic neuropathy (CAN and peripheral neuropathy (DPN. Patients and Methods. Sixty-three consecutive patients with diabetes mellitus [43% males, 27 with type 1 DM, mean age 52 years (range 22–65], definite DCAN [abnormal results in 2 cardiovascular autonomic reflex tests (CARTs], and DPN were randomized to quinapril 20 mg/day (group A, n=31 or placebo (group B, n=32 for 2 years. Patients with hypertension or coronary heart disease were excluded. To detect DPN and DCAN, the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, measurement of vibration perception threshold with biothesiometer (BIO, and CARTs [R-R variation during deep breathing [assessed by expiration/inspiration ratio (E/I, mean circular resultant (MCR, and standard deviation (SD], Valsalva maneuver (Vals, 30 : 15 ratio, and orthostatic hypotension (OH] were used. Results. In group A, E/I, MCR, and SD increased (p for all comparisons < 0.05. Other indices (Vals, 30 : 15, OH, MNSIQ, MNSIE, and BIO did not change. In group B, all CART indices deteriorated, except Vals, which did not change. MNSIQ, MNSIE, and BIO did not change. Conclusions. Treatment with quinapril improves DCAN (mainly parasympathetic dysfunction. Improved autonomic balance may improve the long-term outcome of diabetic patients.
Yorek, Matthew S; Obrosov, Alexander; Shevalye, Hanna; Lupachyk, Sergey; Harper, Matthew M; Kardon, Randy H; Yorek, Mark A
We sought to determine the impact that duration of hyperglycemia and control has on corneal nerve fiber density in relation to standard diabetic neuropathy endpoints. Control and streptozotocin-diabetic C57Bl/6J mice were analyzed after 4, 8, 12, and 20 weeks. For the 20-week time point, five groups of mice were compared: control, untreated diabetic, and diabetic treated with insulin designated as having either poor glycemic control, good glycemic control, or poor glycemic control switched to good glycemic control. Hyperglycemia was regulated by use of insulin-releasing pellets. Loss of corneal nerves in the sub-epithelial nerve plexus or corneal epithelium progressed slowly in diabetic mice requiring 20 weeks to reach statistical significance. In comparison, slowing of motor and sensory nerve conduction velocity developed rapidly with significant difference compared with control mice observed after 4 and 8 weeks of hyperglycemia, respectively. In diabetic mice with good glycemic control, average blood glucose levels over the 20-week experimental period were lowered from 589 ± 2 to 251 ± 9 mg/dl. All diabetic neuropathy endpoints examined were improved in diabetic mice with good glycemic control compared with untreated diabetic mice. However, good control of blood glucose was not totally sufficient in preventing diabetic neuropathy. © 2014 Peripheral Nerve Society.
Morphological changes of the peripheral nerves evaluated by high-resolution ultrasonography are associated with the severity of diabetic neuropathy, but not corneal nerve fiber pathology in patients with type 2 diabetes.
Ishibashi, Fukashi; Taniguchi, Miki; Kojima, Rie; Kawasaki, Asami; Kosaka, Aiko; Uetake, Harumi
To evaluate the morphological changes of the median and posterior tibial nerve using high-resolution ultrasonography, and the corneal C fiber pathology by corneal confocal microscopy in type 2 diabetic patients. The cross-sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves were measured by high-resolution ultrasonography in 200 type 2 diabetic patients, stratified by the severity of diabetic neuropathy, and in 40 age- and sex-matched controls. These parameters were associated with corneal C fiber pathology visualized by corneal confocal microscopy, neurophysiological tests and severity of diabetic neuropathy. The cross-sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves in patients without diabetic neuropathy were larger than those in control subjects (P neuropathy (P neuropathy, and deteriorated only in patients with the most severe neuropathy. The association between the morphological changes of both nerves and corneal C fiber pathology was poor. The morphological changes in peripheral nerves of type 2 diabetic patients were found before the onset of neuropathy, and were closely correlated with the severity of diabetic neuropathy, but not with corneal C fiber pathology.
Juhn, Mark S; Parsons, Bruce; Varvara, Roxanna; Sadosky, Alesia
Primary care physicians face significant challenges when treating painful diabetic peripheral neuropathy (pDPN). The physician must determine the best dosing strategy, consider the use of combination therapy, and decide how best to treat patients who have responded poorly to other treatment options in the past. With a focus on these issues, this paper will review the use of pregabalin for the treatment of pDPN in order to provide physicians with clinical data needed to develop, in combination with real-world prescribing data, effective treatment strategies for this common but challenging type of pain. A formal PubMed search, along with a search of unpublished data from the Pfizer clinical trial database, was used to identify papers describing results from clinical trials of pregabalin in patients with pDPN. Papers were selected for inclusion in the review if they addressed the use of pregabalin in the context of a head-to-head treatment comparison, use in refractory patients, or as part of combination therapy. A discussion of pregabalin dosing and adverse events is also presented. There is some difference with respect to the maximum approved dose of pregabalin for the treatment of pDPN in the United States (300 mg/day) and European Union (600 mg/day), though clinical data demonstrate that pregabalin doses >300 mg/day may be beneficial in some patients. Pregabalin has shown efficacy (and is approved) as a monotherapy for pDPN, although several guidelines recommend combination therapy for challenging cases. However, evidence to support combination therapy is sparse and the decision of monotherapy vs. combination therapy should be at the physician's discretion. There are data demonstrating the efficacy of pregabalin in some patients with pDPN who have not responded to other pharmacological treatments, including those unresponsive to treatment with gabapentin. Clinical guidelines acknowledge the paucity of head-to-head data among treatment options, but
Full Text Available Foodborne Campylobacter jejuni infection has been associated with an increased risk of autoimmune peripheral neuropathy, but risks of occupational exposure to C. jejuni have received less attention. This study compared anti-C. jejuni IgA, IgG, and IgM antibody levels, as well as the likelihood of testing positive for any of five anti-ganglioside autoantibodies, between animal farmers and non-farmers. Anti-C. jejuni antibody levels were also compared between farmers with different animal herd or flock sizes. The relationship between anti-C. jejuni antibody levels and detection of anti-ganglioside autoantibodies was also assessed.Serum samples from 129 Agricultural Health Study swine farmers (some of whom also worked with other animals and 46 non-farmers, all from Iowa, were analyzed for anti-C. jejuni antibodies and anti-ganglioside autoantibodies using ELISA. Information on animal exposures was assessed using questionnaire data. Anti-C. jejuni antibody levels were compared using Mann-Whitney tests and linear regression on log-transformed outcomes. Fisher's Exact Tests and logistic regression were used to compare likelihood of positivity for anti-ganglioside autoantibodies.Farmers had significantly higher levels of anti-C. jejuni IgA (p < 0.0001 and IgG (p = 0.02 antibodies compared to non-farmers. There was no consistent pattern of anti-C. jejuni antibody levels based on animal herd or flock size. A higher percentage of farmers (21% tested positive for anti-ganglioside autoantibodies compared to non-farmers (9%, but this difference was not statistically significant (p = 0.11. There was no significant association between anti-C. jejuni antibody levels and anti-ganglioside autoantibodies.The findings provide evidence that farmers who work with animals may be at increased risk of exposure to C. jejuni. Future research should include longitudinal studies of exposures and outcomes, as well as studies of interventions to reduce exposure. Policies to
Full Text Available 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.
Coppey, Lawrence J; Davidson, Eric P; Obrosov, Alexander; Yorek, Mark A
The purpose of this study was to determine the effect of supplementing the diet of type 1 diabetic rats with menhaden oil on diabetic neuropathy. Menhaden oil is a natural source for n-3 fatty acids, which have been shown to have beneficial effects in cardiovascular disease and other morbidities. Streptozotocin-induced diabetic rats were used to examine the influence of supplementing their diet with 25% menhaden oil on diabetic neuropathy. Both prevention and intervention protocols were used. Endpoints included motor and sensory nerve conduction velocity, thermal and mechanical sensitivity, and innervation and sensitivity of the cornea and hindpaw. Diabetic neuropathy as evaluated by the stated endpoints was found to be progressive. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels. Diabetic rats at 16-wk duration were thermal hypoalgesic and had reduced motor and sensory nerve conduction velocities, and innervation and sensitivity of the cornea and skin were impaired. These endpoints were significantly improved with menhaden oil treatment following the prevention or intervention protocol. We found that supplementing the diet of type 1 diabetic rats with menhaden oil improved a variety of endpoints associated with diabetic neuropathy. These results suggest that enriching the diet with n-3 fatty acids may be a good treatment strategy for diabetic neuropathy.
Laping, Nicholas J; DeMartino, Michael P; Cottom, Joshua E; Axten, Jeffrey M; Emery, John G; Guss, Jeffrey H; Burman, Miriam; Foley, James J; Cheung, Mui; Oliff, Allen; Kumar, Sanjay
Neutropenia is a common consequence of radiation and chemotherapy in cancer patients. The resulting immunocompromised patients become highly susceptible to potentially life-threatening infections. Granulocyte colony-stimulating factor (G-CSF) is known to stimulate neutrophil production and is widely used as a treatment of chemotherapy-induced neutropenia. A small-molecule G-CSF secretagogue without a requirement for refrigerated supply chain would offer a more convenient and cost-effective treatment of chemotherapy-induced neutropenia. Bacterial lipopeptides activate innate immune responses through Toll-like receptor 2 (TLR2) and induce the release of cytokines, including G-CSF, from macrophages, monocytes, and endothelial. Pam2CSK4 is a synthetic lipopeptide that effectively mimics bacterial lipoproteins known to activate TLR2 receptor signaling through the TLR2/6 heterodimer. Substrate-based drug design led to the discovery of GSK3277329, which stimulated the release of G-CSF in activated THP-1 cells, peripheral blood mononuclear cells, and human umbilical vein endothelial cells. When administered subcutaneously to cynomolgus monkeys (Macaca fascicularis), GSK3277329 caused systemic elevation of G-CSF and interleukin-6 (IL-6), but not IL-1β or tumor necrosis factor α, indicating a selective cytokine-stimulation profile. Repeat daily injections of GSK3277329 in healthy monkeys also raised circulating neutrophils above the normal range over a 1-week treatment period. More importantly, repeated daily injections of GSK3277329 over a 2-week period restored neutrophil loss in monkeys given chemotherapy treatment (cyclophosphamide, Cytoxan). These data demonstrate preclinical in vivo proof of concept that TLR2 agonism can drive both G-CSF induction and subsequent neutrophil elevation in the cynomolgus monkey and could be a therapeutic strategy for the treatment of chemotherapy-induced neutropenia.
The review concentrates on the use of clinical neurophysiology in peripheral nerve disorders covered in the present issue. It is pertinent to distinguish different types of involvement of fibers in diabetic neuropathy, including the involvement of small and large fibers, to outline the diagnostic...... criteria of inflammatory neuropathies, and to describe the spectrum of peripheral nerve pathophysiology in inherited neuropathies. Painful neuropathies represent a particular challenge to clinical neurophysiology since it is mainly small fibers, which are difficult to study, that are affected....
Lechleitner, Monika; Abrahamian, Heidemarie; Francesconi, Claudia; Kofler, Markus
These are the guidelines for diagnosis and treatment of diabetic neuropathy. This diabetic late complication comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy. The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided.
Toyama, Satoshi; Shimoyama, Naohito; Shimoyama, Megumi
Orexins are neuropeptides that are localized to neurons in the lateral and dorsal hypothalamus but its receptors are distributed to many different regions of the central nervous system. Orexins are implicated in a variety of physiological functions including sleep regulation, energy homeostats, and stress reactions. Furthermore, orexins administered exogenously have been shown to have analgesic effects in animal models. A type of intractable pain in patients is pain due to chemotherapy-induced peripheral neuropathy (CIPN). Several chemotherapeutic agents used for the treatment of malignant diseases induce dose-limiting neuropathic pain that compromises patients' quality of life. Here, we examined the analgesic effect of orexin-A in a murine model of CIPN, and compared it with the effect of duloxetine, the only drug recommended for the treatment of CIPN pain in patients. CIPN was induced in male BALB/c mice by repeated intraperitoneal injection of oxaliplatin, a platinum chemotherapeutic agent used for the treatment of advanced colorectal cancer. Neuropathic mechanical allodynia was assessed by the von Frey test, and the effect on acute thermal pain was assessed by the tail flick test. Intracerebroventricularly administered orexin-A dose-dependently attenuated oxaliplatin-induced mechanical allodynia and increased tail flick latencies. Oxaliplatin-induced mechanical allodynia was completely reversed by orexin-A at a low dose that did not increase tail flick latency. Duloxetine only partially reversed mechanical allodynia and had no effect on tail flick latency. The analgesic effect of orexin-A on oxaliplatin-induced mechanical allodynia was completely antagonized by prior intraperitoneal injection of SB-408124 (orexin type-1 receptor antagonist), but not by prior intraperitoneal injection of TCS-OX2-29 (orexin type-2 receptor antagonist). Our findings suggest that orexin-A is more potent than duloxetine in relieving pain CIPN pain and its analgesic effect is
Arenas-Pinto, Alejandro; Thompson, Jennifer; Musoro, Godfrey; Musana, Hellen; Lugemwa, Abbas; Kambugu, Andrew; Mweemba, Aggrey; Atwongyeire, Dickens; Thomason, Margaret J; Walker, A Sarah; Paton, Nicholas I
Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22% at entry (N = 1,251) and was associated (p therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.
García-Sanz, Ramón; Corchete, Luis Antonio; Alcoceba, Miguel; Chillon, María Carmen; Jiménez, Cristina; Prieto, Isabel; García-Álvarez, María; Puig, Noemi; Rapado, Immaculada; Barrio, Santiago; Oriol, Albert; Blanchard, María Jesús; de la Rubia, Javier; Martínez, Rafael; Lahuerta, Juan José; González Díaz, Marcos; Mateos, María Victoria; San Miguel, Jesús Fernando; Martínez-López, Joaquín; Sarasquete, María Eugenia
Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment. Copyright © 2016 John Wiley & Sons, Ltd.
Floortje van Nooten
Full Text Available Background. The Self-Assessment of Treatment version II (SAT II measures treatment-related improvements in pain and impacts and impressions of treatment in neuropathic pain patients. The measure has baseline and follow-up versions. This study assesses the measurement properties of the SAT II. Methods. Data from 369 painful diabetic peripheral neuropathy (PDPN patients from a phase III trial assessing capsaicin 8% patch (Qutenza® efficacy and safety were used in these analyses. Reliability, convergent validity, known-groups validity, and responsiveness (using the Brief Pain Inventory-Diabetic Neuropathy [BPI-DN] and Patient Global Impression of Change [PGIC] analyses were conducted, and minimally important differences (MID were estimated. Results. Exploratory factor analysis supported a one-factor solution for the six impact items. The SAT II has good internal consistency (Cronbach’s alpha: 0.96 and test-retest reliability (intraclass correlation coefficients: 0.62–0.88. Assessment of convergent validity showed moderate to strong correlations with change in other study endpoints. Scores varied significantly by level of pain intensity and sleep interference (p<0.05 defined by the BPI-DN. Responsiveness was shown based on the PGIC. MID estimates ranged from 1.2 to 2.4 (pain improvement and 1.0 to 2.0 (impact scores. Conclusions. The SAT II is a reliable and valid measure for assessing treatment improvement in PDPN patients.
Zangiabadi, Nasser; Asadi-Shekaari, Majid; Sheibani, Vahid; Jafari, Mandana; Shabani, Mohammad; Asadi, Ali Reza; Tajadini, Hale; Jarahi, Morteza
Background. To study the effects of an aqueous extract of date fruit (Phoenix dactylifera L. Arecaceae) diet on diabetic polyneuropathy (DPN) in streptozotocin- (STZ-) induced diabetic rats. Methods. The effects of a date fruit extract (DFE) diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with a nondiabetic control group, diabetic control group (sham), and vehicle group with respect to the following parameters: open field behavioral test, motor nerve conduction velocity (MNCV), and morphological observations. Results. In the model of STZ-induced of diabetic neuropathy, chronic treatment for 6 weeks with DFE counteracted the impairment of the explorative activity of the rats in an open field behavioral test and of the conduction velocity of the sciatic nerve (MNCV). In addition, pretreatment with DFE significantly reversed each nerve diameter reduction in diabetic rats. Conclusion. DFE treatment shows efficacy for preventing diabetic deterioration and for improving pathological parameters of diabetic neuropathy in rats, as compared with control groups. PMID:22191015
Stagg, Nicola J; Shen, Ben-Quan; Brunstein, Flavia; Li, Chunze; Kamath, Amrita V; Zhong, Fiona; Schutten, Melissa; Fine, Bernard M
Antibody drug conjugates (ADC) consist of potent cytotoxic drugs conjugated to antibodies via chemical linkers, which enables specific targeting of tumor cells while reducing systemic exposure to the cytotoxic drug and improving the therapeutic window. The valine citrulline monomethyl auristatin E (vcMMAE, conventional linker-drug) ADC platform has shown promising clinical activity in several cancers, but peripheral neuropathy (PN) is a frequent adverse event leading to treatment discontinuation and dose reduction. This was not predicted based on nonclinical toxicology studies in monkeys or rats treated with vcMMAE ADCs. We evaluated four hypotheses for the lack of translatability of PN with vcMMAE ADCs: 1) species differences in exposure; 2) insensitivity of animal models; 3) species differences in target biology and other vcMMAE ADC properties in peripheral nerves and 4) increased susceptibility of patient population. The result of this hypothesis-based approach identified opportunities to improve the predictivity of PN in our animal models by increasing duration of exposure and adding an expanded neurohistopathology assessment of peripheral nerves. The utility of a predictive animal model would be to provide possible mitigation strategies in the clinic with vcMMAE ADCs and help to screen the next generation microtubule inhibitor (MTI) ADCs for reduced PN. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Wiethoff, Sarah; Xiromerisiou, Georgia; Bettencourt, Conceição; Kioumi, Anna; Tsiptsios, Iakovos; Tychalas, Athanasios; Evaggelia, Markousi; George, Kaltsounis; Makris, Vasileios; Hardy, John; Houlden, Henry
We present a 70-year-old male patient of Greek origin with choreatic movements of the tongue and face, lower limb muscle weakness, peripheral neuropathy, elevated creatinephosphokinase (CPK), acanthocytosis and haemolysis in the absence of Kell RBC antigens with an additional Factor IX-deficiency. Genetic testing for mutations in the three exons of the XK gene revealed a previously unreported hemizygous single base-pair frameshift deletion at exon 1 (c.229delC, p.Leu80fs). In conclusion, we hereby describe a rare phenotype of a patient with McLeod syndrome which was discovered coincidentally during routine blood group testing and consecutively genetically confirmed. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Neuropathy - metabolic ... damage can be caused by many different things. Metabolic neuropathy may be caused by: A problem with ... is one of the most common causes of metabolic neuropathies. People who are at the highest risk ...
Sharma, Supriya; Sharma, Pallavi; Kulurkar, Pankaj; Singh, Damanpreet; Kumar, Dinesh; Patial, Vikram
Picrorhiza kurroa Royle (Scrophulariaceae) is an important medicinal herb being widely used in variety of ailments. The present study was envisaged to evaluate the effects of iridoid glycosides enriched fraction (IGs) from Picrorhiza kurroa rhizome against cyclophosphamide (CP) -induced renal toxicity and peripheral neuropathy. Mice in different groups were pretreated with 25, 50 and 100 mg/kg; p.o. doses of IGs for 21 days, followed by cyclophosphamide intoxication for consecutive two days. Further, to identify the putative role of PPAR-γ receptors for the protective effect of IGs, an additional group of mice were pretreated with PPAR-γ antagonist BADGE (5 mg/kg; i.p.) followed by IGs (100 mg/kg; p.o.) for 21 days before CP intoxication. IGs pretreatment decreased the hyperalgesic responses toward acetone and heat in acetone drop and tail immersion tests. The abolition of intramyelin odema, cytoplasmic vacuolization and axonal degeneration of sciatic nerve were observed in IGs pretreated mice in a dose-dependent manner. IGs treatment also attenuated the altered serum biochemical markers for renal injury. Furthermore, the treatment prevented renal tubular swelling, granular degeneration and glomerular damage. The levels of IL-1β and TNFα in different group revealed the anti-inflammatory effect of IGs, which was further confirmed by improvement in altered expressions of NF-kB in kidney and sciatic serve. Bax/Bcl-2 expressions and caspase 3/9 activity in renal tissues showed the anti-apoptotic effect of IGs. IGs pretreatment also improved the PPAR-γ expression in the kidney tissues. All the observed protective effects of IGs were suppressed after pretreatment with BADGE. Present study concludes that IGs from Picrorhiza kurroa attenuates CP-induced renal toxicity and peripheral neuropathy via PPAR-γ -mediated pathways. Copyright © 2017 Elsevier GmbH. All rights reserved.
Full Text Available Introduction: Chronic peripheral neuropathic pain (CPNP is a condition due to peripheral nervous system diseases or injury, but its prevalence is unknown in Italian primary care. Aim: The aim of this study is to assess the prevalence of CPNP in a rural primary care area in Northern Italy. Materials and Methods: A multicenter audit study was carried out in a rural area in Northern Italy with 113 participating general practitioners (GPs seeing 58,480 patients> 18 years during 3 months. Patients who for any reason attended GPs' surgeries and had symptoms suggestive of neuropathic pain (NP were given the NP diagnostic questionnaire “Douleur Neuropathique en 4 Questions” (DN4 and recorded their pain level on a visual analog scale (VAS. Results: Chronic NP was established by a DN4 score of ≥4 and a VAS pain score of ≥40 mm for> 6 months together with a clinical diagnosis in 448 (254 women and 194 men out of 58,480 patients giving a prevalence of 0.77%. 179 patients (0.31% had diabetes neuropathy, 142 (0.24% had postherpetic pain, 41 (0.07% had trigeminal neuralgia, 27 (0.05% had NP postinjury, 27 (0.05% had NP caused by nerve entrapments, 11 (0.02% had NP triggered by systemic diseases, and 21 (0.04% had NP of unknown etiology. Conclusions: The prevalence of CPNP in this population of primary care attenders in a rural area in Northern Italy was 0.77%. Diabetes neuropathy (0.31% and postherpetic pain (0.24% were the two most common subgroups of NP, followed by trigeminal neuralgia (0.07%.
Full Text Available Peripheral neuropathies affect children more often than the young and middle age adults, but less frequently than the elderly. They differ from those in the adults because of the high incidence of hereditary neuropathies, including those associated with metabolic and degenerative disorders of the central nervous system; the low incidence of toxic neuropathies and those associated with systemic disorders; and a lower incidence of chronic acquired polineuropathies. Nerve biopsies are indicated if the diagnosis has not been made with clinical and electrophysiologic studies and other methods, and should only be performed in laboratories with appropriate techniques for the study of the nerve. It is important to know the normal development of the nerve, the thickness of the myelin sheath and the distribution of small and large fibers, according to the age. The main morphological aspects of the most frequent neuropathies in children - acquired (inflammatory, demyelinating and hereditary (sensory-motor, sensory-autonomic, ataxic, and those associated with metabolic and degenerative disorders, are reviewed.As neuropatias periféricas afetam as crianças mais frequentemente do que os adultos jovens e de meia idade, mas menos frequentemente do que os mais velhos. Diferem das dos adultos pela alta incidência de neuropatias hereditárias, incluindo as associadas a doenças metabólicas e degenerativas do sistema nervoso central; pela baixa incidência de neuropatias tóxicas e associadas a doenças sistêmicas; e pela menor incidência de polineuropatias crônicas adquiridas. As biópsias de nervo são indicadas se o diagnóstico não for feito com estudos clínicos, eletrofisiológicos e outros métodos de investigação, e só devem ser realizadas em laboratórios que dispõem de técnicas apropriadas para estudo do nervo. É importante conhecer o desenvolvimento do nervo periférico, a espessura da mielina e a distribuição das fibras quanto ao calibre
This article provides insight into the growth cycle of a hair follicle and the potential impact chemotherapy agents can have on this process, which often results in hair loss (alopecia). It explores the psychological consequences of chemotherapy-induced alopecia for an individual as a result of the perceptions of others as well as an individual's perception of his or her self-image. Despite the development of various forms of scalp cooling, chemotherapy-induced alopecia remains a major side effect for patients receiving chemotherapy; however, there have been improvements in wig provision and changing public opinion relating to baldness. Although chemotherapy-induced alopecia affects both males and females and all age groups, this article focuses on the potential impact for patients receiving chemotherapy as a form of treatment for breast cancer. As professionals we need to understand the social significance of hair in relation to a person's outward presentation and social interactions, along with the possible psychological implications of a person losing his or her bodily hair, and not just the head hair. We must aim to minimize the distress alopecia can cause by: ensuring we provide patients with up-to-date verbal and written information to enable them to prepare for losing their hair; helping them to preserve their self-image and minimize the psychological consequences of hair loss while receiving chemotherapy; and preparing them for their hair re-growth following completion of chemotherapy.
Full Text Available Peripheral neuropathy is a common neurological complication occurring in asymptomatic and symptomatic stages of HIV infection. The most common syndromes are distal symmetric polyneuropathy, inflammatory demielinating polyneuropathy, poliradiculopathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy. PURPOSE: To evaluate the frequency of peripheral neuropathy in a group of HIV seropositive outpatients in São Paulo, Brazil. METHOD: Over a period of 17 months, 49 HIV+ patients where evaluated clinically. Laboratory analysis and electroneuromyography were requested to all patients. RESULTS: >Thirty four (69.4% of the 49 patients had the diagnosis of peripheral neuropathy established on clinical grounds. The most common sign was impairment (97.1% of sensibility. Thirteen (33.3% of the 39 that were subjected to electroneuromyography had features of peripheral neuropathy, being a sensitive-motor axonal neuropathy the most common. No abnormalities were found in the laboratory analysis performed in 42 patients, except in four who had VDRL positive. CONCLUSION: A peripheral neuropathy was frequently found upon clinical examination in our group of HIV positive individuals.A neuropatia periférica é complicação neurológica comum, podendo ocorrer nas fases assintomáticas e sintomáticas da infecção pelo vírus da imunodeficiência humana (HIV. As síndromes mais comuns são a polineuropatia distal simétrica, polineuropatia desmielinizante inflamatória, polirradiculopatia, mononeuropatia, mononeuropatia múltipla e neuropatia autonômica. OBJETIVO: Avaliar a freqüência da neuropatia periférica em um grupo de pacientes HIV positivo em São Paulo, Brasil. MÉTODO: Em um período de 17 meses, foram avaliados clinicamente 49 pacientes HIV positivos. Foram solicitados exames laboratoriais e eletroneuromiografia (ENMG para todos os pacientes. RESULTADOS: Foi estabelecido o diagnóstico clínico de neuropatia periférica em 34 (69
MRI in the study of distal primary myopathopies and of muscular alterations due to peripheral neuropathies: possible diagnostic capacities of MR equipment with low intensity field (0.2 T) dedicated to peripheral limbs.
Messineo, D; Cremona, A; Trinci, M; Francia, A; Marini, A
The purpose of this work was to investigate whether or not an magnetic resonance imaging (MRI) equipment with a low field intensity (0.2 T) used in the study of muscular alterations can diagnose primary or secondary myopathies, due to peripheral neuropathies. In this study the peripheral areas of all patients were examined. A total of 40 patients (23 males and 17 females) were tested. Their age ranged from 10 to 78 years age (mean age 40.8, SD +/- 19,45 years). The group includes 23 patients: 18 with Stainert Myotonic Distrophy, 5 were myositic, and the remaining 17 had peropheral neuropathies. Every patient received a clinic examination, followed by EMG and MRI. The MRI study was done with a system dedicated to the study of limbs (Artoscan, Esaote Biomedica) that used a 0.2 T permanent magnet. Spin-echo T1, T2-weighted, multiple-echo, and STIR sequences were used. A good correspondence was found between clinical and MRI data. Specifically, in the group of 23 myopathies, Sperman's index was found to be 0.80 in its correlation between the clinical examination and MRI; in the group of 17 myopathies it was found to be 0.63. A discrepancy was found among clinical examination, EMG, and MRI in patients with neuropathies who were showing a lack of myelin and mixed ones. The T2-weighted and STIR sequences had great sensitivity in showing initial changes in the muscles. The SE T1-weighted sequence was especially useful in detecting degeneration in the fibrous adipose tissue. The STIR sequence because of its high sensitivity and greater speed of response could be used instead of the SE T2 weighted particularly in the study of patients, who were noted to tolerate a prolonge period of scanning. However, because these sequences have a low signal noise ratio, they must always be associated with a SE sequence, whenever there would be need of a precise determination of the structures under study. The MRI low field intensity was also found to be a useful technique in screening
Muncey, Aaron R; Saulles, Adam R; Koch, Lauren G; Britton, Steven L; Baghdoyan, Helen A; Lydic, Ralph
Sleep apnea, hypertension, atherosclerosis, and obesity are features of metabolic syndrome associated with decreased restorative sleep and increased pain. These traits are relevant for anesthesiology because they confer increased risks of a negative anesthetic outcome. This study tested the one-tailed hypothesis that rats bred for low intrinsic aerobic capacity have enhanced nociception and disordered sleep. Rats were developed from a breeding strategy that selected for low aerobic capacity runners (LCR) and high aerobic capacity runners (HCR). Four phenotypes were quantified. Rats underwent von Frey sensory testing (n = 12), thermal nociceptive testing (n = 12), electrographic recordings of sleep and wakefulness (n = 16), and thermal nociceptive testing (n = 14) before and for 6 weeks after a unilateral chronic neuropathy of the sciatic nerve. Paw withdrawal latency to a thermal nociceptive stimulus was significantly (P obesity might confer increased risks for anesthesia.
Moldovan, Mihai; Pinchenko, Volodymyr; Dmytriyeva, Oksana; Pankratova, Stanislava; Fugleholm, Kåre; Klingelhofer, Jorg; Bock, Elisabeth; Berezin, Vladimir; Krarup, Christian; Kiryushko, Darya
We recently found that S100A4, a member of the multifunctional S100 protein family, protects neurons in the injured brain and identified two sequence motifs in S100A4 mediating its neurotrophic effect. Synthetic peptides encompassing these motifs stimulated neuritogenesis and survival in vitro and mimicked the S100A4-induced neuroprotection in brain trauma. Here, we investigated a possible function of S100A4 and its mimetics in the pathologies of the peripheral nervous system (PNS). We found that S100A4 was expressed in the injured PNS and that its peptide mimetic (H3) affected the regeneration and survival of myelinated axons. H3 accelerated electrophysiological, behavioral and morphological recovery after sciatic nerve crush while transiently delaying regeneration after sciatic nerve transection and repair. On the basis of the finding that both S100A4 and H3 increased neurite branching in vitro, these effects were attributed to the modulatory effect of H3 on initial axonal sprouting. In contrast to the modest effect of H3 on the time course of regeneration, H3 had a long-term neuroprotective effect in the myelin protein P0 null mice, a model of dysmyelinating neuropathy (Charcot-Marie-Tooth type 1 disease), where the peptide attenuated the deterioration of nerve conduction, demyelination and axonal loss. From these results, S100A4 mimetics emerge as a possible means to enhance axonal sprouting and survival, especially in the context of demyelinating neuropathies with secondary axonal loss, such as Charcot-Marie-Tooth type 1 disease. Moreover, our data suggest that S100A4 is a neuroprotectant in PNS and that other S100 proteins, sharing high homology in the H3 motif, may have important functions in PNS pathologies.
Swislocki, Arthur; Orth, Marla; Bales, Maurice; Weisshaupt, Jennifer; West, Claudia; Edrington, Janet; Cooper, Bruce; Saputo, Len; Islas, Melissa; Miaskowski, Christine
Peripheral neuropathy is one of the most common complications of diabetes. The purpose of this study was to evaluate the effects of photon stimulation on pain intensity, pain relief, pain qualities, sensation and quality of life (QOL) in patients with painful diabetic peripheral neuropathy. In this randomized, placebo-controlled trial, patients were assigned to receive either four photon stimulations (n=63) or four placebo (n=58) treatments. Pain intensity, pain relief, and pain qualities were assessed using self-report questionnaires. Sensation was evaluated using monofilament testing. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36). Multilevel regression model analyses were used to evaluate between-group differences in study outcomes. No differences, over time, in any pain intensity scores (i.e., pain intensity immediately post-treatment, average pain, worst pain) or pain relief scores were found between the placebo and treatment groups. However, significant decreases, over time, were found in some pain quality scores, and significant improvements in sensation were found in patients who received the photon stimulation compared with placebo. In addition, patients in the treatment group reported significant improvements in SF-36 social functioning and mental health scores. Findings from a responder analysis demonstrated that no differences were found in the percentages of patients in the placebo and treatment groups who received 30% or more or 50% or more reduction in pain scores immediately post-treatment. However, significant differences were found in the distribution of the changes in pain relief scores, with most of the patients in the photon stimulation group reporting a slight (28.6%) to moderate (34.9%) improvement in pain relief from the beginning to the end of the study compared with no change in pain relief (43.1%) in the placebo group. Four treatments with photon stimulation resulted in significant improvements in some pain
Okada, Naoto; Hanafusa, Takeshi; Sakurada, Takumi; Teraoka, Kazuhiko; Kujime, Toshihide; Abe, Masahiro; Shinohara, Yasuo; Kawazoe, Kazuyoshi; Minakuchi, Kazuo
Background Peripheral neuropathy is a well-known side effect of vincristine (VCR), a microtubule inhibitor used for R-CHOP or R-CHOP-like (namely R-CVP and R-THP-COP) regimens. Previous studies have shown that both the total dose of VCR and the number of treatment cycles are related to the incidence of VCR-induced peripheral neuropathy (VIPN). However, VIPN will also occur during the first treatment cycle regardless of the total dose of VCR or number of treatment cycles (early-onset VIPN). There is little information about early-onset VIPN, and it is difficult to predict. The present study’s goal was to identify risk factors for early-onset VIPN. Methods We analyzed the case records of patients who had their first administration of an R-CHOP or R-CHOP-like regimen between April 2008 and August 2013 at Tokushima University Hospital in Tokushima, Japan. To identify the risk factors for early-onset VIPN, we performed univariate and multivariate logistic regression analyses. Results Forty-one patients underwent an R-CHOP or R-CHOP-like regimen for the first time at Tokushima University Hospital between April 2008 and August 2013, and 14 patients had grade 1 or higher early-onset VIPN. A univariate analysis revealed that age, the dose of VCR and the concomitant use of aprepitant appeared to be the risk factors of early-onset VIPN. In our calculation using receiver-operator characteristics curves, the cut-off value for patient age was 65 years and that of the dose of VCR was 1.9 mg. A multivariate analysis revealed that VCR dose ≥ 1.9 mg and the concomitant use of the antiemetic aprepitant were independent risk factors for early-onset VIPN. Conclusions Our present study showed that the patients who had VCR dose ≥ 1.9 mg and the concomitant use of aprepitant had the risk for early-onset VIPN. This suggests that it is important to use aprepitant in light of the risk of early-onset VIPN and the benefit of aprepitant’s antiemetic effect in R-CHOP and R
Jung, Yongjae; Lee, Ji Hwan; Kim, Woojin; Yoon, Sang Hyub; Kim, Sun Kwang
Oxaliplatin, a widely used anticancer drug against metastatic colorectal cancer, can induce acute peripheral neuropathy, which is characterized by cold and mechanical allodynia. Activation of glial cells (e.g. astrocytes and microglia) and increase of pro-inflammatory cytokines (e.g. IL-1β and TNF-α) in the spinal cord play a crucial role in the pathogenesis of neuropathic pain. Our previous study demonstrated that Gyejigachulbu-Tang (GBT), a herbal complex formula, alleviates oxaliplatin-induced neuropathic pain in rats by suppressing spinal glial activation. However, it remains to be elucidated whether and how Buja (Aconiti Tuber), a major ingredient of GBT, is involved in the efficacy of GBT. Cold and mechanical allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) in Sprauge-Dawley rats were evaluated by a tail immersion test in cold water (4 °C) and a von Frey hair test, respectively. Buja (300 mg/kg) was orally administrated for five consecutive days after the oxaliplatin injection. Glial activation in the spinal cord was quantified by immunohistochemical staining using GFAP (for astrocytes) and Iba-1 (for microglia) antibodies. The amount of spinal pro-inflammatory cytokines, IL-1β and TNF-α, were measured by ELISA. Significant behavioral signs of cold and mechanical allodynia were observed 3 days after an oxaliplatin injection. Oral administration of Buja significantly alleviated oxaliplatin-induced cold and mechanical allodynia by increasing the tail withdrawal latency to cold stimuli and mechanical threshold. Immunohistochemical analysis showed the activation of astrocytes and microglia and the increase of the IL-1β and TNF-α levels in the spinal cord after an oxaliplatin injection. Administration of Buja suppressed the activation of spinal astrocytes without affecting microglial activation and down-regulated both IL-1β and TNF-α levels in the spinal cord. Our results indicate that Buja has a potent anti-allodynic effect in a rat
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
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
Hassan Khan, Imran; Anwar, Shahzad; Hanif, Asif; Ayub, Muhammad; Jamil Raja, Arsalan
Background: Painful neuropathy is a very common complication in diabetic patients. Various treatment strategies like manual therapies, conservative management, drug therapy and exercise have been opted for this problem. Studies have shown clinical effectiveness of laser acupuncture as well. On the other hand, Amitryptaline is also a commonly used treatment for this disease. We aim to compare the efficacy of both treatments. Objective: To assess the effect of laser acupuncture in patients suffering from painful diabetic neuropathy and its comparison with standard of care. Patients and Method: This study was conducted in Diabetic and Endocrine Management Center (DEMC) Lahore General Hospital, Lahore, Pakistan. A randomized control trial (RCT) was opted and a total of 164 patients were chosen using Non-probability purposive sampling technique. Pain was graded by using a patient friendly Visual Analogue Score (VAS), scoring from 0 to 10. Treatment was done involving organized fortnightly follow ups. Data of all patients was recorded on Performa and was entered and analyzed for descriptive statistics in PASW 18 (IBM®. SPSS). Results: A total of 164 subjects were included in the study who were subdivided into three groups labeled as A, B and C for laser therapy treatment, amitryptaline treatment and controls respectively. The mean age of subjects was 51.54+/-10.46 in Group A, 49.38+/-10.56 in Group B and 51.70+/-11.43 in Group C. The difference of mean ages in all study groups was statistically insignificant (p-value= 0.469). The average pain score in patients who received laser therapy was 5.95+/-0.91 before treatment, whereas after treatment it was 4.31+/-0.98. The mean pain score in subjects having Amitryptaline before starting the treatment was 6.87+/-0.71 and after treatment, it was 6.23+/-0.98. The mean score for daily life activities in subjects who received laser therapy was 9.562.37 before treatment, while after treatment it was 7.56+/-1.54. The average score
Romero-Sandoval, E Alfonso; Asbill, Scott; Paige, Candler A; Byrd-Glover, Kiara
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.
Sanna, Maria Domenica; Lucarini, Laura; Durante, Mariaconcetta; Ghelardini, Carla; Masini, Emanuela; Galeotti, Nicoletta
Neuropathic pain is under-treated, with a detrimental effect on quality of life, partly because of low treatment efficacy, but also because pathophysiological mechanisms are not fully elucidated. To clarify the pathobiology of neuropathic pain, we studied the contribution of neuroinflammation and oxidative stress in a model of peripheral neuropathy. We also assessed an innovative treatment for neuropathic pain by investigating the effects of histamine H4 receptor ligands in this model. A peripheral mononeuropathy was induced in mice, by spared nerve injury (SNI). Neuroinflammation and oxidative stress parameters were evaluated by spectrophotometry. The mechanical (von Frey test) and thermal (plantar test) nociceptive thresholds were evaluated. SNI mice showed increased expression of the pro-inflammatory cytokines IL-1ß and TNF-α, decreased antioxidant enzyme Mn-containing SOD (MnSOD), increased levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an indicator of oxidative DNA damage, and of PARP, nuclear enzyme activated upon DNA damage. Intrathecal administration of VUF 8430 (H4 receptor agonist) reversed the mechanical and thermal allodynia and was associated with decreased expression of IL-1ß, TNF-α, 8-OHdG and PARP and with restoration of MnSOD activity in the spinal cord and sciatic nerve. These effects were prevented by JNJ 10191584 (H4 receptor antagonist). In the SNI mouse model of neuropathic pain, neuronal H4 receptor stimulation counteracts hyperalgesia and reduces neuroinflammation and oxidative stress in the spinal cord and sciatic nerve. Targeting both oxidative stress and pro-neuroinflammatory pathways through H4 receptor-mediated mechanisms could have promising therapeutic potential for neuropathic pain management. © 2016 The British Pharmacological Society.
Olga A. Klochkova
Full Text Available Autosomal recessive peripheral neuropathy with neuromyotonia (ARAN-NM is a relatively newly described disease associated with mutations in the HINT1 gene. It accounts for a significant part of the poorly differentiated forms of axonal polyneuropathies. We present the first in Russia description of the genetically confirmed case of ARAN-NM in a boy aged 14 years and 11 months without the hereditary-tainted anamnesis. On presentation, the patient experienced progressive distal muscular weakness, asymmetric foot deformity, gait disorders and minimal manifestations of neuromyotonia (stiffness in the fingers. During examination, we detected an increase in the level of creatine phosphokinase up to 635 U/l, a disturbance of conduction of motor and, to a lesser extent, sensory fibers of the peripheral nerves (according to the stimulation electromyography, EMG, denervation-reinnervation changes, single positive acute waves, fibrillation potentials, complex repeated discharge (according to the data of needle EMG. In the study of exome, a homozygous mutation c.110G>C, p.R37P was determined in exon 01 of the HINT1 gene, which confirmed the presence of ARAN-NM. A molecular-genetic examination of the patient's immediate relatives was carried out. The described case is compared with literature data. An overview of currently available information on ARAN-NM is provided. Diagnostic criteria of the disease are presented.
Richardson, James K; Eckner, James T; Allet, Lara; Kim, Hogene; Ashton-Miller, James A
The aim of this work was to identify relationships between complex and simple clinical measures of reaction time (RTclin) and indicators of balance in older subjects with and without diabetic peripheral neuropathy (DPN). Prospective cohort design. Complex RTclin accuracy, simple RTclin latency, and their ratio were determined using a novel device in 42 subjects (mean ± SD age, 69.1 ± 8.3 yrs), 26 with DPN and 16 without. Dependent variables included unipedal stance time (UST), step width variability and range on an uneven surface, and major fall-related injury over 12 months. In the DPN subjects, the ratio of complex RTclin accuracy to simple RTclin latency was strongly associated with longer UST (R/P = 0.653/0.004), and decreased step width variability and range (R/P = -0.696/0.001 and -0.782/injuries had lower complex RTclin accuracy:simple RTclin latency than those without. The ratio of complex RTclin accuracy:simple RTclin latency is a potent predictor of UST and frontal plane gait variability in response to perturbations and may predict major fall injury in older subjects with DPN. These short latency neurocognitive measures may compensate for lower limb neuromuscular impairments and provide a more comprehensive understanding of balance and fall risk.
Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna
Pain-sensing sensory neurons (nociceptors) of the dorsal root ganglion (DRG) can become sensitized (hyperexcitable) in response to pathological conditions such as diabetes, which in turn may lead to the development of painful peripheral diabetic neuropathy (PDN). Because of insufficient knowledge about the mechanisms for this hypersensitization, current treatment for painful PDN has been limited to somewhat nonspecific systemic drugs having significant side effects or potential for abuse. Recent studies have established that the CaV3.2 isoform of T-channels makes a previously unrecognized contribution to sensitization of pain responses by enhancing excitability of nociceptors in animal models of type 1 and type 2 PDN. Furthermore, it has been reported that the glycosylation inhibitor neuraminidase can inhibit the native and recombinant CaV3.2 T-currents in vitro and completely reverse mechanical and thermal hyperalgesia in diabetic animals with PDN in vivo. Understanding details of posttranslational regulation of nociceptive channel activity via glycosylation may facilitate development of novel therapies for treatment of painful PDN. Pharmacological targeting the specific pathogenic mechanism rather than the channel per se may cause fewer side effects and reduce the potential for drug abuse in patients with diabetes.
Watanabe, T; Mitsuhashi, M; Sagawa, M; Ri, M; Suzuki, K; Abe, M; Ohmachi, K; Nakagawa, Y; Nakamura, S; Chosa, M; Iida, S; Kizaki, M
The proteasome inhibitor bortezomib has revolutionized the treatment of multiple myeloma. However, bortezomib-induced peripheral neuropathy (BiPN) is a serious complication that compromises clinical outcome. If patients with a risk of developing BiPN could be predicted, physicians might prefer weekly, reduced-dose, or subcutaneous approaches. To seek biomarkers for BiPN, we conducted a multicenter prospective study using a simple and unique system. Multiple myeloma patients received twice-weekly or weekly 1.3 mg/m(2) bortezomib intravenously, and a 2-ml sample of whole blood was obtained before treatment and 2-3 days and 1-3 weeks after the first dose. Induction of gene expression was then quantified by real-time PCR. Of a total of 64 enrolled patients, 53 patient samples qualified for mRNA analysis. The BiPN grade was associated with phytohemagglutinin-induced IL2, IFNG and TNFSF2, as well as with lipopolysaccharide-induced IL6 levels. More importantly, of the 19 patients showing a 3-fold increase in phytohemagglutinin-induced IL2, 14 did not suffer from BiPN (73.7% prediction), whereas of the 34 patients with a IL2 mRNA levels in whole blood serve as a promising biomarker for predicting BiPN, and this finding warrants validation in a larger study.
Raskin, Philip; Huffman, Cynthia; Yurkewicz, Lorraine; Pauer, Lynne; Scavone, Joseph M; Yang, Ruoyong; Parsons, Bruce
To evaluate pregabalin's efficacy and safety versus placebo to reduce pain in patients with diabetic peripheral neuropathy (DPN) using a concomitant nonsteroidal anti-inflammatory drug. In a randomized, double-masked, 14-week, 2-period, crossover study, patients with painful DPN using a nonsteroidal anti-inflammatory drug for non-DPN-related pain received 150 to 300 mg/d pregabalin or placebo (period 1); 14-day washout; then, the opposite therapy (period 2). Endpoints included weekly change in DPN pain score, sleep interference, adverse events, and patient-reported outcomes. Patients with similar baseline characteristics were randomized (period 1) to 1 of the 2 following possible sequences: pregabalin→placebo (n=154) or placebo→pregabalin (n=147). Results of the primary efficacy measure, mean weekly DPN pain at endpoint, showed no significant difference between pregabalin and placebo. However, 1 sensitivity analysis (mixed-model repeated measures) found greater pain score reductions with pregabalin than placebo at weeks 2 to 4 and overall (all Ppregabalin over placebo (P=0.0009). Other sensitivity and secondary analyses were nonsignificant. Treatment-emergent adverse events were consistent with the known safety profile of pregabalin. Pregabalin (vs. placebo) showed overall improvements in sleep, pain reduction in 1 sensitivity analysis, and was well tolerated. Potential factors that may have confounded the ability to detect a treatment difference in DPN pain reduction (high placebo response, carryover effect, short washout period, or pregabalin dose) are discussed in the context of future studies.
Koh, Youngil; Lee, So Young; Kim, Inho; Kwon, Ji-Hyun; Yoon, Sung-Soo; Park, Seonyang; Chung, Mi Hye; Suh, Sung Yun; Kim, Kwi Suk; Kim, Hyang Sook
Bortezomib-induced peripheral neuropathy (BIPN) is a significant neurotoxicity, requiring dose reduction or the delay of treatment. In a multicentre trial including 97 % Caucasians and 3 % Asians, BIPN was shown to occur less frequently in cases in which bortezomib was administered subcutaneously. Considering the different pharmacokinetics between Caucasians and Asians, we analysed BIPN according to the administration route, specifically in Korean myeloma patients. We surveyed the prescribed anticonvulsants for the treatment of BIPN and analysed the data after stratifying the results by the cumulative dose of bortezomib. Exclusion criteria were as follows: treated with administration route during the treatment, or receiving anticonvulsants for other reasons prior to bortezomib administration. A total of 101 patients were enrolled; 60 were treated with bortezomib and dexamethasone, and 37 were treated with bortezomib, melphalan, and prednisolone. The median number of treatment courses was four for each regimens. The median exposure to bortezomib for all patients was 19 mg/m(2). Progression-free survival (PFS) and overall survival rates were not statistically different between the groups. There was no difference in the proportion of patients requiring medical treatment (p = 0.388). After stratifying the results, BIPN developed less frequently when bortezomib was administered subcutaneously rather than intravenously in patients receiving more than 23.4 mg/m(2) of bortezomib (p administration route, the subcutaneous injection of bortezomib should be considered in Asian myeloma patients who are expected to achieve a longer PFS with bortezomib.
McDougall, Jason J; Muley, Milind M; Philpott, Holly T; Reid, Allison; Krustev, Eugene
The endocannabinoid system has been shown to reduce inflammatory flares and pain in rodent models of arthritis. A limitation of endocannabinoids is that they are rapidly denatured by hydrolysing enzymes such as fatty acid amide hydrolase (FAAH) which renders them physiologically inert. Osteoarthritis (OA) is primarily a degenerative joint disease; however, it can incorporate mild inflammation and peripheral neuropathy. The aim of this study was to determine whether early blockade of FAAH bioactivity could reduce OA-associated inflammation and joint neuropathy. The ability of this treatment to prevent end-stage OA pain development was also tested. Physiological saline or sodium monoiodoacetate (MIA; 0.3 mg) was injected into the right knee of male C57Bl/6 mice (20-42 g) and joint inflammation (oedema, blood flow and leukocyte trafficking) was measured over 14 days. Joint inflammation was also measured in a separate cohort of animals treated on day 1 with either saline or the FAAH inhibitor URB597 (0.03-0.3 mg/kg topical onto the knee joint). In other experiments, von Frey hair tactile sensitivity was determined on days 1 and 14 in MIA-injected mice treated prophylactically with URB597 (0.3 mg/kg s.c. over the knee joint on days 0-3). Saphenous nerve myelination was also assessed in these animals on day 14 by G-ratio analysis. Intra-articular injection of MIA caused an increase in joint oedema (P day 1 after treatment which subsequently resolved over later time points. This acute inflammatory response was ameliorated by local URB597 treatment. Prophylactic local administration of URB597 prevented MIA-induced saphenous nerve demyelination, and chronic joint pain was also attenuated. These data indicate that local inhibition of FAAH in MIA-injected knees can reduce acute inflammatory changes associated with the model. Prophylactic treatment of OA mice with the endocannabinoid hydrolysis inhibitor URB597 was also shown to be neuroprotective and prevented the
Full Text Available Hereditary sensory and autonomic neuropathy type 2 (HSNAII is a rare pathology characterized by an early onset of severe sensory loss (all modalities in the distal limbs. It is due to autosomal recessive mutations confined to exon "HSN2" of the WNK1 (with-no-lysine protein kinase 1 serine-threonine kinase. While this kinase is well studied in the kidneys, little is known about its role in the nervous system. We hypothesized that the truncating mutations present in the neural-specific HSN2 exon lead to a loss-of-function of the WNK1 kinase, impairing development of the peripheral sensory system. To investigate the mechanisms by which the loss of WNK1/HSN2 isoform function causes HSANII, we used the embryonic zebrafish model and observed strong expression of WNK1/HSN2 in neuromasts of the peripheral lateral line (PLL system by immunohistochemistry. Knocking down wnk1/hsn2 in embryos using antisense morpholino oligonucleotides led to improper PLL development. We then investigated the reported interaction between the WNK1 kinase and neuronal potassium chloride cotransporter KCC2, as this transporter is a target of WNK1 phosphorylation. In situ hybridization revealed kcc2 expression in mature neuromasts of the PLL and semi-quantitative RT-PCR of wnk1/hsn2 knockdown embryos showed an increased expression of kcc2 mRNA. Furthermore, overexpression of human KCC2 mRNA in embryos replicated the wnk1/hsn2 knockdown phenotype. We validated these results by obtaining double knockdown embryos, both for wnk1/hsn2 and kcc2, which alleviated the PLL defects. Interestingly, overexpression of inactive mutant KCC2-C568A, which does not extrude ions, allowed a phenocopy of the PLL defects. These results suggest a pathway in which WNK1/HSN2 interacts with KCC2, producing a novel regulation of its transcription independent of KCC2's activation, where a loss-of-function mutation in WNK1 induces an overexpression of KCC2 and hinders proper peripheral sensory nerve
Chemotherapy is increasingly being administered as a treatment for cancer and with it are a number of possible side effects. One, which has a negative impact on a patient's quality of life and their self-esteem, is that of chemotherapy-induced alopecia (CIA). A side effect of which, for some, could be prevented by the use of scalp cooling, dependent on the regimen being administered and patient choice. This article explores the issue of CIA from the patient's perspective and scalp cooling as a preventative measure, along with a review of the evidence around the risk associated with developing scalp metastases following scalp cooling. It also discusses why scalp cooling should be available for both male and female patients; along with the potential impact scalp cooling may have on clinical areas delivering chemotherapy.
Carnel, S.B.; Blakeslee, D.B.; Oswald, S.G.; Barnes, M. (Fitzsimons Army Medical Center, Aurora, CO (USA))
Severe stomatitis is a common problem encountered during either radiation therapy or chemotherapy. Most therapeutic regimens are empirical, with no scientific basis. The purpose of this study is to determine the efficacy of various topical solutions in the treatment of radiation- or chemotherapy-induced stomatitis. Eighteen patients were entered into a prospective double-blinded study to test several topical solutions: (1) viscous lidocaine with 1% cocaine; (2) dyclonine hydrochloride 1.0% (Dyclone); (3) kaolin-pectin solution, diphenhydramine plus saline (KBS); and (4) a placebo solution. Degree of pain relief, duration of relief, side effects, and palatability were evaluated. The results showed that Dyclone provided the most pain relief. Dyclone and viscous lidocaine with 1% cocaine provided the longest pain relief, which averaged 50 minutes This study provides objective data and defines useful guidelines for treatment of stomatitis.
The number of children and young people diagnosed with cancer is increasing every year. Pain is a significant side effect of disease, surgery and treatments including chemotherapy. After a course of intensive chemotherapy, some children develop oral mucositis, a debilitating condition causing bleeding, pain and inflammation. Moderate and severe mucositis pain is treated with continued good oral hygiene and parenteral analgesia. The aim of this article is to identify challenges in managing chemotherapy-induced oral mucositis pain in children, and to highlight the benefits of adding ketamine as an adjuvant analgesic. A small number of studies and case reports in children have examined ketamine for cancer pain and have demonstrated its successful use in the treatment of chronic pain conditions. However, there remtains a paucity of data about the efficacy of continuous low dose ketamine administration in children with cancer. Further studies are required to establish its benefits to support the addition of ketamine to the World Health Organization's analgesic ladder.
Matsos, A; Loomes, M; Zhou, I; Macmillan, E; Sabel, I; Rotziokos, E; Beckwith, W; Johnston, I N
Whilst chemotherapeutic agents show promising results in the amelioration of cancerous tumors, patients often experience cognitive disturbances associated with chemotherapy long after treatment has ceased. Research has suggested that the structural integrity of white matter fibres in the brain are susceptible to the harmful effects of chemotherapy. Post-chemotherapy, white matter tracts often display altered morphology with a reduction in glial cells such as oligodendrocytes. Demyelination, gliosis and leukoencephalopathy during or post chemotherapy is associated with changes in processing speed and IQ. Thus, understanding the relationship between chemotherapy, white matter damage and cognition is warranted. This review presents evidence for chemotherapy induced white matter damage highlighting the importance of implementing behavioral and pharmological strategies to prevent or reverse such acute toxicity in the brain. Copyright © 2017 Elsevier Ltd. All rights reserved.
Middleton, Jackson A; Roffers, John A
A 22-year-old man was referred for orthopedic follow-up after an ankle injury. Initial evaluation in urgent care included radiographs with negative findings. After a delayed presentation, a course of functional treatment was recommended. Subsequently, he developed a deep venous thrombosis and pulmonary emboli. He was found to be factor V Leiden deficient and was fully anticoagulated on warfarin. Later reevaluation revealed a steppage gait and foot drop. Electrodiagnostic studies (ie, electromyography and nerve conduction studies) revealed a severe peripheral polyneuropathy. The patient admitted to engaging in high-volume recreational use of nitrous oxide. Neurological evaluation confirmed vitamin B12 deficiency consistent with the toxic effects of nitrous oxide. The patient's condition improved with vitamin B supplementation, bracing, and avoidance of nitrous oxide and similar neurotoxins. He participated in a 3-month physical rehabilitation program, and he displayed partial recovery at most recent follow-up. [Orthopedics. 201x; xx(x):xx-xx.]. Copyright 2017, SLACK Incorporated.
Pachman, Deirdre R; Dockter, Travis; Zekan, Patricia J; Fruth, Briant; Ruddy, Kathryn J; Ta, Lauren E; Lafky, Jacqueline M; Dentchev, Todor; Le-Lindqwister, Nguyet Anh; Sikov, William M; Staff, Nathan; Beutler, Andreas S; Loprinzi, Charles L
Paclitaxel is associated with both an acute pain syndrome (P-APS) and chronic chemotherapy-induced peripheral neuropathy (CIPN). Given that extensive animal data suggest that minocycline may prevent chemotherapy-induced neurotoxicity, the purpose of this pilot study was to investigate the efficacy of minocycline for the prevention of CIPN and the P-APS. Patients with breast cancer were enrolled prior to initiating neoadjuvant or adjuvant weekly paclitaxel for 12 weeks and were randomized to receive minocycline 200 mg on day 1 followed by 100 mg twice daily or a matching placebo. Patients completed (1) an acute pain syndrome questionnaire daily during chemotherapy to measure P-APS and (2) the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment, to measure CIPN. Forty-seven patients were randomized. There were no remarkable differences noted between the minocycline and placebo groups for the overall sensory neuropathy score of the EORTC QLQ-CIPN20 or its individual components, which evaluate tingling, numbness and shooting/burning pain in hands and feet. However, patients taking minocycline had a significant reduction in the daily average pain score attributed to P-APS (p = 0.02). Not only were no increased toxicities reported with minocycline, but there was a significant reduction in fatigue (p = 0.02). Results of this pilot study do not support the use of minocycline to prevent CIPN, but suggest that it may reduce P-APS and decrease fatigue; further study of the impact of this agent on those endpoints may be warranted.
Young, Annie; Arif, Azra
Chemotherapy-induced hair loss is a common and distressing side effect of cancer therapy and is one of the major unmet challenges in cancer management. Scalp cooling can prevent chemotherapy-induced hair loss in some cancer patients with solid tumours receiving certain chemotherapy regimens. Recent evidence indicates that this technique does not increase the risk of scalp metastasis. A reduction in post-chemotherapy infusion duration of scalp cooling and the advancement in cool cap technology may assist clinicians in promoting scalp cooling to cancer patients. This article discusses recent research, scalp cooling guidelines, products available and implications for nurses and their organisations in providing scalp cooling. It also considers recent advancements in identifying genes associated with chemotherapy-induced hair loss and international research collaborations including a registry and a 'chemotherapy-induced hair loss action group'--all striving to improve the patient experience of chemotherapy-induced hair loss.
Ashraf Abdelaal Mohamed Abdelaal
Full Text Available Background: Diabetic peripheral polyneuropathy (DPN is an arousing problem that negatively affects body systems. Pulsed low frequency electromagnetic field (PLFEM and Extracorporeal shock waves (ESW are therapeutic modalities frequently used to treat varieties of pathological conditions. Objective of the study was to evaluate and compare effects of PLFEM and ESW on feet blood flow (maximum skin blood perfusion (SBP-max, minimum skin blood perfusion (SBP-min, and basal mean perfusion changes (BMCP (by Laser Doppler and functional balance (by Berg balance scale "BBS" in patients with DPN. Methods: Seventy patients with DPN were randomly assigned into PLFEM, ESW and control groups. PLFEMgroup received treatment twice weekly while ESW received treatment once weekly, for 12 weeks. Variables were evaluated prestudy (evaluation-1, post-study (evaluation-2 and 4-weeks post-treatment cessation (evaluation-3. Results: At evaluation-2 and 3; SBP-max, SBP-min, BMCP and BBS showed significant increase in both PLFEM and ESWgroups (P 0.5. At evaluation-2; SBPmax, SBP-min, BMCP and BBS mean values and percentages of change were [27.21±4.27(23.27 %, 10.51±2.32(50.004%, 16.15±2.22(24.45 %, 43.18±2.95(33.01 %], [24.74±3.33(10.62 %, 8.69±2.58(21.15 %, 14.48±2.35(11.66 %, 40.13±3.52(23.12 %] and [22.12(-0.05 %, 7.196(-0.1 %, 13.06±2.38(-0.09, 32.76(-0.1 %] for LFPEM, ESW and control groups respectively (P<0.05. Conclusion: While both PLFEM and ESW have significant long-term effects in improving lower extremity blood flow and functional balance in patients with DPN, but still PLFEM is more effective than ESW.
Oladipo, O.; Kennedy, R.; Shiels, A.; McAleer, S.
The radiological features of intracranial haemorrhage are well described in the literature, but atypical appearances can sometimes develop. We report a case of chemotherapy-induced thrombocytopenia resulting in fatal intracranial haemorrhage in a man undergoing autologous peripheral stem cell transplantation. The CT showed an unusual appearance, with separation of blood products and fluid within the haemorrhage leading to a wine-glass-shaped outline in the image. This case draws attention to this uncommon radiological finding and emphasises the risks of allosensitisation following chemotherapy and peripheral stem cell transplantation. PMID:21113351
Full Text Available The radiological features of intracranial haemorrhage are well described in the literature, but atypical appearances can sometimes develop. We report a case of chemotherapy-induced thrombocytopenia resulting in fatal intracranial haemorrhage in a man undergoing autologous peripheral stem cell transplantation. The CT showed an unusual appearance, with separation of blood products and fluid within the haemorrhage leading to a wine-glass-shaped outline in the image. This case draws attention to this uncommon radiological finding and emphasises the risks of allosensitisation following chemotherapy and peripheral stem cell transplantation.
Full Text Available Subcutaneous (SC application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM patients treated using either intravenous (IV or subcutaneous (SC route of administration.During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly - 63% or twice weekly - 27% in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥ 3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN. PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥ 2 was present in 20% vs 18% and PN grade ≥ 3 was present in 6% vs 4%.We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.
Vinik, Aaron I; Shapiro, Douglas Y; Rauschkolb, Christine; Lange, Bernd; Karcher, Keith; Pennett, Deborah; Etropolski, Mila S
This study evaluated the efficacy and tolerability of tapentadol extended release (ER) for the management of chronic pain associated with diabetic peripheral neuropathy (DPN). Adults with moderate to severe DPN pain were titrated to tapentadol ER 100-250 mg bid during a 3-week open-label period; patients with ≥1-point reduction in pain intensity (11-point numerical rating scale) at end of titration were randomized to receive placebo or tapentadol ER (optimal dose from titration) for 12 weeks (double-blind, fixed-dose maintenance phase). The primary end point was mean change in average pain intensity from the start to week 12 (last observation carried forward [LOCF]) of the double-blind maintenance phase. A total of 358 patients completed the titration period; 318 patients (placebo, n = 152; tapentadol ER, n = 166) were randomized and received one or more doses of double-blind study medication. Mean (SD) pain intensity (observed case) was 7.33 (1.30) at the start and 4.16 (2.12) at week 3 of the open-label titration period (mean [SD] change, -3.22 [1.97]). The mean (SD) change in pain intensity (LOCF) from start of double-blind treatment to week 12 was as follows: placebo, 1.30 (2.43); tapentadol ER, 0.28 (2.04; least squares mean difference, -0.95 [95% CI -1.42 to -0.49]; P tapentadol ER group during the double-blind maintenance phase were nausea (21.1%) and vomiting (12.7%). Tapentadol ER (100-250 mg bid) was effective and well tolerated for the management of moderate to severe chronic pain associated with DPN. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Alexander, Joe; Edwards, Roger A; Manca, Luigi; Grugni, Roberto; Bonfanti, Gianluca; Emir, Birol; Whalen, Edward; Watt, Stephen; Parsons, Bruce
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 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.
Full Text Available Context and Objective: In view of the growing burden of type 2 diabetes mellitus (T2DM globally and associated microvascular and macrovascular complications, the study was done to assess the prevalence and risk factors for diabetic neuropathy among T2DM patients attending a tertiary care hospital. Subjects and Methods: T2DM patients' ≥30 years of both gender, presenting to the Medicine Department at a tertiary care hospital were included in the study. Diabetic Neuropathy Symptom (DNS questionnaire to assess symptoms and Diabetic Neuropathy Examination (DNE scoring to assess clinical signs were used. Results: A total of 273 patients were included. The mean age was 57.8 ± 11.5 years. The male to female distribution was 75% (202 and 25% (71, respectively. According to DNS instrument, 41.4% patients scored positive for the presence of neuropathy while only 24.5% had neuropathy according to DNE score. The proportion of males affected by neuropathy was more than females. 43.1% males had a positive DNS score while only 27.2% of them had a positive DNE score. Duration of the disease was positively correlated with neuropathy. Neuropathy was more prevalent among people who had higher systolic and diastolic blood pressure as per DNS and DNE instruments. Conclusions: The present study identified a higher proportion of males to be affected by neuropathy. Hence, more detailed evaluation must be accorded to elderly male diabetic patients with longer duration of the disease. Lifestyle modifications and watchful screening need to be incorporated as part of routine patient health education during follow-up clinic visits.
Seyyed Meisam Ebrahimi
Full Text Available Background : Chemotherapy-induced nausea (CIN in the anticipatory and acute phase is the most common side effect in cancer therapy. The purpose of this study was to investigate the effect of ginger capsules on the alleviation of this problem. Methods : This randomized, double-blind, placebo-controlled clinical trial was performed on 80 women with breast cancer between August till December 2009 in Imam Khomeini Hospital, Tehran, Iran. These patients underwent one-day chemotherapy regime and suffering from chemotherapy-induced nausea. After obtaining written consent, samples were randomly assigned into intervention and control groups. Two groups were matched based on the age and emetic effects of chemotherapy drugs used. The intervention group received ginger capsules (250 mg, orally four times a day (1 gr/d and the same samples from the placebo group received starch capsules (250 mg, orally for three days before to three days after chemotherapy. To measure the effect of capsules a three-part questionnaire was used, so the samples filled every night out these tools. After collecting the information, the gathered data were analyzed by statistical tests like Fisher’s exact, Kruskal-Wallis and Chi-square using version 8 of STATA software. Results : The mean ± SD of age in the intervention and placebo groups were 41.8 ± 8.4 and 45.1 ± 10 years, respectively. Results indicated that the severity and number of nausea in the anticipatory phase were significantly lower in the ginger group compared with placebo group (P=0.0008, P=0.0007, respectively. Also, the intensity (P=0.0001 and number (P=0.0001 of nausea in the acute phase were significantly lower in the ginger group. On the other hand, taking ginger capsules compared with placebo did not result in any major complications. Conclusion: Consuming ginger root powder capsules (1 gr/d from three days before chemotherapy till three days after it in combination with the standard anti-emetic regimen can
In order to elucidate the physiological significance of autonomic neuropathy in juvenile diabetics, cardiovascular, hormonal and metabolic functions have been investigated in three groups of juvenile diabetics: One group had no signs of neuropathy, one group had presumably slight autonomic...... neuropathy (reduced beat-to-beat variation in heart rate during hyperventilation) and one group had clinically severe autonomic neuropathy, defined by presence of orthostatic hypotension. In all three experimental situations we found sympathetic dysfunction causing cardiovascular and/or hormonal...... maladjustments in patients with autonomic neuropathy. Regarding metabolic functions we found normal responses to graded exercise and insulin-induced hypoglycemia in patients with autonomic neuropathy in spite of blunted catecholamine responses, suggesting increased sensitivity of glycogen stores and adipose...
Kasai, Mari; Fukuda, Takeshi; Ichimura, Tomoyuki; Yasui, Tomoyo; Sumi, Toshiyuki
Chemotherapy-induced neutropenia is a common complication in cancer treatment. In this study, we investigated chemotherapy-induced neutropenia that was recently detected in all patients with gynecologic malignancy. Between January 2009 and December 2011, we examined cases of chemotherapy-induced neutropenia reported in our hospital. We analyzed the incidence and clinical features of chemotherapy-induced neutropenia and febrile neutropenia in patients with gynecologic malignancy. During the study period, we administered over 1614 infusions (29 regimens) to 291 patients. The median age of the patients was 60 years (range 24–84 years). Chemotherapy-induced neutropenia occurred in 147 (50.5%) patients over 378 (23.4%) chemotherapy cycles. Febrile neutropenia occurred in 20 (6.9%) patients over 25 (1.5%) cycles. The mean duration of neutropenia and fever was 3.6 days (range 1–12 days) and 3.4 days (range 1–9 days), respectively. The source of fever was unexplained by examination or cultures in 14 (56.0%) cycles. There were two cases of neutropenia-related death. Chemotherapy-induced neutropenia was associated with older age (over 70 years) (Pneutropenia was associated with poor performance status (Pneutropenia nor febrile neutropenia was associated with bone marrow metastases or previous radiotherapy. By identifying risk factors for febrile neutropenia, such as performance status, no previous chemotherapy, disseminated disease, and distant metastatic disease, the safe management of chemotherapy-induced neutropenia may be possible in patients with gynecologic malignancy. PMID:26267078
Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
Fatigue; Malignant Ovarian Mixed Epithelial Tumor; Neuropathy; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Pain; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
Heo, Young-A; Deeks, Emma D
Oral rolapitant (Varubi™; Varuby ® ), a long-acting neurokinin-1 (NK 1 ) receptor antagonist (RA), is indicated in the USA and EU as part of an antiemetic regimen to prevent delayed chemotherapy-induced nausea and vomiting (CINV) in adults receiving highly or moderately emetogenic chemotherapy (HEC or MEC). In randomized, phase III trials, a single oral dose of rolapitant 180 mg was effective in preventing delayed CINV compared with placebo, when each was used in combination with a 5-HT 3 RA plus dexamethasone, in adults receiving their first course of HEC or MEC. The benefits of rolapitant were maintained over multiple cycles of chemotherapy. The tolerability profile of rolapitant is similar to that of placebo and consistent with that of other NK 1 RAs. However, rolapitant differs from other existing NK 1 RAs in that it does not interact with CYP3A4, thereby negating the need for dexamethasone dose adjustments and potentially making rolapitant a more suitable option for patients receiving CYP3A4 substrates. Thus, oral rolapitant is an effective and well tolerated NK 1 RA that expands the treatment options for preventing delayed CINV in adults receiving HEC or MEC.
Nasir, Syed Sameer; Schwartzberg, Lee S
Chemotherapy-induced nausea and vomiting (CINV) remains an important adverse effect of cancer therapy. The goal of CINV prophylaxis is to reduce the morbidity associated with nausea and vomiting, as well as to preserve quality of life, while maintaining the desired chemotherapy regimen. The US Food and Drug Administration has recently approved new therapies for prevention of CINV, including the neurokinin-1 (NK1) receptor antagonist rolapitant and the fixed-dose combination of the second-generation 5-hydroxytryptamine type 3 receptor antagonist palonosetron with the novel NK1 receptor antagonist netupitant. Alternative agents, like the atypical antipsychotic olanzapine, have also expanded the options available for preventing delayed and refractory CINV. Consensus guidelines for prevention of CINV from several organizations are generally consistent with one another and are updated based on expert review of available clinical trial data. This article will address changes in CINV guidelines over the past 5 years and provide updates on recently approved agents and agents that are expected to be approved, based on published phase III trials. It will also explore other factors affecting optimal CINV control, including the role of patient-related risk factors and the role of physician adherence to antiemetic guidelines in reducing the residual risk of CINV.
Kim, Gun Min; Kim, Sanghwa; Park, Hyung Seok; Kim, Jee Ye; Nam, Sanggen; Park, Seho; Kim, Seung Il; Kim, DoYoung; Sohn, Joohyuk
The purpose of this work is to determine the prevalence of chemotherapy-induced irreversible alopecia (CIIA), which is defined as an alopecia that exists at least 6 months after completion of chemotherapy and factors affecting CIIA in early breast cancer patients. We performed a cross-sectional study. We retrospectively identified breast cancer patients who had received AC (Adriamycin, Cyclophosphamide) or AC-T (AC followed by Taxane) as neoadjuvant or adjuvant chemotherapy. We conducted questionnaire survey regarding alopecia and measured hair density using phototrichogram. From February 2015 to May 2015, among 265 patients who responded properly to the questionnaire, the women who answered they had severe alopecia (alopecia > 50% of scalp) were 19 patients (7.2%). AC-only and AC-T treated patients reported severe alopecia in 2.7% and 10.5%, respectively, which were significantly different (p < 0.001). Mean hair density was 75 hair/cm 2 (range 42-112) and 75.2/cm 2 (range 48.3-102) on occipital area and vertex area, respectively. Hair loss was the most frequent in parietal area (42.6%). Half of total patients (46%) and 73% of CIIA patients regarded that their hair became thinner after chemotherapy CONCLUSIONS: We found that significant proportion of early breast cancer patients were suffering from severe CIIA, especially when they had been treated with AC followed by taxane regimen.
Ranchoux, Benoît; Günther, Sven; Quarck, Rozenn; Chaumais, Marie-Camille; Dorfmüller, Peter; Antigny, Fabrice; Dumas, Sébastien J; Raymond, Nicolas; Lau, Edmund; Savale, Laurent; Jaïs, Xavier; Sitbon, Olivier; Simonneau, Gérald; Stenmark, Kurt; Cohen-Kaminsky, Sylvia; Humbert, Marc; Montani, David; Perros, Frédéric
Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Kiernan, Jason M; Conradi Stark, Jody; Vallerand, April H
Despite three decades of studies examining music interventions as a mitigant of chemotherapy-induced nausea and vomiting (CINV), to date, no systematic review of this literature exists. . PubMed, Scopus, PsycInfo®, CINAHL®, Cochrane Library, and Google Scholar were searched. Keywords for all databases were music, chemotherapy, and nausea. . All studies were appraised for methodology and results. . 10 studies met inclusion criteria for review. Sample sizes were generally small and nonrandomized. Locus of control for music selection was more often with the investigator rather than the participant. Few studies controlled for the emetogenicity of the chemotherapy administered, nor for known patient-specific risk factors for CINV. . The existing data have been largely generated by nurse scientists, and implications for nursing practice are many, because music interventions are low-cost, easily accessible, and without known adverse effects. However, this specific body of knowledge requires additional substantive inquiry to generate clinically relevant data.
Isabel de Camargo Neves Sacco
statistically different for the proportion of flat feet in AI (p=0,0080 and CSI (p=0,0000 and high feet in Â (p=0,0036. There were significant differences when compared GC and GD in the three indexes: IA (p=0,0027, CSI (p=0,0064, Â (p=0,0296. CONCLUSION: Data showed motor and orthopedic changes originated by peripheral neuropathy, which is responsible for foot changes, causing longitudinal arch crumbling. It was seen that A Angle strongly disagreed when compared with the arch classification made by the other two indexes and therefore, its application needs care.
Randomized Trial of the Effect of Mindfulness-Based Stress Reduction on Pain-Related Disability, Pain Intensity, Health-Related Quality of Life, and A1C in Patients With Painful Diabetic Peripheral Neuropathy.
Nathan, Howard J; Poulin, Patricia; Wozny, Denise; Taljaard, Monica; Smyth, Cathy; Gilron, Ian; Sorisky, Alexander; Lochnan, Heather; Shergill, Yaad
IN BRIEF Painful diabetic peripheral neuropathy (PDPN) has a large negative impact on patients' physical and mental functioning, and pharmacological therapies rarely provide more than partial relief. Mindfulness-based stress reduction (MBSR) is a group psychosocial intervention that was developed for patients with chronic illness who were not responding to existing medical treatments. This study tested the effects of community-based MBSR courses for patients with PDPN. Among patients whose PDPN pharmacotherapy had been optimized in a chronic pain clinic, those randomly assigned to treatment with MBSR experienced improved function, better health-related quality of life, and reduced pain intensity, pain catastrophizing, and depression compared to those receiving usual care.
Russell, James W.; Zilliox, Lindsay A.
Purpose of Review: This article provides an overview for understanding the diagnosis, pathogenesis, and management of diabetic neuropathy. Recent Findings: New information about the pathogenesis of diabetic neuropathy continues to emerge, which will lead to identifying new drug targets. It is clear that the natural history of diabetic neuropathy is changing and the rate of progression is slowing. This is likely because of a combination of earlier diagnosis, improved glycemic management, and improved control of related complications such as hyperlipidemia and hypertension. Early diagnosis is critical, and small fiber neuropathy or subclinical diabetic neuropathy may be reversed or significantly improved with appropriate intervention. The American Academy of Neurology recently published guidelines for the treatment of painful diabetic neuropathy. Summary: Diabetic neuropathy is common and can present with varied clinical presentations discussed in this article. Although treatment currently focuses on pain management, attention should be paid to potential risk factors for neuropathy. For example, glycemic control, hyperlipidemia, and hypertension should be managed with diet, exercise, and medications. Class I or II clinical studies indicate that pregabalin, duloxetine, amitriptyline, gabapentin, and opioids are effective in the management of diabetic neuropathic pain. PMID:25299279
... the appearance of an inverted champagne glass) or scoliosis (curvature of the spine). The symptoms of hereditary neuropathies may be apparent ... the appearance of an inverted champagne glass) or scoliosis (curvature of the spine). The symptoms of hereditary neuropathies may be apparent ...
Full Text Available Abstract Background Offloading plantar pressure is a key strategy for the prevention or healing of neuropathic plantar ulcers in diabetes. Non-removable walking casts, such as total contact casts, are currently considered the gold-standard for offloading this type of wound. However, alternative methods for offloading that are more cost effective and easier to use are continually being sought. The aim of this study was to evaluate the capacity of the DH Pressure Relief Shoe™ to offload high pressure areas under the neuropathic foot in diabetes. Methods A within-subjects, repeated measures design was used. Sixteen participants with diabetic peripheral neuropathy were recruited and three footwear conditions were evaluated in a randomised order: a canvas shoe (the control, the participants’ own standard shoe, and the DH Pressure Relief Shoe™. The primary outcome was peak plantar pressure, measured using the pedar-X® mobile in-shoe system between the three conditions. Results Data analysis was conducted on 14 out of the 16 participants because two participants could not complete data collection. The mean peak pressure values in kPa (±SD for each condition were: control shoe 315.9 (±140.7, participants’ standard shoe 273.0 (±127.1 and DH Pressure Relief Shoe™ 155.4 (±89.9. There was a statistically significant difference in peak plantar pressure between the DH Pressure Relief Shoe™ compared to both the control shoe (p = 0.002 and participants’ standard shoe (p = 0.001. The DH Pressure Relief Shoe™ decreased plantar pressures by 51% compared to the control shoe and by 43% compared to participants’ standard shoe. Importantly, for a couple of study participants, the DH Pressure Relief Shoe™ appeared unsuitable for day-to-day wearing. Conclusions The DH Pressure Relief Shoe™ reduced plantar pressures more than the other two shoe conditions. The DH Pressure Relief Shoe™ may be a useful alternative to current offloading
Alexander, Joe; Edwards, Roger A; Savoldelli, Alberto; Manca, Luigi; Grugni, Roberto; Emir, Birol; Whalen, Ed; Watt, Stephen; Brodsky, Marina; Parsons, Bruce
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
Full Text Available Abstract Background 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. Methods 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. Results 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
Oppenheim, U; Kohen-Raz, R; Alex, D; Kohen-Raz, A; Azarya, M
To explore the posturographic correlates of diabetic neuropathy by comparing the performances of three groups of diabetic patients (severe, moderate, and absent neuropathy) with those of normal subjects and four clinical control groups. Using the Interactive Balance System (Tetrax, Ramat Gan, Israel), based on the assessment of the interaction of vertical pressure fluctuations on four independent platforms, one for each heel and toe part, respectively, posturographic examinations were given to 28 diabetic patients (8 with severe, 12 with moderate, and 8 with no peripheral neuropathy), 30 normal control subjects, and a clinical control group of 52 patients (14 with stage II Parkinson's disease, 13 with brain damage, 7 with whiplash, and 19 with peripheral vestibular pathology). The following posturographic parameters were evaluated; 1) general stability; 2) Fourier analysis showing patterns of sway intensity within eight frequency bands between 0.1 and 3 Hz; 3) weight distribution; 4) synchronization of sway; and 5) performance patterns for eight positions, requiring closure of eyes and standing on an elastic surface, as well as left, right, back, and downward head turns. For positions with closed eyes, diabetic patients with severe and moderate neuropathy were significantly less stable than normal subjects and diabetic patients without neuropathy, but diabetic patients with severe and moderate neuropathy turned out to be as equally unstable as clinical control subjects. However, for sway intensity within the band of 0.5 to 1.00 Hz on positions with lateral head turn with occluded vision, neuropathic diabetic patients performed significantly worse than did both normal and clinical control subjects. The same posturographic parameter also differed significantly between normal subjects and diabetic patients without neuropathy. As reported in previous studies, general instability in diabetic neuropathy is not a sufficiently characteristic correlate of the syndrome. On
Navari, Rudolph M
Chemotherapy-induced nausea and vomiting is a significant clinical issue which affects patient's quality of life and treatment decisions. Significant improvements in the control of chemotherapy-induced nausea and vomiting have occurred in the past 15 years with the introduction of new antiemetic agents 5-HT3, receptor antagonists, neurokinin-1 (NK-1) receptor antagonists, and olanzapine. Aprepitant was the first NK-1 receptor antagonist introduced (2003) for the prevention of chemotherapy-induced nausea and vomiting in combination with a 5-HT3 receptor antagonist and dexamethasone. A second NK-1 receptor antagonist netupitant was approved for use in October 2014. Phase III clinical trials of an additional NK-1 receptor antagonist rolapitant have been completed, and the data have been submitted for regulatory approval. A description of rolapitant and its role in chemotherapy-induced nausea and vomiting will be presented, along with a comparison of the other neurolinin-1 receptor antagonists aprepitant and netupitant.
Jansman, FGA; Sleijfer, DT; de Graaf, JC; Coenen, JLLM; Brouwers, JRBJ
The anticancer agents fluorouracil, raltitrexed, irinotecan and oxaliplatin show limited efficacy in the treatment of colorectal cancer and may be associated with substantial toxicity. Therefore, the prevention and reduction of chemotherapy-induced adverse effects is of major significance, in
Rosendahl, Mikkel; Andersen, Claus Yding; la Cour Freiesleben, Nina
To study ovarian follicular dynamics during chemotherapy to understand the mechanisms behind chemotherapy-induced ovarian follicular depletion and to evaluate whether pretreatment levels of ovarian reserve markers were predictive of the posttreatment levels....
Gilhuis, H.J.; Schelhaas, H.J.; Cruysberg, J.R.M.; Zwarts, M.J.
We report a patient with Leber hereditary optic neuropathy (G11778A mtDNA) and a severe demyelinating neuropathy, for which no other cause except his mitochondrial disorder could be found. The involvement of the peripheral nervous system of patients with LHON, in particular with a 11778 mtDNA, is
Mehdi Sadeghi Shermeh
Full Text Available Background and Aim: Nausea and vomiting are the most common side effects of chemotherapy. The aim of the current study was to assess the effect of ice massage applied to the pericardium 6 (P6 or Neigaun acupuncture point on nausea– vomiting due to chemotherapy in cancer patient. Materials and Methods: In a randomized clinical trial one- blind, 114 patients were randomly divided into three groups. Ice massage group were massaged gently on the skin around P6 point of the hand with ice cube into a wet gauze pad for 7 minutes twice a day with 12-hours interval for 24 hours by the patient. Placebo group were massaged with wooden cube and the control group received no interventions. Nausea and vomiting in three groups rated by Morrow Assessment of Nausea and Emesis (MANE Questionnaire in 4 periods of time in 24 hours was used for the assessment of nausea and vomiting. Results: There were significant decreases in the frequency of nausea (P<0.01 and vomiting (P<0.03 and a decrease in the intensity of nausea (P=0.63 and vomiting (P=0.34 in the case group. Frequency of nausea was significantly lower among placebo group than the control group (P<0.02. Conclusion: Ice massage on Neigaun point is effective on reducing the frequency of chemotherapy induced nausea and vomiting in cancer patients. Placebos, patient-practitioner relationship, suggestion, and the patient's view on nausea and vomiting and the role of interaction between the therapist and the patient is effective to some extent.
Shen, Shiqian; Lim, Grewo; You, Zerong; Ding, Weihua; Huang, Peigen; Ran, Chongzhao; Doheny, Jason; Caravan, Peter; Tate, Samuel; Hu, Kun; Kim, Hyangin; McCabe, Michael; Huang, Bo; Xie, Zhongcong; Kwon, Douglas; Chen, Lucy; Mao, Jianren
Chemotherapy-induced pain is a dose-limiting condition that affects 30% of patients undergoing chemotherapy. We found that gut microbiota promotes the development of chemotherapy-induced mechanical hyperalgesia. Oxaliplatin-induced mechanical hyperalgesia was reduced in germ-free mice and in mice pretreated with antibiotics. Restoring the microbiota of germ-free mice abrogated this protection. These effects appear to be mediated, in part, by TLR4 expressed on hematopoietic cells, including macrophages.
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Amelioration of behavioural, biochemical, and neurophysiological deficits by combination of monosodium glutamate with resveratrol/alpha-lipoic acid/coenzyme Q10 in rat model of cisplatin-induced peripheral neuropathy.
Bhadri, Naini; Sanji, Tejaswi; Madakasira Guggilla, Hariprasad; Razdan, Rema
Cisplatin or cis-diamminedichloroplatinum (II) (CDDP) is a cytotoxic chemotherapeutic agent with dose-dependent peripheral neuropathy as a foremost side effect characterised by ataxia, pain, and sensory impairment. Cumulative drug therapy of CDDP is known to produce severe oxidative damage. It mainly targets and accumulates in dorsal root ganglia that in turn cause damage resulting in secondary nerve fibre axonopathy. In the present study, we investigated the neuroprotective effect of the combination of monosodium glutamate (MSG) with three individual antioxidants, that is, resveratrol, alpha-lipoic acid (ALA), and coenzyme Q10 (CoQ10), in cisplatin (2 mg/kg i.p. twice weekly) induced peripheral neuropathy in rats. After 8 weeks of treatment the degree of neuroprotection was determined by measuring behavioral and electrophysiological properties and sciatic nerve lipid peroxidation, as well as glutathione and catalase levels. The results suggested that pretreatment with the combination of MSG (500 mg/kg/day po) with resveratrol (10 mg/kg/day i.p.) or ALA (20 mg/kg/day i.p.) or CoQ10 (10 mg/kg weekly thrice i.p.) exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol.
Amelioration of Behavioural, Biochemical, and Neurophysiological Deficits by Combination of Monosodium Glutamate with Resveratrol/Alpha-Lipoic Acid/Coenzyme Q10 in Rat Model of Cisplatin-Induced Peripheral Neuropathy
Full Text Available Cisplatin or cis-diamminedichloroplatinum (II (CDDP is a cytotoxic chemotherapeutic agent with dose-dependent peripheral neuropathy as a foremost side effect characterised by ataxia, pain, and sensory impairment. Cumulative drug therapy of CDDP is known to produce severe oxidative damage. It mainly targets and accumulates in dorsal root ganglia that in turn cause damage resulting in secondary nerve fibre axonopathy. In the present study, we investigated the neuroprotective effect of the combination of monosodium glutamate (MSG with three individual antioxidants, that is, resveratrol, alpha-lipoic acid (ALA, and coenzyme Q10 (CoQ10, in cisplatin (2 mg/kg i.p. twice weekly induced peripheral neuropathy in rats. After 8 weeks of treatment the degree of neuroprotection was determined by measuring behavioral and electrophysiological properties and sciatic nerve lipid peroxidation, as well as glutathione and catalase levels. The results suggested that pretreatment with the combination of MSG (500 mg/kg/day po with resveratrol (10 mg/kg/day i.p. or ALA (20 mg/kg/day i.p. or CoQ10 (10 mg/kg weekly thrice i.p. exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol.
Omlin, Aurelius; Sartor, Oliver; Rothermundt, Christian; Cathomas, Richard; De Bono, Johann S; Shen, Liji; Su, Zhen; Gillessen, Silke
We hypothesized that the adverse event (AE) profile of cabazitaxel with regard to alopecia, nail changes, neuropathy, and dysgeusia differs from docetaxel. Prospectively collected data on treatment-emergent AEs (frequency and grade [G]) from clinical trial databases of docetaxel every 3 weeks (q3w) (in TAX327 and VENICE) and cabazitaxel q3w (in TROPIC) were analyzed. The frequency of new or worsening AEs (all G and G3-4) for 1301 patients was significantly less for alopecia, nail changes, neuropathy, and dysgeusia for cabazitaxel compared with docetaxel. Treatment with cabazitaxel might cause less alopecia, nail changes, neuropathy, and dysgeusia compared with docetaxel. Copyright © 2015 Elsevier Inc. All rights reserved.
Thawani, Sujata P; Tanji, Kurenai; De Sousa, Eduardo A; Weimer, Louis H; Brannagan, Thomas H
Bortezomib is a proteasome inhibitor that is frequently used for multiple myeloma and lymphoma. A sensory predominant axonal neuropathy is associated with bortezomib treatment but a demyelinating neuropathy is also described primarily based on electrodiagnostic findings. We report a series of patients treated with bortezomib who developed peripheral neuropathy and were found to have demyelinating features on electrodiagnostic testing. Four patients who developed a bortezomib-induced peripheral neuropathy underwent electrophysiological testing, and 1 patient had a nerve biopsy. The four patients with bortezomib-induced peripheral neuropathy had demyelinating features on their electrophysiological testing. The nerve biopsy performed in 1 patient demonstrated a demyelinating component in a background of axonal degeneration. Although most toxic neuropathies are symmetrical axonal neuropathies, bortezomib is part of a small list of agents that may cause a demyelinating polyneuropathy and axonal degeneration. These findings have been confirmed by nerve biopsy.
Jønsson, V; Schrøder, H D; Nolsøe, C
In eight of 10 consecutive cases of IgM monoclonal gammopathy of undetermined significance (MGUS), the M-protein had specificity towards various tissues as estimated by direct and indirect immunofluorescence studies of skin and/or sural nerve biopsies. Five of the cases had neuropathy. In three o...
Altaf, Rahim; Lund Brixen, Annette; Kristensen, Bent
BACKGROUND: The CAPOX regimen is used for adjuvant treatment of colorectal cancer. A well-known side effect of oxaliplatin, which often leads to dose modification (DM), is acute neuropathy (AN). AN is provoked by cold, and it could therefore be expected that the degree of AN and thereby DM is mor...
Chemotherapeutic Agent Toxicity; Neuropathy; Neurotoxicity Syndrome; Pain; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer
Tsuji, Daiki; Ikeda, Midori; Yamamoto, Keisuke; Nakamori, Harumi; Kim, Yong-Il; Kawasaki, Yohei; Otake, Aki; Yokoi, Mari; Inoue, Kazuyuki; Hirai, Keita; Nakamichi, Hidenori; Tokou, Umi; Shiokawa, Mitsuru; Itoh, Kunihiko
Abstract Chemotherapy-induced neutropenia (CIN) is one of the major adverse events that necessitate chemotherapy dose reduction. This study aimed to evaluate the association between grade 4 neutropenia and genetic polymorphisms in breast cancer patients. In this genetic polymorphism association study, peripheral blood samples from 100 consecutive breast cancer outpatients, between August 2012 and September 2014, treated with doxorubicin and cyclophosphamide (AC) combination chemotherapy were genotyped for polymorphisms in adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), cytochrome P450 (CYP) enzyme-coding genes (CYP2B6 and CYP3A5), glutathione S-transferase (GST), and excision repair cross-complementing 1 (ERCC1). Associations between grade 4 neutropenia and genotypes as well as risk factors were examined using multivariate logistic regression. From 100 patients, 32.0% had grade 4 neutropenia. Multivariate logistic regression analysis revealed that ERCC1 118C > T (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.22–9.69; P = 0.020), CYP2B6∗6 (OR, 4.51; 95% CI, 1.21–16.95; P = 0.025), body mass index (BMI) (OR, 6.94; 95% CI, 1.15–41.67; P = 0.035), and baseline white blood cell (WBC) count (OR, 2.99; 95% CI, 1.06–8.40; P = 0.038) were significant predictors of grade 4 neutropenia. ERCC1 and CYP2B6 gene polymorphisms were associated with the extent of grade 4 neutropenia in patients receiving AC chemotherapy. In addition to previously known risk factors, BMI and WBC counts, ERCC1 and CYP2B6 gene polymorphisms were also identified as independent strong predictors of grade 4 neutropenia. PMID:27858847
Laleh Abadi, MS (PT
Full Text Available Background: Patients with diabetes and peripheral neuropathy demonstrate significantly reduced peak torques at the peripheral joints. Objectives: The aim of this study was to assess isometric and concentric peak torques of the hip joint in people with type II diabetes with and without peripheral neuropathy in comparison with healthy participants. Methods: 27 patients with type II diabetes including 15 patients without peripheral neuropathy, 12 patients with diabetes and peripheral neuropathy and 15 healthy people participated. Isometric and concentric peak torques of hip flexion, extension, adduction and abduction of the non-dominant leg were measured by motorized dynamometer. Results: Peak and average peak concentric torques of the hip extension and abduction in patients with diabetes and peripheral neuropathy were lower than those patients with diabetes and control group. Angle of extension peak torque was significantly greater in patients with diabetes and peripheral neuropathy compared with other groups. Angle of flexion peak torque was lower in the patients with diabetes and peripheral neuropathy. Conclusions: Torque related parameters in patients with type II diabetes with or without peripheral neuropathy, are different from healthy subjects. As a result, patients with diabetes especially with peripheral neuropathy are more susceptible of injury and disability in lower limbs. Keywords: type II diabetes, hip, joint, torques, peripheral neuropathy
Tsuboi, Kentaro; Mizukami, Hiroki; Inaba, Wataru; Baba, Masayuki; Yagihashi, Soroku
Incretin-related therapy was found to be beneficial for experimental diabetic neuropathy, but its mechanism is obscure. The purpose of this study is to explore the mechanism through which dipeptidyl peptidase IV inhibitor, vildagliptin (VG), influences neuropathy in diabetic rodents. To this end, non-obese type 2 diabetic Goto-Kakizaki rats (GK) and streptozotocin (STZ)-induced diabetic mice were treated with VG orally. Neuropathy was evaluated by nerve conduction velocity (NCV) in both GK and STZ-diabetic mice, whereas calcitonin-gene-related peptide (CGRP) expressions, neuronal cell size of dorsal root ganglion (DRG) and intraepidermal nerve fiber density (IENFD) were examined in GK. DRG from GK and STZ-diabetic mice served for analyses of GLP-1 and insulin signaling. As results, VG-treatment improved glucose intolerance and increased serum insulin and GLP-1 in GK accompanied by the amelioration of delayed NCV and neuronal atrophy, reduced CGRP expressions and IENFD. Diet restriction alone did not significantly influence these measures. Impaired GLP-1 signals such as CREB, PKB/Akt and S6RP in DRG of GK were restored in VG-treated group, but the effect was equivocal in diet-treated GK. Concurrently, decreased phosphorylation of insulin receptor substrate-2 (IRS2) in GK was corrected by VG-treatment. Consistent with the effect on GK, VG-treatment improved NCV in diabetic mice without influence on hyperglycemia. DRG of VG-treated diabetic mice were characterized by correction of GLP-1 signals and IRS2 phosphorylation without effects on insulin receptor-β expression. The results suggest close association of neuropathy development with impaired signaling of insulin and GLP-1 in diabetic rodents. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Full Text Available Accumulating evidence suggests that Japanese herbal medicines, called Kampo, have beneficial effects on cancer chemotherapy-induced side effects. Rikkunshito ameliorates cisplatin-induced anorexia through an antagonistic effect on the 5-HT receptors and by increasing the serum ghrelin levels. Hangeshashinto improves irinotecan-induced diarrhea and chemotherapy-induced mucositis by inhibiting the activity of β-glucuronidase as well as the synthesis of prostaglandin E2. Goshajinkigan prevents oxaliplatin-induced neurotoxicity, possibly through suppressing functional alterations of the transient receptor potential (TRP channels. In this review, we will summarize the currently available literature regarding the clinical efficacy and potential mechanisms of Kampo medicines in the treatment of cancer chemotherapy-induced side effects.
Shinde, Shivani S; Seisler, Drew; Soori, Gamini; Atherton, Pamela J; Pachman, Deirdre R; Lafky, Jacqueline; Ruddy, Kathryn J; Loprinzi, Charles L
Paclitaxel can cause an acute pain syndrome (P-APS), considered to be an acute form of neuropathy and chronic chemotherapy-induced peripheral neuropathy (CIPN). Anecdotal reports suggested that gabapentin may be helpful in the prevention of these toxicities. The purpose of this pilot study was to obtain data to support or refute the utility of pregabalin for the prevention of P-APS and CIPN. Patients scheduled to receive weekly paclitaxel (80 mg/m(2)/dose) were randomized 1:1 to receive pregabalin 75 mg or a placebo, twice daily, during the 12 weeks of chemotherapy. Patients completed the European Organization of Research and Treatment of Cancer Quality of Life (EORTC QLQ) CIPN20 questionnaire at baseline, prior to each dose of paclitaxel and monthly for 6 months post-treatment. Patients completed a post-paclitaxel questionnaire for 6 days after each dose of paclitaxel and an acute pain syndrome symptom questionnaire on day 8. The primary end point was to determine the effect of pregabalin on the maximum of the worst acute pain scores for the week following paclitaxel administration for cycle 1. Forty-six patients were randomly assigned to the treatment or placebo arm. There was no suggestion of a difference between the two study arms with regard to P-APS measures. While there was a suggestion that pregabalin decreased numbness, there was no suggestion that it decreased tingling, pain, or the EORTC QLQ-CIPN20 subscale scores. There were no evident toxicity differences between the two study arms. The results of this pilot trial do not support that pregabalin is helpful for preventing P-APS or paclitaxel-associated CIPN.
... home. Accessed April 30, 2015. Tesfaye S. Neuropathy in diabetes. Medicine. 2015;43:26. Accessed May 13, 2015. Coon E (expert opinion). Mayo Clinic, Rochester, Minn. May 14, 2015. June 06, 2015 Original article: http://www.mayoclinic.org/diseases-conditions/autonomic- ...
The diagnosis of autonomic neuropathy is often difficult to establish, since clinical symptoms generally appear late in the course of the disease, and may be non-specific. A number of recently developed quantifiable and reproducible autonomic nerve function tests are reviewed, with emphasis on th...
Obradovic, Aleksandar Lj; Hwang, Sung Mi; Scarpa, Joseph; Hong, Sung Jun; Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna
We recently showed that streptozotocin (STZ) injections in rats lead to the development of painful peripheral diabetic neuropathy (PDN) accompanied by enhancement of CaV3.2 T-type calcium currents (T-currents) and hyperexcitability in dorsal root ganglion (DRG) neurons. Here we used the classical peripherally acting T-channel blocker mibefradil to examine the role of CaV3.2 T-channels as pharmacological targets for treatment of painful PDN. When administered intraperitoneally (i.p.), at clinically relevant doses, mibefradil effectively alleviated heat, cold and mechanical hypersensitivities in STZ-treated diabetic rats in a dose-dependent manner. We also found that CaV3.2 antisense (AS)-treated diabetic rats exhibit a significant decrease in painful PDN compared with mismatch antisense (MIS)-treated diabetic rats. Co-treatment with mibefradil (9 mg/kg i.p.) resulted in reversal of heat, cold and mechanical hypersensitivity in MIS-treated but not in AS-treated diabetic rats, suggesting that mibefradil and CaV3.2 AS share the same cellular target. Using patch-clamp recordings from acutely dissociated DRG neurons, we demonstrated that mibefradil similarly blocked T-currents in diabetic and healthy rats in a voltage-dependent manner by stabilizing inactive states of T-channels. We conclude that antihyperalgesic and antiallodynic effects of mibefradil in PDN are at least partly mediated by inhibition of CaV3.2 channels in peripheral nociceptors. Hence, peripherally acting voltage-dependent T-channel blockers could be very useful in the treatment of painful symptoms of PDN.
Botchkarev, Vladimir A; Sharov, Andrey A
Chemotherapy-induced hair loss is one of the most devastating side effects of cancer treatment. To study the effects of chemotherapeutic agents on the hair follicle, a number of experimental models have been proposed. Yoon et al. report that transplantation of human scalp hair follicles onto chemotherapy-treated immunodeficient mice serves as an excellent in vivo model for chemotherapy-induced hair loss. Yoon et al. demonstrate that (i) the response of human hair follicles grafted onto immunodeficient mice to cyclophosphamide resembles the key features of the chemotherapy-induced hair loss seen in patients with cancer and (ii) this human in vivo model for chemotherapy-induced hair loss is closer to clinical reality than to any earlier models. Undoubtedly, this model will serve as a valuable tool for analyses of the mechanisms that underlie this devastating side effect of anti-cancer therapy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Background. Chemotherapy-induced neutropenia (CIN) can result in poor tolerance of chemotherapy, leading to dose reductions, delays in therapy schedules, morbidity and mortality. Actively identifying predisposing risk factors before treatment is of paramount importance. We hypothesised that chemotherapy is associated ...
Davidsen, Marie Louise; Würts, S.Ø.; Rømer, Maria Unni Koefoed
this hypothesis, we have established TIMP-1 gene-deficient and TIMP-1 wild-type fibrosarcoma cells from mouse lung tissue. We have characterised these cells with regard to TIMP-1 genotype, TIMP-1 expression, malignant transformation and sensitivity to chemotherapy-induced apoptosis. We show that TIMP-1 gene...
Schafflick, David; Kieseier, Bernd C; Wiendl, Heinz; Meyer Zu Horste, Gerd
Inflammatory neuropathies are rare autoimmune-mediated disorders affecting the peripheral nervous system. Considerable progress has recently been made in understanding pathomechanisms of these disorders which will be essential for developing novel diagnostic and therapeutic strategies in the future. Here, we summarize our current understanding of antigenic targets and the relevance of new immunological concepts for inflammatory neuropathies. In addition, we provide an overview of available animal models of acute and chronic variants and how new diagnostic tools such as magnetic resonance imaging and novel therapeutic candidates will benefit patients with inflammatory neuropathies in the future. This review thus illustrates the gap between pre-clinical and clinical findings and aims to outline future directions of development.
Callaghan, Brian C.; Cheng, Hsinlin; Stables, Catherine L.; Smith, Andrea L.; Feldman, Eva L.
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
Role of magnetic resonance imaging in entrapment and compressive neuropathy - what, where, and how to see the peripheral nerves on the musculoskeletal magnetic resonance image: Part 2. Upper extremity
Kim, Sungjun [Yonsei University, Department of Diagnostic Radiology, College of Medicine, Seoul (Korea); Hanyang University, Kuri Hospital, Department of Diagnostic Radiology, College of Medicine, Kuri City, Kyunggi-do (Korea); Choi, Jin-Young; Huh, Yong-Min; Song, Ho-Taek; Lee, Sung-Ah [Yonsei University, Department of Diagnostic Radiology, College of Medicine, Seoul (Korea); Kim, Seung Min [Yonsei University, Department of Neurology, College of Medicine, Seoul (Korea); Suh, Jin-Suck [Yonsei University, Department of Diagnostic Radiology, College of Medicine, Seoul (Korea); Yonsei University, Research Institute of Radiological Science, College of Medicine, Seoul (Korea)
The diagnosis of nerve entrapment and compressive neuropathy has been traditionally based on the clinical and electrodiagnostic examinations. As a result of improvements in the magnetic resonance (MR) imaging modality, it plays not only a fundamental role in the detection of space-occupying lesions, but also a compensatory role in clinically and electrodiagnostically inconclusive cases. Although ultrasound has undergone further development in the past decades and shows high resolution capabilities, it has inherent limitations due to its operator dependency. We review the course of normal peripheral nerves, as well as various clinical demonstrations and pathological features of compressed and entrapped nerves in the upper extremities on MR imaging, according to the nerves involved. The common sites of nerve entrapment of the upper extremity are as follows: the brachial plexus of the thoracic outlet; axillary nerve of the quadrilateral space; radial nerve of the radial tunnel; ulnar nerve of the cubital tunnel and Guyon's canal; median nerve of the pronator syndrome, anterior interosseous nerve syndrome, and carpal tunnel syndrome. Although MR imaging can depict the peripheral nerves in the extremities effectively, radiologists should be familiar with nerve pathways, common sites of nerve compression, and common space-occupying lesions resulting in nerve compression in MR imaging. (orig.)
Role of magnetic resonance imaging in entrapment and compressive neuropathy--what, where, and how to see the peripheral nerves on the musculoskeletal magnetic resonance image: part 2. Upper extremity.
Kim, Sungjun; Choi, Jin-Young; Huh, Yong-Min; Song, Ho-Taek; Lee, Sung-Ah; Kim, Seung Min; Suh, Jin-Suck
The diagnosis of nerve entrapment and compressive neuropathy has been traditionally based on the clinical and electrodiagnostic examinations. As a result of improvements in the magnetic resonance (MR) imaging modality, it plays not only a fundamental role in the detection of space-occupying lesions, but also a compensatory role in clinically and electrodiagnostically inconclusive cases. Although ultrasound has undergone further development in the past decades and shows high resolution capabilities, it has inherent limitations due to its operator dependency. We review the course of normal peripheral nerves, as well as various clinical demonstrations and pathological features of compressed and entrapped nerves in the upper extremities on MR imaging, according to the nerves involved. The common sites of nerve entrapment of the upper extremity are as follows: the brachial plexus of the thoracic outlet; axillary nerve of the quadrilateral space; radial nerve of the radial tunnel; ulnar nerve of the cubital tunnel and Guyon's canal; median nerve of the pronator syndrome, anterior interosseous nerve syndrome, and carpal tunnel syndrome. Although MR imaging can depict the peripheral nerves in the extremities effectively, radiologists should be familiar with nerve pathways, common sites of nerve compression, and common space-occupying lesions resulting in nerve compression in MR imaging.
Bour-Jordan, Helene; Thompson, Heather L; Bluestone, Jeffrey A
...) are protected from autoimmune diabetes but develop a spontaneous autoimmune peripheral neuropathy that resembles human diseases Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy...
Sintomas ansiosos e depressivos e sua correlação com intensidade da dor em pacientes com neuropatia periférica Anxious and depressive symptoms and their correlation with pain severity in patients with peripheral neuropathy