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Sample records for peripheral neuropathy symptoms

  1. Peripheral Neuropathy: Symptoms and Signs

    MedlinePlus

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

  2. Peripheral Neuropathy

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Peripheral Neuropathy Information Page Condensed from Peripheral Neuropathy Fact Sheet ... Español Additional resources from MedlinePlus What is Peripheral Neuropathy? Peripheral neuropathy describes damage to the peripheral nervous ...

  3. Peripheral neuropathy

    MedlinePlus

    Peripheral neuritis; Neuropathy - peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy ... Neuropathy is very common. There are many types and causes. Often, no cause can be found. Some ...

  4. Peripheral Neuropathy

    MedlinePlus

    ... can be associated with peripheral neuropathy. Metabolic and endocrine disorders impair the body’s ability to transform nutrients into ... to neuropathies as a result of chemical imbalances. Endocrine disorders that lead to hormonal imbalances can disturb normal ...

  5. Peripheral Neuropathy Caused by Paclitaxel and Docetaxel: An Evaluation and Comparison of Symptoms

    PubMed Central

    Tofthagen*, Cindy; McAllister, R. Denise; Visovsky, Constance

    2013-01-01

    The purpose of this study was to explore the prevalence, severity, distress, and timing of neuropathic symptoms in cancer patients receiving taxanes and to explore neuropathy-related interference with activities. In this descriptive, cross-sectional study, 68 adult outpatients receiving paclitaxel (n = 36) and docetaxel (n = 32) completed the Chemotherapy Induced Peripheral Neuropathy Assessment Tool and a demographic questionnaire. Muscle or joint aches were the most prevalent symptom. Muscle or joint aches were also the most severe and distressing symptom in persons receiving paclitaxel. Participants receiving paclitaxel reported that neuropathic symptoms interfered with a mean of 7.3 (standard deviation [SD] = 4.1) of 14 activities. Nerve pain was the most severe and distressing symptom in persons receiving docetaxel. Participants receiving docetaxel reported that neuropathic symptoms interfered with a mean of 7.1 (SD = 4.1) of 14 activities. Numbness in the feet was the most frequent or constant symptom in persons receiving paclitaxel or docetaxel. Patients receiving paclitaxel and docetaxel experienced similar symptoms of peripheral neuropathy and interference with activities. Continued focus on treatment of painful neuropathy including myalgias and arthralgias is needed. PMID:25032002

  6. [Chemotherapy induced peripheral neuropathy].

    PubMed

    Kolak, Agnieszka; Starosławska, Elzbieta; Kubiatowski, Tomasz; Kieszko, Dariusz; Cisek, Paweł; Patyra, Krzysztof Ireneusz; Surdyka, Dariusz; Mocarska, Agnieszka; Burdan, Franciszek

    2013-11-01

    Modern cancer therapy prolongs patients life but commonly increases incidence of treatment-related complications. One of such adverse effect is a neurotoxicity, which usually manifestates as peripheral neuropathies (CIPN), characterised by various sensory (tingling, numbness, pain), motor (foot and hands drop, fastening buttons difficulties) and autonomic (constipation, arythmia) abnormalities as well as pain. Despite of intensive epidemiological and clinical studies, standardized diagnostic criteria and methods of the neuropathy prevention and treatment have not been fully established. The most commonly used form of treatment is symptomatic therapy, including anticonvulsant and antidepressant drugs. Proper education of patients and their families of symptoms and neuropathy consequences is desirable to reduce anxiety and stress. PMID:24575651

  7. Symptom management and self-care for peripheral neuropathy in HIV/AIDS.

    PubMed

    Nicholas, P K; Kemppainen, J K; Canaval, G E; Corless, I B; Sefcik, E F; Nokes, K M; Bain, C A; Kirksey, K M; Eller, L Sanzero; Dole, P J; Hamilton, M J; Coleman, C L; Holzemer, W L; Reynolds, N R; Portillo, C J; Bunch, E H; Wantland, D J; Voss, J; Phillips, R; Tsai, Y-F; Mendez, M Rivero; Lindgren, T G; Davis, S M; Gallagher, D M

    2007-02-01

    Peripheral neuropathy is the most common neurological complication in HIV and is often associated with antiretroviral therapy. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of peripheral neuropathy in HIV disease, sociodemographic and disease-related correlates and self-care strategies. A convenience sample of 1,217 respondents was recruited from data collection sites in several US cities, Puerto Rico, Colombia and Taiwan. Results of the study indicated that respondents with peripheral neuropathy (n=450) identified 20 self-care behaviors including complementary therapies, use of medications, exercise and rest and/or elevation of extremities. Ratings of frequency and effectiveness were also included. An activities checklist summarized into five categories of self-care behaviors including activities/thoughts, exercise, medications, complementary therapies and substance was used to determine self-care behaviors. Taking a hot bath was the most frequent strategy used by those with peripheral neuropathy (n=292) and received the highest overall rating of effectiveness of any self-management strategies included in this study at 8.1 (scale 1-10). Other self-care strategies to manage this symptom included: staying off the feet (n=258), rubbing the feet with cream (n=177), elevating the feet (n=236), walking (n=262), prescribed anti-epileptic agent (n=80), prescribed analgesics (n=84), over-the-counter medications (n=123), vitamin B (n=122), calcium supplements (n=72), magnesium (n=48), massage (n=156), acupuncture (n=43), reflexology (n=23) and meditation (n=80). Several behaviors that are often deemed unhealthy were included among the strategies reported to alleviate peripheral neuropathy including use of marijuana (n=67), cigarette smoking (n=139), drinking alcohol (n=81) and street drugs (n=30). PMID:17364396

  8. Prevalence, self-care behaviors, and self-care activities for peripheral neuropathy symptoms of HIV/AIDS.

    PubMed

    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

    2010-03-01

    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. PMID:20487335

  9. Painful Peripheral Neuropathies

    PubMed Central

    Marchettini, P; Lacerenza, M; Mauri, E; Marangoni, C

    2006-01-01

    Peripheral neuropathies are a heterogeneous group of diseases affecting peripheral nerves. The causes are multiple: hereditary, metabolic, infectious, inflammatory, toxic, traumatic. The temporal profile includes acute, subacute and chronic conditions. The majority of peripheral neuropathies cause mainly muscle weakness and sensory loss, positive sensory symptoms and sometimes pain. When pain is present, however, it is usually extremely intense and among the most disabling symptoms for the patients. In addition, the neurological origin of the pain is often missed and patients receive inadequate or delayed specific treatment. Independently of the disease causing the peripheral nerve injury, pain originating from axonal pathology or ganglionopathy privileges neuropathies affecting smaller fibres, a clinical observation that points towards abnormal activity within nociceptive afferents as a main generator of pain. Natural activation of blood vessels or perineurial nociceptive network by pathology also causes intense pain. Pain of this kind, i.e. nerve trunk pain, is among the heralding symptoms of inflammatory or ischemic mononeuropathy and for its intensity represents itself a medical emergency. Neuropathic pain quality rekindles the psychophysical experience of peripheral nerves intraneural microstimulation i.e. a combination of large and small fibres sensation temporally distorted compared to physiological perception evoked by natural stimuli. Pins and needles, burning, cramping mixed with numbness, and tingling are the wording most used by patients. Nociceptive pain instead is most often described as aching, deep and dull. Good command of peripheral nerve anatomy and pathophysiology allows timely recognition of the different pain components and targeted treatment, selected according to intensity, type and temporal profile of the pain. PMID:18615140

  10. Peripheral Neuropathy

    MedlinePlus

    ... nerve fibers (myelin). This affects the transmission of pain signals to the brain. PN can be a minor nuisance or a ... can be used. These anti-depressants increase the brain’s transmission of nerve ... symptoms: Narcotic pain relievers such as codeine or methadone can be ...

  11. Propylthiouracil and peripheral neuropathy.

    PubMed

    Van Boekel, V; Godoy, J M; Lamy, L A; Assuf, S; Meyer Neto, J G; Balassiano, S L; Prata, L E

    1992-06-01

    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. PMID:1339201

  12. Peripheral neuropathies 1988

    SciTech Connect

    Assal, J.P.; Liniger, C.

    1990-01-01

    The authors present results and experience in sixteen specific disciplines related to the study of nerve physiopathology, diagnosis and treatment. Twenty-two different peripheral neuropathies are presented, and different models related to health care strategies are discussed. The authors report on Inflammatory and autoimmune neuropathies and Genetic neuropathies.

  13. Inherited Peripheral Neuropathies

    PubMed Central

    Saporta, Mario A.; Shy, Michael E.

    2013-01-01

    SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725

  14. Metabolic correction in the management of diabetic peripheral neuropathy: improving clinical results beyond symptom control.

    PubMed

    Miranda-Massari, J R; Gonzalez, M J; Jimenez, F J; Allende-Vigo, M Z; Duconge, J

    2011-11-01

    Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyl-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metformin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk of

  15. Treatment of peripheral neuropathies.

    PubMed Central

    Hallett, M; Tandon, D; Berardelli, A

    1985-01-01

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

  16. Permanent Peripheral Neuropathy

    PubMed Central

    Higgins, Elizabeth

    2014-01-01

    The health risks and side effects of fluoroquinolone use include the risk of tendon rupture and myasthenia gravis exacerbation, and on August 15, 2013, the Food and Drug Administration updated its warning to include the risk of permanent peripheral neuropathy. We present a case of fluoroquinolone-induced peripheral neuropathy in a patient treated for clinically diagnosed urinary tract infection with ciprofloxacin antibiotic. PMID:26425618

  17. Immunotherapy in Peripheral Neuropathies.

    PubMed

    Léger, Jean-Marc; Guimarães-Costa, Raquel; Muntean, Cristina

    2016-01-01

    Immunotherapy has been investigated in a small subset of peripheral neuropathies, including an acute one, Guillain-Barré syndrome, and 3 chronic forms: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and neuropathy associated with IgM anti-myelin-associated glycoprotein. Several experimental studies and clinical data are strongly suggestive of an immune-mediated pathogenesis. Either cell-mediated mechanisms or antibody responses to Schwann cell, compact myelin, or nodal antigens are considered to act together in an aberrant immune response to cause damage to peripheral nerves. Immunomodulatory treatments used in these neuropathies aim to act at various steps of this pathogenic process. However, there are many phenotypic variants and, consequently, there is a significant difference in the response to immunotherapy between these neuropathies, as well as a need to improve our knowledge and long-term management of chronic forms. PMID:26602549

  18. Diagnostic approach to peripheral neuropathy

    PubMed Central

    Misra, Usha Kant; Kalita, Jayantee; Nair, Pradeep P.

    2008-01-01

    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. PMID:19893645

  19. HIV peripheral neuropathy.

    PubMed

    Gabbai, Alberto Alain; Castelo, Adauto; Oliveira, Acary Souza Bulle

    2013-01-01

    Peripheral neuropathies are the most common neurological manifestations occurring in HIV-infected individuals. Distal symmetrical sensory neuropathy is the most common form encountered today and is one of the few that are specific to HIV infection or its treatment. The wide variety of other neuropathies is akin to the neuropathies seen in the general population and should be managed accordingly. In the pre-ART era, neuropathies were categorized according to the CD4 count and HIV viral load. In the early stages of HIV infection when CD4 count is high, the inflammatory demyelinating neuropathies predominate and in the late stages with the decline of CD4 count opportunistic infection-related neuropathies prevail. That scenario has changed with the present almost universal use of ART (antiretroviral therapy). Hence, HIV-associated peripheral neuropathies are better classified according to their clinical presentations: distal symmetrical polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), mononeuropathies, mononeuropathies multiplex and cranial neuropathies, autonomic neuropathy, lumbosacral polyradiculomyelopathy, and amyotrophic lateral sclerosis (ALS)-like motor neuropathy. Treated with ART, HIV-infected individuals are living longer and are at a higher risk of metabolic and age-related complications; moreover they are also prone to the potentially neurotoxic effects of ART. There are no epidemiological data regarding the incidence and prevalence of the peripheral neuropathies. In the pre-ART era, most data were from case reports, series of patients, and pooled autopsy data. At that time the histopathological evidence of neuropathies in autopsy series was almost 100%. In large prospective cohorts presently being evaluated, it has been found that 57% of HIV-infected individuals have distal symmetrical sensory neuropathy and 38% have neuropathic pain. It is now clear that

  20. Peripheral neuropathies during biologic therapies.

    PubMed

    Yagita, Masato; Hamano, Toshiaki; Hatachi, Saori; Fujita, Masaaki

    2016-01-01

    Peripheral neuropathies should be recognized as the adverse effects of biological agents, especially anti-TNF agents. However, no solid clinical databases for biological agent-associated peripheral neuropathies (BAPN) have been established in Japan. Here we report two cases of peripheral neuropathy associated with anti-TNF agents. One was peroneal motor neuropathy. The other case was chronic inflammatory demyelinating polyradiculoneuropathy. In addition, we summarize the previous reports on BAPN and discuss their prevalence rate, pathogenesis and management. PMID:24313920

  1. Chemotherapy-induced peripheral neuropathy.

    PubMed

    Fehrenbacher, Jill C

    2015-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is common in patients receiving anticancer treatment and can affect survivability and long-term quality of life of the patient following treatment. The symptoms of CIPN primarily include abnormal sensory discrimination of touch, vibration, thermal information, and pain. There is currently a paucity of pharmacological agents to prevent or treat CIPN. The lack of efficacious therapeutics is due, at least in part, to an incomplete understanding of the mechanisms by which chemotherapies alter the sensitivity of sensory neurons. Although the clinical presentation of CIPN can be similar with the various classes of chemotherapeutic agents, there are subtle differences, suggesting that each class of drugs might induce neuropathy via different mechanisms. Multiple mechanisms have been proposed to underlie the development and maintenance of neuropathy; however, most pharmacological agents generated from preclinical experiments have failed to alleviate the symptoms of CIPN in the clinic. Further research is necessary to identify the specific mechanisms by which each class of chemotherapeutics induces neuropathy. PMID:25744683

  2. Autoimmune peripheral neuropathies.

    PubMed

    Bourque, Pierre R; Chardon, Jodi Warman; Massie, Rami

    2015-09-20

    Peripheral nervous system axons and myelin have unique potential protein, proteolipid, and ganglioside antigenic determinants. Despite the existence of a blood-nerve barrier, both humoral and cellular immunity can be directed against peripheral axons and myelin. Molecular mimicry may be triggered at the systemic level, as was best demonstrated in the case of bacterial oligosaccharides. The classification of immune neuropathy has been expanded to take into account specific syndromes that share unique clinical, electrophysiological, prognostic and serological features. Guillain-Barré syndrome encompasses a classical syndrome of acute demyelinating polyradiculoneuropathy and many variants: axonal motor and sensory, axonal motor, Miller-Fisher, autonomic, and sensory. Similarly, chronic immune neuropathy is composed of classic chronic inflammatory demyelinating polyradiculoneuropathy and variants characterized as multifocal (motor or sensorimotor), sensory, distal symmetric, and syndromes associated with monoclonal gammopathy. Among putative biomarkers, myelin associated glycoprotein and several anti-ganglioside autoantibodies have shown statistically significant associations with specific neuropathic syndromes. Currently, the strongest biomarker associations are those linking Miller-Fisher syndrome with anti-GQ1b, multifocal motor neuropathy with anti-GM1, and distal acquired symmetric neuropathy with anti-MAG antibodies. Many other autoantibody associations have been proposed, but presently lack sufficient specificity and sensitivity to qualify as biomarkers. This field of research has contributed to the antigenic characterization of motor and sensory functional systems, as well as helping to define immune neuropathic syndromes with widely different clinical presentation, prognosis and response to therapy. Serologic biomarkers are likely to become even more relevant with the advent of new targeted forms of immunotherapy, such as monoclonal antibodies. PMID:25748038

  3. Vitamin B supplementation for diabetic peripheral neuropathy

    PubMed Central

    Jayabalan, Bhavani; Low, Lian Leng

    2016-01-01

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

  4. Peripheral Neuropathy and Agent Orange

    MedlinePlus

    ... registry health exam . Research on peripheral neuropathy and herbicides The Health and Medicine Division (HMD) (formally known ... acute or subacute onset may be associated with herbicide exposure. Based on this evidence, VA presumed an ...

  5. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep.

    PubMed

    Gore, Mugdha; Brandenburg, Nancy A; Dukes, Ellen; Hoffman, Deborah L; Tai, Kei-Sing; Stacey, Brett

    2005-10-01

    Our goal was to evaluate pain severity, pain-related interference with function, sleep impairment, symptom levels of anxiety and depression, and quality of life among patients with painful diabetic peripheral neuropathy (DPN). Participants in a burden of illness survey (n = 255) completed the modified Brief Pain Inventory-DPN (BPI-DPN), MOS Sleep Scale, Hospital Anxiety and Depression Scale (HADS), Short Form Health Survey-12v2 (SF-12v2), and the EuroQoL (EQ-5D). Patients were 61 +/- 12.8 years old (51.4% female), had diabetes for 12 +/- 10.3 years and painful DPN for 6.4 +/- 6.4 years. Average and Worst Pain scores (BPI-DPN, 0-10 scales) were 5.0 +/- 2.5 and 5.6 +/- 2.8. Pain substantially interfered (>or=4 on 0-10 scales) with walking ability, normal work, sleep, enjoyment of life, mood, and general activity. Moderate to severe symptom levels of anxiety and depression (HADS-A and HADS-D scores >or=11 on 0-21 scales) occurred in 35% and 28% of patients, respectively. Patients reported greater sleep problems compared with the general U.S. population and significant impairment in both physical and mental functioning (SF-12v2) compared with subjects with diabetes. The mean EQ-5D utility score was 0.5 +/- 0.3. Greater pain levels in DPN (mild to moderate to severe) corresponded with higher symptom levels of anxiety and depression, more sleep problems, and lower utility ratings and physical and mental functioning, (all Ps < 0.01). Painful DPN is associated with decrements in many aspects of patients' lives: physical and emotional functioning, affective symptoms, and sleep problems. The negative impact is higher in patients with greater pain severity. PMID:16256902

  6. Peripheral Neuropathy Due to Vitamin Deficiency, Toxins, and Medications

    PubMed Central

    Staff, Nathan P.; Windebank, Anthony J.

    2014-01-01

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

  7. Peripheral Neuropathy – Clinical and Electrophysiological Considerations

    PubMed Central

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

    2013-01-01

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

  8. Peripheral Neuropathy Associated withHypereosinophilic Syndrome

    PubMed Central

    Lee, Kyung Ho; Kim, Jung Eun

    2008-01-01

    The idiopathic hypereosinophilic syndrome (HES) represents a leukoproliferative disorder, characterized by unexplained prolonged eosinophilia (>6 months) and evidence of specific organ damage. So far, the peripheral neuropathy associated with skin manifestations of HES has not been reported in the dermatologic literature although the incidence of peripheral neuropathy after HES ranges from 6~52%. Herein, we report the peripheral neuropathy associated with HES, documented by clinical, histopathological, and electrodiagnostic criteria. PMID:27303181

  9. Surgical decompression in lower-extremity diabetic peripheral neuropathy.

    PubMed

    Rader, Andrew J

    2005-01-01

    Peripheral neuropathy can be a devastating complication of diabetes mellitus. This article describes surgical decompression as a means of restoring sensation and relieving painful neuropathy symptoms. A prospective study was performed involving patients diagnosed as having type 1 or type 2 diabetes with lower-extremity peripheral neuropathy. The neuropathy diagnosis was confirmed using quantitative sensory testing. Visual analog scales were used for subjective assessment before and after surgery. Treatment consisted of external and as-needed internal neurolysis of the common peroneal, deep peroneal, tibial, medial plantar, lateral plantar, and calcaneal nerves. Subjective pain perception and objective sensibility were significantly improved in most patients who underwent the described decompression. Surgical decompression of multiple peripheral nerves in the lower extremities is a valid and effective method of providing symptomatic relief of neuropathy pain and restoring sensation. PMID:16166461

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

    PubMed

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

    2014-01-01

    Peripheral neuropathy is a common and vexing symptom for people living with HIV infection (PLWH). Neuropathy occurs in several different syndromes and is identified in the literature as distal sensory polyneuropathy or distal sensory peripheral neuropathy. More recently, the HIV literature has focused on the syndrome as painful HIV-associated sensory neuropathy, addressing the symptom rather than the underlying pathophysiology. Assessment of neuropathy in PLWH is critical and must be incorporated into nursing practice for each visit. Neuropathy has been attributed to the direct effects of HIV, exposure to antiretroviral medications (particularly the nucleoside reverse transcriptase inhibitors), advanced immune suppression, and comorbid tuberculosis infection and exposure to antituberculosis medications. Evidence supports the importance of addressing neuropathy in PLWH with pharmacologic treatment regimens and complementary/alternative approaches. This paper examines the pathophysiology, evidence, and approaches to managing peripheral neuropathy. A case study has been included to illustrate a patient's experience with neuropathy symptoms. PMID:24698331

  11. Animal models for inherited peripheral neuropathies

    PubMed Central

    MARTINI, RUDOLF

    1997-01-01

    Recent progress in human genetics and neurobiology has led to the identification of various mutations in particular myelin genes as the cause for many of the known inherited demyelinating peripheral neuropathies. Mutations in 3 distinct myelin genes, PMP22, P0, and connexin 32 cause the 3 major demyelinating subtypes of Charcot-Marie-Tooth (CMT) disease, CMT1A, CMT1B and CMTX, respectively. In addition, a reduction in the gene dosage of PMP22 causes hereditary neuropathy with liability to pressure palsies (HNPP), while particular point mutations in PMP22 and P0 cause the severe Dejerine-Sottas (DS) neuropathy. A series of spontaneous and genetically engineered rodent mutants for genes for the above-mentioned myelin constituents are now available and their suitability to serve as models for these still untreatable diseases is an issue of particular interest. The spontaneous mutants Trembler-J and Trembler, with point mutations in PMP22, reflect some of the pathological alterations seen in CMT1A and DS patients, respectively. Furthermore, engineered mutants that either over or underexpress particular myelin genes are suitable models for patients who are similarly compromised in the gene dosage of the corresponding genes. In addition, engineered mutants heterozygously or homozygously deficient in the myelin component P0 show the pathology of distinct CMT1B and DS patients, respectively, while Cx32 deficient mice develop pathological abnormalities similar to those of CMTX patients. Mutants that mimic human peripheral neuropathies might allow the development of strategies to alleviate the symptoms of the diseases, and help to define environmental risk factors for aggravation of the disease. In addition, such mutants might be instrumental in the development of strategies to cure the diseases by gene therapy. PMID:9418989

  12. Animal models for inherited peripheral neuropathies.

    PubMed

    Martini, R

    1997-10-01

    Recent progress in human genetics and neurobiology has led to the identification of various mutations in particular myelin genes as the cause for many of the known inherited demyelinating peripheral neuropathies. Mutations in 3 distinct myelin genes, PMP22, P0, and connexin 32 cause the 3 major demyelinating subtypes of Charcot-Marie-Tooth (CMT) disease, CMT1A, CMT1B and CMTX, respectively. In addition, a reduction in the gene dosage of PMP22 causes hereditary neuropathy with liability to pressure palsies (HNPP), while particular point mutations in PMP22 and P0 cause the severe Dejerine-Sottas (DS) neuropathy. A series of spontaneous and genetically engineered rodent mutants for genes for the above-mentioned myelin constituents are now available and their suitability to serve as models for these still untreatable diseases is an issue of particular interest. The spontaneous mutants Trembler-J and Trembler, with point mutations in PMP22, reflect some of the pathological alterations seen in CMT1A and DS patients, respectively. Furthermore, engineered mutants that either over or underexpress particular myelin genes are suitable models for patients who are similarly compromised in the gene dosage of the corresponding genes. In addition, engineered mutants heterozygously or homozygously deficient in the myelin component P0 show the pathology of distinct CMT1B and DS patients, respectively, while Cx32 deficient mice develop pathological abnormalities similar to those of CMTX patients. Mutants that mimic human peripheral neuropathies might allow the development of strategies to alleviate the symptoms of the diseases, and help to define environmental risk factors for aggravation of the disease. In addition, such mutants might be instrumental in the development of strategies to cure the diseases by gene therapy. PMID:9418989

  13. Updates in diabetic peripheral neuropathy

    PubMed Central

    Juster-Switlyk, Kelsey; Smith, A. Gordon

    2016-01-01

    Diabetes has become one of the largest global health-care problems of the 21 st century. According to the Centers for Disease Control and Prevention, the population prevalence of diabetes in the US is approaching 10% and is increasing by 5% each year. Diabetic neuropathy is the most common complication associated with diabetes mellitus. Diabetes causes a broad spectrum of neuropathic complications, including acute and chronic forms affecting each level of the peripheral nerve, from the root to the distal axon. This review will focus on the most common form, distal symmetric diabetic polyneuropathy. There has been an evolution in our understanding of the pathophysiology and the management of diabetic polyneuropathy over the past decade. We highlight these new perspectives and provide updates from the past decade of research. PMID:27158461

  14. Animal models of HIV peripheral neuropathy

    PubMed Central

    Burdo, Tricia H; Miller, Andrew D

    2014-01-01

    The use of animal models in the study of HIV and AIDS has advanced our understanding of the underlying pathophysiologic mechanisms of infection. Of the multitude of HIV disease manifestations, peripheral neuropathy remains one of the most common long-term side effects. Several of the most important causes of peripheral neuropathy in AIDS patients include direct association with HIV infection with or without antiretroviral medication and infection with opportunistic agents. Because the pathogeneses of these diseases are difficult to study in human patients, animal models have allowed for significant advancement in the understanding of the role of viral infection and the immune system in disease genesis. This review focuses on rodent, rabbit, feline and rhesus models used to study HIV-associated peripheral neuropathies, focusing specifically on sensory neuropathy and antiretroviral-associated neuropathies. PMID:25214880

  15. Episodic neurological dysfunction in hereditary peripheral neuropathy

    PubMed Central

    Kulkarni, Girish Baburao; Mailankody, Pooja; Isnwara, Pawanraj Palu; Prasad, Chandrajit; Mustare, Veerendrakumar

    2015-01-01

    Episodic transient neurological symptoms are an important set of problems presenting to a neurologist in his routine practice. Occasionally, detailed clinical history including past and family history supplemented with focused examination can bring out a rare cause for such symptoms. We describe in this report in a young male presenting with episodic focal neurological dysfunction, with family history of similar episodes in mother and brother. Examination showed features of pes cavus and peripheral neuropathy for which patient was asymptomatic. Mother and brother were established cases of hereditary neuropathy. Imaging on multiple occasions showed reversible white matter abnormalities. Clinical suspicion of X-linked Charcot-Marie-Tooth disease type 1 (CMT1X) was confirmed with detection of mutation in Gap Junction B1 (GJB1) gene, which codes for connexin 32 protein (c.425G>A; p.R142Q hemizygous mutation). Though this mutation has been already reported in CMTX patients, it has not been associated with transient neurological dysfunctions. This is probably the first reported case of CMTX patient with transient neurological dysfunction from India, whose family members had similar episodes. PMID:25745327

  16. Familial multiple symmetric lipomatosis with peripheral neuropathy.

    PubMed

    Chalk, C H; Mills, K R; Jacobs, J M; Donaghy, M

    1990-08-01

    We describe coexisting peripheral neuropathy and multiple symmetric lipomatosis in 4 of 7 siblings. The absence of either condition in 3 other generations of this family suggests autosomal recessive inheritance. None of the affected siblings were alcoholic, a factor some have proposed to explain the frequent occurrence of peripheral neuropathy in sporadic multiple symmetric lipomatosis. Serum lipid studies, including apoprotein A levels, were normal. Sural nerve biopsy from 1 patient showed nerve fiber loss, predominantly affecting large myelinated fibers. The relationship between myelin sheath thickness and axon diameter was normal, arguing that this neuropathy is not due to primary axonal atrophy. PMID:2166247

  17. Drugs for the treatment of peripheral neuropathies.

    PubMed

    Marmiroli, Paola; Cavaletti, Guido

    2016-01-01

    Peripheral neuropathies are frequent in association with systemic diseases as well as isolated disorders. Recent advances in the therapy of specific neuropathies led to the approval of new drugs/treatments. This review selected those peripheral neuropathies where the most recent approvals were provided and revised the potential future developments in diabetic and toxic-induced neuropathies, although they do not have a currently available causal therapy in view of their epidemiological and social relevance. Data have been extracted from the most important published trials and from clinical experience. In addition, data from the Food and Drug Administration and European Medicine Agency indications on the treatment of the selected peripheral neuropathies and from recently updated international guidelines have also been included. The website of the U.S. National Institutes of Health www.clinicaltrials.gov registry has been used as the reference database for phase III clinical trials not yet published or ongoing. This review gives a general overview of the most recent advances in the treatment of amyloid, inflammatory, and paraproteinemic peripheral neuropathies. Moreover, it briefly describes the unmet medical need in disabling and frequent conditions, such as diabetic and chemotherapy-induced neuropathy, highlighting the most promising therapeutic approaches to their treatment. PMID:26567516

  18. Management of oxaliplatin-induced peripheral neuropathy

    PubMed Central

    Saif, M Wasif; Reardon, John

    2005-01-01

    Neurotoxicity is the most frequent dose-limiting toxicity of oxaliplatin. Acute sensory neurotoxicity manifests as rapid onset of cold-induced distal dysesthesia and/or paresthesia, sometimes accompanied by cold-dependent muscular contractions of the extremities or the jaw. The symptoms, often occurring during or shortly after infusion, are usually transient and mild. A cumulative sensory peripheral neuropathy may also develop with prolonged treatment with oxaliplatin, eventually causing superficial and deep sensory loss, sensory ataxia, and functional impairment. Studies have shown patients with acute sensory symptoms to display little or no axonal degeneration. The similarity of acute symptoms induced by oxaliplatin to those caused by several drugs or toxins acting on neuronal or muscular ion channels suggests that these symptoms may result from a specific interaction of oxaliplatin with voltage-gated sodium (Na+) channels. The current recommendations for the management of the acute and cumulative neurotoxicity from oxaliplatin include education about exposure to cold, dose modification, “stop and go”, and use of neuromodulatory agents, in particular, intravenous calcium and magnesium infusion. Upon the approval of oxaliplatin-based regimens both for adjuvant and metastatic treatment of colon cancer, it is crucial to compile knowledge about the recognition and management of neurotoxicity from oxaliplatin. PMID:18360567

  19. Peripheral Neuropathy in Rats Exposed to Dichloroacetate

    PubMed Central

    Calcutt, Nigel A.; Lopez, Veronica L.; Bautista, Arjel D.; Mizisin, Leah M.; Torres, Brenda R.; Shroads, Albert L.; Mizisin, Andrew P.; Stacpoole, Peter W.

    2009-01-01

    The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50–500 mg/kg/day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats. No overt axonal or glial cell abnormalities were identified in peripheral nerves or spinal cord of any DCA-treated rats but morphometric analysis identified a reduction of mean axonal caliber of peripheral nerve myelinated fibers. DCA treatment also caused accumulation of oxidative stress markers in the nerves. These data indicate that behavioral, functional and structural indices of peripheral neuropathy may be induced in both juvenile and adult rats treated with DCA at doses similar to those in clinical use. DCA-induced peripheral neuropathy primarily afflicts axons and involves both metabolic and structural disorders. The DCA-treated rat may provide insight into the pathogenesis of peripheral neuropathy and facilitate development of adjuvant therapeutics to prevent this disorder that currently restricts the clinical use of DCA. PMID:19680144

  20. Mitotoxicity in distal symmetrical sensory peripheral neuropathies

    PubMed Central

    Bennett, Gary J.; Doyle, Timothy; Salvemini, Daniela

    2016-01-01

    Chronic distal symmetrical sensory peripheral neuropathy is a common neurological complication of cancer chemotherapy, HIV treatment and diabetes. Although aetiology-specific differences in presentation are evident, the clinical signs and symptoms of these neuropathies are clearly similar. Data from animal models of neuropathic pain suggest that the similarities have a common cause: mitochondrial dysfunction in primary afferent sensory neurons. Mitochondrial dysfunction is caused by mitotoxic effects of cancer chemotherapeutic drugs of several chemical classes, HIV-associated viral proteins, and nucleoside reverse transcriptase inhibitor treatment, as well as the (possibly both direct and indirect) effects of excess glucose. The mitochondrial injury results in a chronic neuronal energy deficit, which gives rise to spontaneous nerve impulses and a compartmental neuronal degeneration that is first apparent in the terminal receptor arbor—that is, intraepidermal nerve fibres—of cutaneous afferent neurons. Preliminary data suggest that drugs that prevent mitochondrial injury or improve mitochondrial function could be useful in the treatment of these conditions. PMID:24840972

  1. Peripheral Neuropathy in Mouse Models of Diabetes.

    PubMed

    Jolivalt, Corinne G; Frizzi, Katie E; Guernsey, Lucie; Marquez, Alex; Ochoa, Joseline; Rodriguez, Maria; Calcutt, Nigel A

    2016-01-01

    Peripheral neuropathy is a frequent complication of chronic diabetes that most commonly presents as a distal degenerative polyneuropathy with sensory loss. Around 20% to 30% of such patients may also experience neuropathic pain. The underlying pathogenic mechanisms are uncertain, and therapeutic options are limited. Rodent models of diabetes have been used for more than 40 years to study neuropathy and evaluate potential therapies. For much of this period, streptozotocin-diabetic rats were the model of choice. The emergence of new technologies that allow relatively cheap and routine manipulations of the mouse genome has prompted increased use of mouse models of diabetes to study neuropathy. In this article, we describe the commonly used mouse models of type 1 and type 2 diabetes, and provide protocols to phenotype the structural, functional, and behavioral indices of peripheral neuropathy, with a particular emphasis on assays pertinent to the human condition. © 2016 by John Wiley & Sons, Inc. PMID:27584552

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

    PubMed Central

    Addington, James; Freimer, Miriam

    2016-01-01

    Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects. PMID:27408692

  3. Abnormal calcium homeostasis in peripheral neuropathies

    PubMed Central

    Fernyhough, Paul; Calcutt, Nigel A.

    2010-01-01

    Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The central impact of both alterations of Ca2+ signalling at the plasma membrane and also intracellular Ca2+ handling on sensory neuron function is discussed and related to abnormal endoplasmic reticulum performance. We also present new data highlighting sub-optimal axonal Ca 2+ signalling in diabetic neuropathy and discuss the putative role for this abnormality in the induction of axonal degeneration in peripheral neuropathies. The accumulating evidence implicating Ca2+ dysregulation with both painful and degenerative neuropathies, along with recent advances in understanding of regional variations in Ca2+ channel and pump structures, makes modulation of neuronal Ca2+ handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many peripheral neuropathies. PMID:20034667

  4. Expenditures in the elderly with peripheral neuropathy

    PubMed Central

    Callaghan, Brian C.; Burke, James F.; Rodgers, Ann; McCammon, Ryan; Langa, Kenneth M.; Feldman, Eva L.; Kerber, Kevin A.

    2013-01-01

    Summary To optimize care in the evaluation of peripheral neuropathy, we sought to define which tests drive expenditures and the role of the provider type. We investigated test utilization and expenditures by provider type in those with incident neuropathy in a nationally representative elderly, Medicare population. Multivariable logistic regression was used to determine predictors of MRI and electrodiagnostic utilization. MRIs of the neuroaxis and electrodiagnostic tests accounted for 88% of total expenditures. Mean and aggregate diagnostic expenditures were higher in those who saw a neurologist. Patients who saw a neurologist were more likely to receive an MRI and an electrodiagnostic test. MRIs and electrodiagnostic tests are the main contributors to expenditures in the evaluation of peripheral neuropathy, and should be the focus of future efficiency efforts. PMID:24175158

  5. [Colonic Crohn's disease complicated with peripheral neuropathy].

    PubMed

    Chaoui, F; Hellal, H; Balamane, M; Boudhane, M; Mikol, J; Masmoudi, A

    1990-01-01

    The association of Crohn's disease and peripheral neuropathy is a rare event and the pathogenic factors often implicated are vitamin B12 deficiency or metronidazole treatment. We report a case of severe axonal polyneuropathy associated with Crohn's disease and unrelated to vitamin deficiency or metronidazole treatment. This represents a very rare extra-digestive manifestation of Crohn's disease. PMID:2125951

  6. Prevalence of peripheral neuropathy and painful peripheral neuropathy in Turkish diabetic patients.

    PubMed

    Erbas, Tomris; Ertas, Mustafa; Yucel, Aysen; Keskinaslan, Abdulkadir; Senocak, Mustafa

    2011-02-01

    The aim of this study was to determine the prevalence of diabetic peripheral neuropathy (DPN) and neuropathic pain in diabetic patients attending university outpatient clinics in Turkey. In this multicenter cross-sectional study, neurologic examinations and nerve conduction studies along with clinical diabetic neuropathy score, and Leeds Assessment of Neuropathic Symptoms and Signs pain scale were performed on 1,113 patients (46.2% male) from 14 centers. Prevalence of DPN determined only by clinical examination was 40.4% and increased to 62.2%, by combining nerve conduction studies with clinical examination. According to Leeds Assessment of Neuropathic Symptoms and Signs scores, neuropathic pain prevalence was 16.0% in those who reported pain. Poor glycemic control, retinopathy, microalbuminuria, hyperlipidemia, diabetic foot, and foot amputation were more commonly observed in patients with DPN. Clinical DPN affected 40.4% of diabetic patients, and neuropathic pain prevalence in diabetic patient population was 14.0%. Clinical examinations and nerve conduction studies are important components for early detection and accurate diagnosis of DPN and painful DPN. PMID:21221008

  7. Peripheral neuropathy induced by combination chemotherapy of docetaxel and cisplatin.

    PubMed Central

    Hilkens, P. H.; Pronk, L. C.; Verweij, J.; Vecht, C. J.; van Putten, W. L.; van den Bent, M. J.

    1997-01-01

    Docetaxel, a new semisynthetic taxoid that has demonstrated promising activity as an antineoplastic agent, was administered in combination with cisplatin to 63 patients in a dose-escalating study. As both drugs were known to be potentially neurotoxic, peripheral neurotoxicity was prospectively assessed in detail. Neuropathy was evaluated by clinical sum-score for signs and symptoms and by measurement of the vibration perception threshold (VPT). The severity of neuropathy was graded according to the National Cancer Institute's 'Common Toxicity Criteria'. The docetaxel-cisplatin combination chemotherapy induced a predominantly sensory neuropathy in 29 (53%) out of 55 evaluable patients. At cumulative doses of both cisplatin and docetaxel above 200 mg m(-2), 26 (74%) out of 35 patients developed a neuropathy which was mild in 15, moderate in ten and severe in one patient. Significant correlations were present between both the cumulative dose of docetaxel and cisplatin and the post-treatment sum-score of neuropathy (P < 0.01) as well as the post-treatment VPT (P < 0.01). The neurotoxic effects of this combination were more severe than either cisplatin or docetaxel as single agent at similar doses. PMID:9020489

  8. Computer aided diagnosis of diabetic peripheral neuropathy

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  9. [Peripheral neuropathy occurring soon after cord blood transplantation].

    PubMed

    Harada, Sakiko; Hayashi, Hiromi; Tadera, Noriyuki; Iwama, Kannichi; Kajiwara, Kouichi; Kouzai, Yasuji; Koudo, Hideki

    2016-04-01

    We experienced two cases of peripheral neuropathy in the early phase following cord blood transplantation. Case 1 was a 66-year-old man with recurrent T-ALL. On day 8, he experienced a sharp pain originating in both the palms and the soles, which worsened spreading to the knees, and was accompanied by muscle weakness. The neurological symptom progressed to the point of being unable to walk. A nerve conduction velocity test showed demyelination and axonopathy. In the CSF analysis, albuminocytologic dissociation and a rise in myelin basic protein were detected. These findings met the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). The symptoms improved with intravenous immunoglobulin (IVIG). He is now able to walk and continues to visit our department. Case 2 was a 42-year-old man with primary mediastinal large B-cell lymphoma. As the disease was refractory, he underwent reduced intensity cord blood transplantation (RICBT). Flare and numbness started in the palms and soles on day 26, with the symptoms progressing thereafter. A nerve conduction velocity test showed demyelination and axonopathy. The symptoms improved after IVIG administration. The diagnosis of peripheral neuropathy after transplantation is often difficult, but when an immunologic disorder is suspected to be the cause, early administration of IVIG may be effective. PMID:27169453

  10. 77 FR 47795 - Disease Associated With Exposure to Certain Herbicide Agents: Peripheral Neuropathy

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-10

    ... herbicide exposure and the occurrence of ``acute and subacute transient peripheral neuropathy.'' In... established a regulatory presumption of service connection for ``acute and subacute peripheral neuropathy...'s current regulation presumes service connection for ``acute and subacute peripheral...

  11. Inherited peripheral neuropathies due to mitochondrial disorders.

    PubMed

    Cassereau, J; Codron, P; Funalot, B

    2014-05-01

    Mitochondrial disorders (MIDs) are frequently responsible for neuropathies with variable severity. Mitochondrial diseases causing peripheral neuropathies (PNP) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. The last years have seen a growing list of evidence demonstrating that mitochondrial bioenergetics and dynamics might be dysfunctional in axonal Charcot-Marie-Tooth disease (CMT2), and these mechanisms might present a common link between dissimilar CMT2-causing genes. PMID:24768438

  12. Opioid overdose with gluteal compartment syndrome and acute peripheral neuropathy

    PubMed Central

    Adrish, Muhammad; Duncalf, Richard; Diaz-Fuentes, Gilda; Venkatram, Sindhaghatta

    2014-01-01

    Patient: Male, 42 Final Diagnosis: Gluteal compartment syndrome • acute peripheral nauropathy Symptoms: — Medication: — Clinical Procedure: — Specialty: Critical Care Medicine Objective: Management of emergency care Background: Heroin addiction is common, with an estimated 3.7 million Americans reporting to have used it at some point in their lives. Complications of opiate overdose include infection, rhabdomyolysis, respiratory depression and central or peripheral nervous system neurological complications. Conclusions: We present a 42-year-old male admitted after heroin use with heroin-related peripheral nervous system complication preceded by an acute gluteal compartment syndrome and severe rhabdomyolysis. Case Report: Early diagnosis and surgical intervention of the compartment syndrome can lead to full recovery while any delay in management can be devastating and can lead to permanent disability. The presence of peripheral nervous system injuries may portend a poor prognosis and can also lead to long term disability. Careful neurological evaluation for signs and symptoms of peripheral nervous system injuries is of paramount importance, as these may be absent at presentation in patients with opioid overdose. There is a potential risk of delaying a necessary treatment like fasciotomy in these patients by falsely attributing clinical symptoms to a preexisting neuropathy. Early EMG and nerve conduction studies should be considered when the etiology of underlying neurological weakness is unclear. PMID:24459539

  13. Chemotherapy-Induced Peripheral Neuropathy in Pediatric Cancer Patients

    PubMed Central

    Groninger, Hunter

    2014-01-01

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

  14. Chemotherapy-induced Peripheral Neuropathy | Division of Cancer Prevention

    Cancer.gov

    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). |

  15. [Peripheral neuropathies due to mitochondrial disorders].

    PubMed

    Funalot, B

    2009-12-01

    Involvement of peripheral nerves is frequent in mitochondrial disorders but with variable severity. Mitochondrial diseases causing peripheral neuropathies (PN) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. Genetically-determined PN due to mutations of mitofusin 2, a GTPase involved in the fusion of external mitochondrial membranes, were identified during the last few years. Characteristic ultrastructural lesions (abnormalities of axonal mitochondria) are observed on longitudinal sections of nerve biopsies in patients with PN due to mitofusin 2 mutations. PMID:19942242

  16. Treating Painful Diabetic Peripheral Neuropathy: An Update.

    PubMed

    Snyder, Matthew J; Gibbs, Lawrence M; Lindsay, Tammy J

    2016-08-01

    Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient's goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use. PMID:27479625

  17. Mechanisms of distal axonal degeneration in peripheral neuropathies.

    PubMed

    Cashman, Christopher R; Höke, Ahmet

    2015-06-01

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

  18. Mechanisms of Distal Axonal Degeneration in Peripheral Neuropathies

    PubMed Central

    Cashman, Christopher R.; Höke, Ahmet

    2015-01-01

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

  19. Peripheral neuropathy after occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    PubMed

    Sweeney, M H; Fingerhut, M A; Arezzo, J C; Hornung, R W; Connally, L B

    1993-06-01

    Reports of human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) describe signs and symptoms consistent with exposure-related peripheral neuropathy. In a cross-sectional study, prevalence of peripheral neuropathy was measured in 265 workers exposed 15 years earlier to chemicals contaminated with TCDD and in 244 unexposed, age-, race-, gender- and community-matched comparisons. Cases of peripheral neuropathy were defined from examination, electrophysiologic and quantitative sensory tests, and symptoms. Exposure was assessed by measuring lipid-adjusted serum TCDD levels. The mean serum TCDD level for workers (220 parts per trillion (ppt)) was significantly higher than for referents (7 ppt) (p < .0001). Thirty-two percent of both worker and referent groups met the case definition for peripheral neuropathy. In the logistic regression analyses, serum TCDD level was not related to peripheral neuropathy. These data suggest that despite continued high serum TCDD levels, peripheral neuropathy is not a long-term sequela of high exposure to TCDD-contaminated chemicals. However, the study cannot preclude the occurrence and subsequent resolution of acute effects caused by high exposure, as experienced in Seveso and possibly by some workers, while exposed to high levels of TCDD-contaminated substances. PMID:8392292

  20. Diagnosis and therapeutic options for peripheral vasculitic neuropathy.

    PubMed

    Blaes, Franz

    2015-04-01

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

  1. Diagnosis and therapeutic options for peripheral vasculitic neuropathy

    PubMed Central

    2015-01-01

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

  2. Myanmarese Neuropathy: Clinical Description of Acute Peripheral Neuropathy Detected among Myanmarese Refugees in Malaysia.

    PubMed

    Fu Liong, Hiew; Santhi, Datuk Puvanarajah; Shanthi, Viswanathan; Mohd Hanip, Rafia

    2014-01-01

    Background. Since 2008, we have observed an increasing number of Myanmarese refugees in Malaysia being admitted for acute/subacute onset peripheral neuropathy. Most of them had a preceding history of starvation. Methods. We retrospectively studied the clinical features of all Myanmarese patients admitted with peripheral neuropathy from September 2008 to January 2014. Results. A total of 24 patients from the Chin, Rohingya, and Rakhine ethnicities (mean age, 23.8 years; male, 96%) had symmetrical, ascending areflexic weakness with at least one additional presenting symptom of fever, lower limb swelling, vomiting, abdominal pain, or difficulty in breathing. Twenty (83.3%) had sensory symptoms. Ten (41.6%) had cranial nerve involvement. Nineteen patients had cerebrospinal fluid examinations but none with evidence of albuminocytological dissociation. Neurophysiological assessment revealed axonal polyneuropathy, predominantly a motor-sensory subtype. Folate and vitamin B12 deficiencies were detected in 31.5% of them. These findings suggested the presence of a polyneuropathy related to nutrition against a backdrop of other possible environmental factors such as infections, metabolic disorders, or exposure to unknown toxin. Supportive treatment with appropriate vitamins supplementation improved functional outcome in most patients. Conclusion. We report a spectrum of acquired reversible neurological manifestations among Myanmarese refugees likely to be multifactorial with micronutrient deficiencies playing an important role in the pathogenesis. PMID:27350989

  3. Myanmarese Neuropathy: Clinical Description of Acute Peripheral Neuropathy Detected among Myanmarese Refugees in Malaysia

    PubMed Central

    Santhi, Datuk Puvanarajah; Mohd Hanip, Rafia

    2014-01-01

    Background. Since 2008, we have observed an increasing number of Myanmarese refugees in Malaysia being admitted for acute/subacute onset peripheral neuropathy. Most of them had a preceding history of starvation. Methods. We retrospectively studied the clinical features of all Myanmarese patients admitted with peripheral neuropathy from September 2008 to January 2014. Results. A total of 24 patients from the Chin, Rohingya, and Rakhine ethnicities (mean age, 23.8 years; male, 96%) had symmetrical, ascending areflexic weakness with at least one additional presenting symptom of fever, lower limb swelling, vomiting, abdominal pain, or difficulty in breathing. Twenty (83.3%) had sensory symptoms. Ten (41.6%) had cranial nerve involvement. Nineteen patients had cerebrospinal fluid examinations but none with evidence of albuminocytological dissociation. Neurophysiological assessment revealed axonal polyneuropathy, predominantly a motor-sensory subtype. Folate and vitamin B12 deficiencies were detected in 31.5% of them. These findings suggested the presence of a polyneuropathy related to nutrition against a backdrop of other possible environmental factors such as infections, metabolic disorders, or exposure to unknown toxin. Supportive treatment with appropriate vitamins supplementation improved functional outcome in most patients. Conclusion. We report a spectrum of acquired reversible neurological manifestations among Myanmarese refugees likely to be multifactorial with micronutrient deficiencies playing an important role in the pathogenesis. PMID:27350989

  4. Animal models of peripheral neuropathy due to environmental toxicants.

    PubMed

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

    2014-01-01

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

  5. Peripheral neuropathies of rheumatologic disease and gluten-related disorders.

    PubMed

    Reda, Haatem; Chin, Russell L

    2014-09-01

    Peripheral nervous system disease is a common and often debilitating feature of many systemic rheumatologic disorders. Such involvement takes many forms, reflecting the variety of underlying pathophysiology, though most patients present with painful multifocal neuropathy (usually vasculitic) or a distal sensory more than motor peripheral neuropathy (sometimes vasculitic and nearly always axonal). The presence of peripheral nervous system involvement is often an early signal of the generalization of inflammatory disease in blood vessels or extravascular tissues, though peripheral neuropathy is not itself an independent predictor of mortality. Nonetheless, progressive multifocal neuropathy, motor neuropathy, small fiber neuropathy, and sensory neuronopathy should be treated early and aggressively with immunosuppression (or the gluten-free diet in appropriate situations) to limit morbidity. Given the rapidly evolving therapeutic landscape, partnership with a rheumatologist is essential. Treatment is usually sustained for 1 to 2 years, and remission is possible in many cases within 6 to 12 months, with variable rates of relapse and treatment resistance. Patients should be meticulously monitored for relapse with serial laboratory testing, electrodiagnostic studies, and clinical examination. Functional rating scores, such as the neuropathy impairment scale and the total neuropathy score are useful for longitudinal assessment. PMID:25369437

  6. Animal Models of Peripheral Neuropathy Due to Environmental Toxicants

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Salehi, Zeinab; Roayaei, Mahnaz

    2015-01-01

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

  8. Recent Advances in Diagnostic Strategies for Diabetic Peripheral Neuropathy

    PubMed Central

    2016-01-01

    Diabetes is an increasing epidemic in Korea, and associated diabetic peripheral neuropathy (DPN) is its most common and disabling complication. DPN has an insidious onset and heterogeneous clinical manifestations, making it difficult to detect high-risk patients of DPN. Early diagnosis is recommended and is the key factor for a better prognosis and preventing diabetic foot ulcers, amputation, or disability. However, diagnostic tests for DPN are not clearly established because of the various pathophysiology developing from the nerve injury to clinical manifestations, differences in mechanisms according to the type of diabetes, comorbidities, and the unclear natural history of DPN. Therefore, DPN remains a challenge for physicians to screen, diagnose, follow up, and evaluate for treatment response. In this review, diagnosing DPN using various methods to assess clinical symptoms and/or signs, sensorineural impairment, and nerve conduction studies will be discussed. Clinicians should rely on established modalities and utilize current available testing as complementary to specific clinical situations. PMID:27246283

  9. [Nursing care of chemotherapy-induced peripheral neuropathy].

    PubMed

    Hsu, Shu-Yi; Lu, Chang-Hsien; Chen, Shu-Zhen; Jane, Sui-Whi

    2015-04-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event occurring in patients who receive neurotoxic chemotherapeutic agents such as taxanes, platinum, and vinca alkaloids. The manifestations of CIPN include intolerable symmetric numbness, burning and tingling in distal limbs, disruption of daily functions, reduced quality of life, and the reduction in dosage or discontinued use of these agents. There is a paucity of articles on nursing care related to CIPN in the literature. This article reviews the pathophysiology, clinical presentation, diagnostic criteria, medical management and nursing care of CIPN. Review findings are intended to help nurses identify high-risk groups in order to implement preventive measures that strengthen the muscles, train the balance, and initiate falling precautions of persons in this population. Timely preventive measures may effectively alleviate CIPN symptoms and assure the safety and overall quality of life of patients. PMID:25854951

  10. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN)

    PubMed Central

    Han, Yaqin; Smith, Maree T.

    2013-01-01

    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. PMID:24385965

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

    PubMed

    Ogata, Katsuhisa

    2016-03-01

    Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course. PMID:27001769

  12. Chronic demyelinating peripheral neuropathy in cerebrotendinous xanthomatosis.

    PubMed

    Argov, Z; Soffer, D; Eisenberg, S; Zimmerman, Y

    1986-07-01

    Three siblings with chemically proved cerebrotendinous xanthomatosis presented with typical neurological manifestations of dementia and spinocerebellar disorder. Electrodiagnostic tests revealed demyelinating neuropathy in all three. Sural nerve biopsies showed loss of myelinated large fibers, marked Schwann cell proliferation, and onion bulb formation. Teased-fiber preparations confirmed the occurrence of segmental demyelination and remyelination. We suggest that demyelinating neuropathy is part of the neurological spectrum of cerebrotendinous xanthomatosis and should be considered in the differential diagnosis of a recessively inherited motor and sensory neuropathy. PMID:3017187

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-07-01

    Chemotherapy-induced neuropathy is a painful and debilitating adverse effect of certain chemotherapy drugs. There have not been any patient-centered, easily accessible Web-based interventions to assist with self-management of chemotherapy-induced neuropathy. The aims of this study were to evaluate usability and acceptability and to estimate an effect size of a Web-based intervention for assessing and managing chemotherapy-induced neuropathy. Participants (N = 14) were instructed to complete the Creativity, Optimism, Planning, and Expert Information for Chemotherapy-Induced Peripheral Neuropathy program and provide verbal responses to the program. Participants completed the Chemotherapy Induced Peripheral Neuropathy Assessment Tool and Post-Study System Usability Questionnaire. Iterative changes were made to the COPE-CIPN. Participants were asked to provide feedback on the revised COPE-CIPN, repeat the Chemotherapy Induced Peripheral Neuropathy Assessment Tool, and evaluate acceptability using the Acceptability e-Scale. The COPE-CIPN demonstrated high usability (mean, 1.98 [SD, 1.12]) and acceptability (mean, 4.40 [SD, 0.52]). Comments indicated that the interface was easy to use, and the information was helpful. While neuropathy symptoms continued to increase in this group of patients receiving neurotoxic chemotherapy, there was a decrease in mean level of interference with activities from 53.71 to 39.29 over 3 to 4 months, which indicated a moderate effect (d = 0.39) size. The COPE-CIPN may be a useful intervention to support self-management of chemotherapy-induced neuropathy. PMID:27116414

  15. Peripheral Neuropathy Associated With Novel Therapies in Patients With Multiple Myeloma: Consensus Statement of the IMF Nurse Leadership Board

    PubMed Central

    Tariman, Joseph D.; Love, Ginger; McCullagh, Emily; Sandifer, Stacey

    2014-01-01

    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. PMID:18490255

  16. Diabetic Peripheral Neuropathy: Should a Chaperone Accompany Our Therapeutic Approach?

    PubMed Central

    Farmer, Kevin L.; Li, Chengyuan

    2012-01-01

    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

  17. Goshajinkigan reduces oxaliplatin-induced peripheral neuropathy without affecting anti-tumour efficacy in rodents.

    PubMed

    Ushio, Soichiro; Egashira, Nobuaki; Sada, Hikaru; Kawashiri, Takehiro; Shirahama, Masafumi; Masuguchi, Ken; Oishi, Ryozo

    2012-06-01

    Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Goshajinkigan (GJG) is a Kampo medicine that is used for the treatments of several neurological symptoms including pain and numbness. More recently, GJG has been reported to prevent the oxaliplatin-induced peripheral neuropathy in clinical studies. No experimental study, however, has been conducted to date to determine the effect of GJG on pain behaviour in a rat model of oxaliplatin-induced neuropathy. Moreover, the impact on the anti-tumour effect of oxaliplatin remains unknown. In the present study, we examined the effects of GJG on the peripheral neuropathy and anti-tumour activity of oxaliplatin in rodents. Repeated administration of oxaliplatin caused cold hyperalgesia from days 3 to 37 and mechanical allodynia from days 21 to 28. Repeated administration of GJG prevented the oxaliplatin-induced cold hyperalgesia but not mechanical allodynia and axonal degeneration in rat sciatic nerve. Single administration of GJG reduced both cold hyperalgesia and mechanical allodynia after the development of neuropathy. In addition, GJG did not affect the anti-tumour effect of oxaliplatin in the tumour cells or tumour cells-implanted mice. These results suggest that GJG relieves the oxaliplatin-induced cold hyperalgesia and mechanical allodynia without affecting anti-tumour activity of oxaliplatin, and, therefore, may be useful for the oxaliplatin-induced neuropathy in clinical practice. PMID:21907570

  18. An Early Diagnostic Tool for Diabetic Peripheral Neuropathy in Rats

    PubMed Central

    Kambiz, Shoista; van Neck, Johan W.; Cosgun, Saniye G.; van Velzen, Marit H. N.; Janssen, Joop A. M. J. L.; Avazverdi, Naim; Hovius, Steven E. R.; Walbeehm, Erik T.

    2015-01-01

    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 investigate whether the skin rewarming rate in diabetic rats is related to microvascular changes and whether this is accompanied by changes observed in classical 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. Peripheral neuropathy was determined by the density of intra-epidermal nerve fibers (IENFs), mechanical sensitivity, and electrophysiological recordings. Data were obtained in diabetic rats at four, six, and eight weeks after the induction of diabetes and in controls. Four weeks after the induction of diabetes, a delayed rewarming rate, decreased skin blood flow and decreased density of IENFs were observed. However, the mechanical hyposensitivity and decreased motor nerve conduction velocity (MNCV) developed 6 and 8 weeks after the induction of diabetes. Our study shows that the skin rewarming rate is related to microvascular changes in diabetic rats. Moreover, the skin rewarming rate is a non-invasive method that provides more information for an earlier diagnosis of peripheral neuropathy than the classical monofilament test and MNCV in STZ induced diabetic rats. PMID:25984949

  19. HIV peripheral neuropathy and foot care management: a review of assessment and relevant guidelines.

    PubMed

    Anastasi, Joyce K; Capili, Bernadette; Chang, Michelle

    2013-12-01

    Despite the decline in the incidence of central nervous system disease associated with HIV, distal sensory peripheral (DSP) neuropathy continues to be prevalent in this population, causing debilitating symptoms and affecting quality of life. Patients typically present with numbness, tingling, burning pain, and loss of sensation in the toes and soles of their feet. Although this complication causes loss of protective function and puts patients at elevated risk for injury, infection, and falls, foot care for people with HIV is often overlooked. This article reviews what is known about DSP neuropathy in HIV and discusses relevant foot care guidelines, adopted from the literature on other conditions associated with neuropathic foot disorders. PMID:24247663

  20. Image analysis software for following progression of peripheral neuropathy

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  1. Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy.

    PubMed

    Kagiava, Alexia; Sargiannidou, Irene; Theophilidis, George; Karaiskos, Christos; Richter, Jan; Bashiardes, Stavros; Schiza, Natasa; Nearchou, Marianna; Christodoulou, Christina; Scherer, Steven S; Kleopa, Kleopas A

    2016-04-26

    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. PMID:27035961

  2. Profound and persistent painful paclitaxel peripheral neuropathy in a premenopausal patient

    PubMed Central

    Quintyne, K I; Mainstone, P; McNamara, B; Boers, P; Wallis, F; Gupta, R K

    2011-01-01

    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. PMID:22696717

  3. Chemotherapy-induced peripheral neuropathies in hematological malignancies.

    PubMed

    Jongen, Joost Louis Marie; Broijl, Annemiek; Sonneveld, Pieter

    2015-01-01

    Recent developments in the treatment of hematological malignancies, especially with the advent of proteasome inhibitors and immunomodulatory drugs in plasma cell dyscrasias, call for an increased collaboration between hematologists and neurologists. This collaboration involves differentiating chemotherapy-induced peripheral neuropathies (CiPN) from disease-related neurologic complications, early recognition of CiPN and treatment of neuropathic pain. Multiple myeloma, Waldenstrom's macroglobulinemia and light-chain amyloidosis frequently present with peripheral neuropathy. In addition, multiple myeloma, non-Hodgkin lymphomas and leukemia's may mimic peripheral neuropathy by compression or invasion of the extra/intradural space. Platinum compounds, vinca alkaloids, proteasome inhibitors and immunomodulatory drugs may all cause CiPN, each with different and often specific clinical characteristics. Early recognition, by identifying the distinct clinical phenotype of CiPN, is of crucial importance to prevent irreversible neurological damage. No recommendations can be given on the use of neuroprotective strategies because of a lack of convincing clinical evidence. Finally, CiPN caused by vinca-alkaloids, proteasome inhibitors and immunomodulatory drugs is often painful and neurologists are best equipped to treat this kind of painful neuropathy. PMID:25326770

  4. Experimental diabetes in neonatal mice induces early peripheral sensorimotor neuropathy.

    PubMed

    Ariza, L; Pagès, G; García-Lareu, B; Cobianchi, S; Otaegui, P J; Ruberte, J; Chillón, M; Navarro, X; Bosch, A

    2014-08-22

    Animal models of diabetes do not reach the severity of human diabetic neuropathy but relatively mild neurophysiological deficits and minor morphometric changes. The lack of degenerative neuropathy in diabetic rodent models seems to be a consequence of the shorter length of the axons or the shorter animal life span. Diabetes-induced demyelination needs many weeks or even months before it can be evident by morphometrical analysis. In mice myelination of the peripheral nervous system starts at the prenatal period and it is complete several days after birth. Here we induced experimental diabetes to neonatal mice and we evaluated its effect on the peripheral nerve 4 and 8 weeks after diabetes induction. Neurophysiological values showed a decline in sensory nerve conduction velocity at both time-points. Morphometrical analysis of the tibial nerve demonstrated a decrease in the number of myelinated fibers, fiber size and myelin thickness at both time-points studied. Moreover, aldose reductase and poly(ADP-ribose) polymerase activities were increased even if the amount of the enzyme was not affected. Thus, type 1 diabetes in newborn mice induces early peripheral neuropathy and may be a good model to assay pharmacological or gene therapy strategies to treat diabetic neuropathy. PMID:24846610

  5. Progress in the treatment of small fiber peripheral neuropathy.

    PubMed

    Chiang, Ming-Chang; Tseng, Ming-Tsung; Pan, Chun-Liang; Chao, Chi-Chao; Hsieh, Sung-Tsang

    2015-03-01

    Small fiber neuropathy is a syndrome of diverse disease etiology because of multiple pathophysiologic mechanisms with major presentations of neuropathic pain and autonomic symptoms. Over the past decade, there has been substantial progress in the treatments for neuropathic pain, dysautonomia and disease-modifying strategy. In particular, anticonvulsants and antidepressants alleviate neuropathic pain based on randomized clinical trials. PMID:25664678

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

    PubMed

    Brunelli, Brian; Gorson, Kenneth C

    2004-03-15

    Complementary and alternative medicine (CAM) therapies have become increasingly popular and are used regularly by patients with chronic neurological disorders. The prevalence and characteristics of CAM use by patients with peripheral neuropathy is unknown. We performed a prospective, questionnaire-based study to determine the prevalence and patterns of use of CAM therapies in 180 consecutive outpatients with peripheral neuropathy. The use of CAM was reported by 77 patients (43%) with neuropathy. The most frequent were megavitamins (35%), magnets (30%), acupuncture (30%), herbal remedies (22%), and chiropractic manipulation (21%); 37 (48%) tried more than one form of alternative treatment. Seventeen respondents (27%) thought their neuropathy symptoms improved with these approaches. Those who used CAM were slightly younger (mean age 62 vs. 65 years, p = 0.05) and more often college educated (39% vs. 24%, p = 0.03) compared to CAM nonusers. They also more often reported burning neuropathic pain (62% vs. 44%, p = 0.01). Patients with diabetic neuropathy used CAM more frequently than others (p = 0.03). The most common reason for using CAM was inadequate pain control (32%). Almost half of patients did not consult a physician before starting CAM. We conclude that there is a high prevalence of CAM use in our patients with neuropathy, and one-quarter reported that their symptoms improved. CAM users were better educated than nonusers, but most did not discuss CAM treatments with their physician. Neuropathic pain was substantially more common in CAM users, and lack of pain control was the most common reason for CAM use. PMID:14759634

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

    PubMed Central

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

    2013-01-01

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

  8. Sharpening the Tandem Walking Test for Screening Peripheral Neuropathy

    PubMed Central

    Cohen, Helen S.; Mulavara, Ajitkumar P.; Peters, Brian T.; Sangi-Haghpeykar, Haleh; Kung, Doris H.; Mosier, Dennis R.; Bloomberg, Jacob J.

    2013-01-01

    Objective Few tests of functional motor behavior are useful for rapidly screening people for lower extremity peripheral neuropathy. The goal of this study was to improve the widely used Tandem Walking test (TW). Methods We tested adult normals and ambulatory peripheral neuropathy patients (PN) with eyes open and eyes closed, while they performed TW on industrial carpeting, in sock-covered feet. Each subject wore a torso-mounted inertial motion unit to measure kinematic data. PN subjects’ data were also compared to historical data on patients with vestibular impairments (VI). Results The normal and PN groups differed significantly on TW on the number of steps completed. PN and VI data also differed significantly on both visual conditions. Kinematic data showed that PN patients were more unstable than normals. For the number of steps taken during the eyes open condition receiver operating characteristic (ROC) values were only 0.81. For the number of steps taken during the eyes closed condition, however, ROC=0.88. Although not optimal, this ROC value is better. Sensitivity and specificity at a cut-off of 2 steps were 0.81 and 0.92, respectively, and at a cut-off of 3 steps was 0.86 and 0.75, respectively. ROC values for kinematic data were all < 0.8 and, when combined with the ROC value for the number of steps, the total ROC value did not improve appreciably. Conclusions Although not ideal for screening patients who may have peripheral neuropathy, counting the number of steps during TW is a quick and useful clinical test. TW is most sensitive to peripheral neuropathy patients when they are tested with eyes closed. PMID:24096950

  9. Diabetic peripheral neuropathy may not be as its name suggests: evidence from magnetic resonance imaging.

    PubMed

    Tesfaye, Solomon; Selvarajah, Dinesh; Gandhi, Rajiv; Greig, Marni; Shillo, Pallai; Fang, Fang; Wilkinson, Iain D

    2016-02-01

    Diabetic peripheral neuropathy (DPN) affects up to 50% of patients with diabetes and is a major cause of morbidity and increased mortality. Its clinical manifestations include distressing painful neuropathic symptoms and insensitivity to trauma that result in foot ulcerations and amputations. Several recent studies have implicated poor glycemic control, duration of diabetes, hyperlipidemia (particularly hypertryglyceridaemia), elevated albumin excretion rates, and obesity as risk factors for the development of DPN. However, similar data are not available for painful DPN. Moreover, although there is now strong evidence for the importance of peripheral nerve microvascular disease in the pathogenesis of DPN, peripheral structural biomarkers of painful DPN are lacking. However, there is now emerging evidence for the involvement of the central nervous system in both painful and painless DPN afforded by magnetic resonance imaging. This review will focus on this emerging evidence for central changes in DPN, hitherto considered a peripheral nerve disease only. PMID:26785159

  10. Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy

    SciTech Connect

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

    1994-09-01

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

  11. Insulin influenced expression of myelin proteins in diabetic peripheral neuropathy.

    PubMed

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

    2016-08-26

    Diabetic peripheral neuropathy (DPN) is one of the downstream complications of diabetes. This complication is caused by the deficiency of insulin action and subsequent hyperglycemia, but the details of their pathogenesis remain unclear. Hence, it is of critical importance to understand how such hormonal variation affects the expression of myelin proteins such as myelin basic protein (MBP) and myelin associated glycoprotein (MAG) in the peripheral nerve. An earlier report from our lab has demonstrated the expression of insulin receptors (IR) in Schwann cells (SCs) of sciatic nerve. To assess the neurotrophic role of insulin in diabetic neuropathy, we studied the expression of these myelin proteins under control, DPN and insulin treated DPN subjects at developmental stages. Further, the expression of these myelin proteins was correlated with the expression of insulin receptor. Expression of myelin proteins was significantly reduced in the diabetic model compared to normal, and upregulated in insulin treated diabetic rats. Similarly, an in vitro study was also carried out in SCs grown at high glucose and insulin treated conditions. The expression pattern of myelin proteins in SCs was comparable to that of in vivo samples. In addition, quantitative study of myelin genes by real time PCR has also showed the significant expression pattern change in the insulin treated and non-treated DPN subjects. Taken together, these results corroborate the critical importance of insulin as a neurotrophic factor in demyelinized neurons in diabetic neuropathy. PMID:27373589

  12. Motor neuropathy in porphobilinogen deaminase–deficient mice imitates the peripheral neuropathy of human acute porphyria

    PubMed Central

    Lindberg, Raija L.P.; Martini, Rudolf; Baumgartner, Matthias; Erne, Beat; Borg, Jacques; Zielasek, Jürgen; Ricker, Kenneth; Steck, Andreas; Toyka, Klaus V.; Meyer, Urs A.

    1999-01-01

    Acute porphyrias are inherited disorders caused by partial deficiency of specific heme biosynthesis enzymes. Clinically, porphyrias are manifested by a neuropsychiatric syndrome that includes peripheral neuropathy. Although much is known about the porphyrias’ enzyme defects and their biochemical consequences, the cause of the neurological manifestations remains unresolved. We have studied porphyric neuropathy in mice with a partial deficiency of porphobilinogen deaminase (PBGD). PBGD-deficient mice (PBGD–/–) imitate acute porphyria through massive induction of hepatic δ-aminolevulinic acid synthase by drugs such as phenobarbital. Here we show that PBGD–/– mice develop impairment of motor coordination and muscle weakness. Histologically femoral nerves of PBGD–/– mice exhibit a marked decrease in large-caliber (>8 μm) axons and ultrastructural changes consistent with primary motor axon degeneration, secondary Schwann cell reactions, and axonal regeneration. These findings resemble those found in studies of affected nerves of patients with acute porphyria and thus provide strong evidence that PBGD deficiency causes degeneration of motor axons without signs of primary demyelination, thereby resolving a long-standing controversy. Interestingly, the neuropathy in PBGD–/– mice developed chronically and progressively and in the presence of normal or only slightly (twofold) increased plasma and urinary levels of the putative neurotoxic heme precursor δ-aminolevulinic acid. These data suggest that heme deficiency and consequent dysfunction of hemeproteins can cause porphyric neuropathy. PMID:10207164

  13. Schwann cells as a therapeutic target for peripheral neuropathies

    PubMed Central

    Lehmann, Helmar C.; Höke, Ahmet

    2014-01-01

    Schwann cells, the myelin forming cells in the peripheral nervous system, play a key role in the pathology of various inflammatory, metabolic and hereditary polyneuropathies. Advances in identifying growth factors and signaling molecules that are expressed by Schwann cells have paved the way to development of new treatment strategies that are aimed to improve the protective and regenerative properties of Schwann cells in peripheral nerve disorders. These include the exogenous application of growth factors and neurohormones, which have been advanced into clinical trials in humans and transplantation paradigms that have been moved into late stage preclinical models. In this review we will discuss the latest developments in these therapeutic approaches with special regard to peripheral nerve disorders, in which the progress in basic research have already been translated into clinical trials including HIV-associated distal sensory polyneuropathy and diabetic neuropathy. PMID:20874704

  14. Charcot-Marie-Tooth disease and related peripheral neuropathies.

    PubMed

    De Jonghe, P; Timmerman, V; Nelis, E; Martin, J J; Van Broeckhoven, C

    1997-01-01

    Soon after the description of Charcot-Marie-Tooth disease (CMT) in 1886, it became apparent that this syndrome is clinically and genetically heterogeneous. Neuropathological and electrophysiological studies have further dissected this syndrome into distinct categories that are now classified in a complex nosology of the inherited peripheral neuropathies. The recent advent of molecular genetics has dramatically increased our understanding of the underlying disease mechanisms. Genetic linkage studies have identified at least 17 genetic loci for different types of inherited neuropathies although most genes involved still remain to be found. The application of molecular genetics has already had an important impact on clinical practice and genetic counselling. Three genes responsible for hereditary motor and sensory neuropathy type I (HMSNI) or CMT1 have been identified: peripheral myelin protein 22 (PMP22) and myelin protein zero (MPZ) for the autosomal dominant form and connexin 32 (Cx32) for the X-linked dominant variant. The PMP22 gene is also involved in the majority of families with hereditary neuropathy with liability to pressure palsies (HNPP). The observation of a 1.5 Mb tandem duplication in chromosome 17p11.2, containing the PMP22 gene, in CMT1 and the reciprocal deletion in the same region in HNPP has provided a novel disease paradigm for autosomal dominant disorders, i.e. the gene dosage mechanism. The study of phenotype-genotype correlations in transgenic animal models for PMP22, MPZ and Cx32 mutations will help elucidate the underlying disease mechanisms and will provide a basis for gene therapy and/or other therapeutic approaches such as treatment with neurotrophic growth factors. PMID:10975746

  15. Pain modality and spinal glia expression by streptozotocin induced diabetic peripheral neuropathy in rats

    PubMed Central

    Kim, Sok Ho; Kwon, Jung Kee

    2012-01-01

    Pain symptoms are a common complication of diabetic peripheral neuropathy or an inflammatory condition. In the most experiments, only one or two evident pain modalities are observed at diabetic peripheral neuropathy according to experimental conditions. Following diabetic peripheral neuropathy or inflammation, spinal glial activation may be considered as an important mediator in the development of pain. For this reason, the present study was aimed to address the induction of pain modalities and spinal glial expression after streptozotocin injection as compared with that of zymosan inflammation in the rat. Evaluation of pain behavior by either thermal or mechanical stimuli was performed at 3 weeks or 5 hours after either intravenous streptozotocin or zymosan. Degrees of pain were divided into 4 groups: severe, moderate, mild, and non-pain induction. On the mechanical allodynia test, zymosan evoked predominantly a severe type of pain, whereas streptozotocin induced a weak degree of pain (severe+moderate: 57.1%). Although zymosan did not evoke cold allodynia, streptozotocin evoked stronger pain behavior, compared with zymosan (severe+moderate: 50.0%). On the other hand, the high incidence of thermal hyperalgesia (severe+moderate: 90.0%) and mechanical hyperalgesia (severe+moderate: 85.7%) by streptozotocin was observed, as similar to that of zymosan. In the spinal cord, the increase of microglia and astrocyte was evident by streptozotocin, only microglia was activated by zymosan. Therefore, it is recommended that the selection of mechanical and thermal hyperalgesia is suitable for the evaluation of streptozotocin induced diabetic peripheral neuropathy. Moreover, spinal glial activation may be considered an important factor. PMID:22787487

  16. Disease associated with exposure to certain herbicide agents: peripheral neuropathy.

    PubMed

    2013-09-01

    The Department of Veterans Affairs (VA) adopts as a final rule its proposal to amend its adjudication regulations by clarifying and expanding the terminology regarding presumptive service connection for acute and subacute peripheral neuropathy associated with exposure to certain herbicide agents. This amendment implements a decision by the Secretary of Veterans Affairs based on findings from the National Academy of Sciences (NAS) Institute of Medicine report, Veterans and Agent Orange: Update 2010. It also amends VA's regulation governing retroactive awards for certain diseases associated with herbicide exposure as required by court orders in the class action litigation of Nehmer v. U.S. Department of Veterans Affairs. PMID:24040683

  17. Peripheral neuropathy after hair dye exposure: a case report.

    PubMed

    Deeb, Wissam; Cachia, David; Quinn, Colin; Salameh, Johnny

    2014-06-01

    We present a case of length-dependent sensory axonal polyneuropathy due to lead exposure from a cosmetic product. Serial follow-ups showed a direct relationship between the lead level, clinical symptoms, and the polyneuropathy. Our patient had a relatively short-term exposure to lead after misusing a hair dye on his beard. Nerve conduction studies showed a predominantly axonal sensory neuropathy that correlated with lead blood levels and reached 3 times the upper limit of normal. The patient had an unexpected sensory predominant neuropathy. He had a full recovery after stopping the lead-containing product. Blood lead levels were noted to be below previously reported toxic levels. No other systemic signs of lead toxicity were noted. This could be related to the mucosal route of absorption inducing a reversible injury at lower than previously reported lead levels and after a shorter duration of exposure. PMID:24872215

  18. The armadillo as a model for peripheral neuropathy in leprosy.

    PubMed

    Truman, Richard W; Ebenezer, Gigi J; Pena, Maria T; Sharma, Rahul; Balamayooran, Gayathriy; Gillingwater, Thomas H; Scollard, David M; McArthur, Justin C; Rambukkana, Anura

    2014-01-01

    Leprosy (also known as Hansen's Disease) is a chronic infectious disease caused by Mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. Other than humans, nine-banded armadillos (Dasypus novemcinctus) are the only natural hosts of M. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium. Infection in the armadillo closely recapitulates many of the structural, physiological, and functional aspects of leprosy seen in humans. Armadillos can be useful models of leprosy for basic scientific investigations into the pathogenesis of leprosy neuropathy and its associated myopathies, as well as for translational research studies in piloting new diagnostic methods or therapeutic interventions. Practical and ethical constraints often limit investigation into human neuropathies, but armadillos are an abundant source of leprotic neurologic fibers. Studies with these animals may provide new insights into the mechanisms involved in leprosy that also might benefit the understanding of other demyelinating neuropathies. Although there is only a limited supply of armadillo-specific reagents, the armadillo whole genomic sequence has been completed, and gene expression studies can be employed. Clinical procedures, such as electrophysiological nerve conduction testing, provide a functional assessment of armadillo nerves. A variety of standard histopathological and immunopathological procedures including Epidermal Nerve Fiber Density (ENFD) analysis, Schwann Cell Density, and analysis for other conserved cellular markers can be used effectively with armadillos and will be briefly reviewed in this text. PMID:24615444

  19. The Armadillo as a Model for Peripheral Neuropathy in Leprosy

    PubMed Central

    Truman, Richard W.; Ebenezer, Gigi J.; Pena, Maria T.; Sharma, Rahul; Balamayooran, Gayathriy; Gillingwater, Thomas H.; Scollard, David M.; McArthur, Justin C.; Rambukkana, Anura

    2014-01-01

    Leprosy (also known as Hansen's Disease) is a chronic infectious disease caused by Mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. Other than humans, nine-banded armadillos (Dasypus novemcinctus) are the only natural hosts of M. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium. Infection in the armadillo closely recapitulates many of the structural, physiological, and functional aspects of leprosy seen in humans. Armadillos can be useful models of leprosy for basic scientific investigations into the pathogenesis of leprosy neuropathy and its associated myopathies, as well as for translational research studies in piloting new diagnostic methods or therapeutic interventions. Practical and ethical constraints often limit investigation into human neuropathies, but armadillos are an abundant source of leprotic neurologic fibers. Studies with these animals may provide new insights into the mechanisms involved in leprosy that also might benefit the understanding of other demyelinating neuropathies. Although there is only a limited supply of armadillo-specific reagents, the armadillo whole genomic sequence has been completed, and gene expression studies can be employed. Clinical procedures, such as electrophysiological nerve conduction testing, provide a functional assessment of armadillo nerves. A variety of standard histopathological and immunopathological procedures including Epidermal Nerve Fiber Density (ENFD) analysis, Schwann Cell Density, and analysis for other conserved cellular markers can be used effectively with armadillos and will be briefly reviewed in this text. PMID:24615444

  20. Postural sway in diabetic peripheral neuropathy among Indian elderly

    PubMed Central

    Dixit, Snehil; Maiya, Arun; Shasthry, B.A.; Kumaran, D. Senthil; Guddattu, Vasudeva

    2015-01-01

    Background & objectives: Diabetic peripheral neuropathy (DPN) is a major complication of type 2 diabetes and have long term complications on the postural control of the affected population. The objectives of this study were to evaluate postural stability in patients with DPN and to examine correlation of Michigan Neuropathy Screening Instrument (MNSI) with duration of diabetes, age and postural stability measures. Methods: Participants were included if they had clinical neuropathy which was defined by MNSI. Sixty one patients gave their consent to participate in the study and were evaluated on posturography for postural stability measures in four conditions. Repeated measures of analysis of variance (RANOVA) was used to analyze the changes in postural stability measures in different conditions. Results: An increase in mean value of postural stability measures was observed for velocity moment 20.4±1.3, 24.3±2.2, 42.3±20.7, 59±43.03, mediolateral displacement 0.21±0.10, 0.22±0.18, 0.03±0.11, 0.34±0.18, and anteroposterior displacement 0.39 ± 0.09, 0.45±0.12, 0.47±0.13, 0.51±0.20 from EO to EC, EOF, and ECF, respectively. There was a significant difference (P<0.05) in participants with DPN, with greater sway amplitude on firm and foam surface in all the conditions. Moderate correlation of MNSI with age (r=0.43) and postural stability measures were also observed. Interpretation & conclusions: Evaluation of postural stability in Indian DPN population suggests balance impairments on either firm and foam surfaces, with greater likelihood of fall being on foam or deformable surfaces among elderly adults with neuropathy (CTRI/2011/07/001884). PMID:26831420

  1. Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

    PubMed Central

    Coriat, Romain; Alexandre, Jérôme; Nicco, Carole; Quinquis, Laurent; Benoit, Evelyne; Chéreau, Christiane; Lemaréchal, Hervé; Mir, Olivier; Borderie, Didier; Tréluyer, Jean-Marc; Weill, Bernard; Coste, Joel; Goldwasser, François; Batteux, Frédéric

    2013-01-01

    Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer. Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ≥2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir. Results. Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles, neurotoxicity was downgraded to grade ≥2 in 6 of 7 patients. Prior to enrollment, patients received an average of 880 ± 239 mg/m2 oxaliplatin. Patients treated with mangafodipir tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin. Serum AOPPs were lower in responders compared with those in nonresponders. Conclusion. Our study suggests that mangafodipir can prevent and/or relieve oxaliplatin-induced neuropathy in cancer patients. Trial registration. Clinicaltrials.gov NCT00727922. Funding. Université Paris Descartes, Ministère de la Recherche et de l’Enseignement Supérieur, and Assistance Publique-Hôpitaux de Paris. PMID:24355920

  2. Putting evidence into practice: evidence-based interventions for chemotherapy-induced peripheral neuropathy.

    PubMed

    Visovsky, Constance; Collins, Mary; Abbott, Linda; Aschenbrenner, Julie; Hart, Connie

    2007-12-01

    Chemotherapy-induced peripheral neuropathy (CIPN) continues to be a significant, debilitating symptom resulting from the administration of neurotoxic chemotherapy for the treatment of cancer. CIPN is an important consequence of cancer treatment because of its potential impact on physical functioning and quality of life. Oncology nurses play an important role in assessing, monitoring, and educating clients about CIPN. Despite investigations concerning pharmacologic and nonpharmacologic approaches to either preventing or minimizing the neurotoxicity resulting from certain chemotherapeutic agents, evidence to support the interventions is lacking. This article presents information concerning CIPN and summarizes the evidence for pharmacologic and nonpharmacologic approaches to the prevention and treatment of CIPN. PMID:18063548

  3. Chemotherapy-induced peripheral neuropathy - diagnosis, evolution and treatment.

    PubMed

    Iżycki, Dariusz; Niezgoda, Adam Andrzej; Kaźmierczak, Maciej; Piorunek, Tomasz; Iżycka, Natalia; Karaszewska, Bogusława; Nowak-Markwitz, Ewa

    2016-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent neurologic complications experienced by patients receiving antineoplastic drugs. Involvement of the peripheral nerves may have an important impact on daily activi-ties and lead to severe impairment of the patient's quality of life (QoL). It seems to be of crucial importance to make a correct and early diagnosis of polyneuropathy and, if possible, spare the patient unnecessary suffering or loss of function. In the preceding article we have presented epidemiology, grading and pathogenesis of the toxic CIPN. The purpose of this article is to review current knowledge of diagnostic techniques, prevention and management strategies in the context of CIPN. PMID:27504945

  4. The Role of Advanced Glycation Endproducts and Glyoxalase I in Diabetic Peripheral Sensory Neuropathy

    PubMed Central

    Jack, M.M.; Wright, D.E.

    2012-01-01

    Diabetic neuropathy is the most common and debilitating complication of diabetes mellitus with over half of all patients developing altered sensation as a result of damage to peripheral sensory neurons. Hyperglycemia results in altered nerve conduction velocities, loss of epidermal innervation, and the development of painful or painless signs and symptoms in the feet and hands. Current research has been unable to determine if a patient will develop insensate or painful neuropathy or be protected from peripheral nerve damage all together. One of the mechanisms that has been recognized to have a role in the pathogenesis of sensory neuron damage is the process of reactive dicarbonyls forming advanced glycation endproducts (AGEs) as a direct result of hyperglycemia. The glyoxalase system, composed of the enzymes glyoxalase I (GLO1) and glyoxalase II, is the main detoxification pathway involved in breaking down toxic reactive dicarbonyls before producing carbonyl stress and forming AGEs on proteins, lipids, or nucleic acids. This review discusses AGEs, GLO1, their role in diabetic neuropathy, and potential therapeutic targets of the AGE pathway. PMID:22500508

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

    PubMed Central

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

    2016-01-01

    [Purpose] The effects of vitamin D on the circulating levels of IL-17 and IL-13 were investigated in patients with diabetic peripheral neuropathy, patients with diabetes mellitus type 2 without neuropathy, and healthy controls. [Subjects and Methods] A single-blind controlled clinical study was performed, including70 type 2 diabetic patients with or without diabetic peripheral neuropathy and 33 healthy volunteer controls. The 25(OH)D levels were evaluated using ultra-performance liquid chromatography, and IL-17 and IL-13 levels were assessed using enzyme-linked immunosorbent assays. [Results] The 25(OH) vitamin D concentration was lower in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy and healthy controls. Similarly, 25(OH)D levels were lower in diabetes mellitus patients than healthy controls. IL-17 and IL-13 levels were higher in diabetes mellitus patients than in controls. Additionally, IL-13 levels were higher in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy. These differences were statistically significant. There was a significant positive correlation between 25(OH)D and IL-13,and a negative correlation between 25(OH)D andIL-17 in the diabetic and diabetic neuropathy groups. [Conclusion] Vitamin D is a potential modifiable risk factor for diabetic peripheral neuropathy and may regulate inflammatory mediators, e.g., IL-17 and IL-13. PMID:27512288

  6. Ultrasound assessment of selected peripheral nerves pathologies. Part II: Entrapment neuropathies of the lower limb

    PubMed Central

    Sudoł-Szopińska, Iwona

    2012-01-01

    Similarly to entrapment neuropathies of upper extremities, the ultrasound constitutes a valuable supplementation of diagnostic examinations performed in patients with suspicions of nerve entrapment syndromes of the lower limb. For many years, it was claimed that such pathologies were rare. This probably resulted from the lack of proper diagnostic tools (including high frequency ultrasound transducers) as well as the lack of sufficient knowledge in this area. In relation to the above, the symptoms of compression neuropathies were frequently interpreted as a manifestation of pathologies of the lumbar part of the spine or a other orthopedic disease (degenerative or overuse one). Consequently, many patients were treated ineffectively for many months and even, years which led to irreparable neurological changes and changes in the motor organ. Apart from a clinical examination, the diagnostics of entrapment neuropathies of lower limb is currently based on imaging tests (ultrasound, magnetic resonance) as well as functional assessments (electromyography). Magnetic resonance imaging is characterized by a relatively low resolution (as compared to ultrasound) which results in limited possibilities of morphological evaluation of the visualized pathology. Electromyography allows for the assessment of nerve function, but does not precisely determine the type and degree of change. This article presents examples of the most common entrapment neuropathies of the lower limb concerning the following nerves: sciatic, femoral, lateral femoral cutaneous, obturator, fibular and its branches, tibial and its branches as well as sural. The pathomorphological basis of the neuropathies as well as corresponding ultrasound images are presented in this paper. Attention has been drawn to echogenicity, degree of vascularization and bundle presentation of the trunk of a pathological peripheral nerve. PMID:26673938

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

    SciTech Connect

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

    1991-07-01

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

  8. Increased lipid droplet accumulation associated with a peripheral sensory neuropathy.

    PubMed

    Marshall, Lee L; Stimpson, Scott E; Hyland, Ryan; Coorssen, Jens R; Myers, Simon J

    2014-04-01

    Hereditary sensory neuropathy type 1 (HSN-1) is an autosomal dominant neurodegenerative disease caused by missense mutations in the SPTLC1 gene. The SPTLC1 protein is part of the SPT enzyme which is a ubiquitously expressed, critical and thus highly regulated endoplasmic reticulum bound membrane enzyme that maintains sphingolipid concentrations and thus contributes to lipid metabolism, signalling, and membrane structural functions. Lipid droplets are dynamic organelles containing sphingolipids and membrane bound proteins surrounding a core of neutral lipids, and thus mediate the intracellular transport of these specific molecules. Current literature suggests that there are increased numbers of lipid droplets and alterations of lipid metabolism in a variety of other autosomal dominant neurodegenerative diseases, including Alzheimer's and Parkinson's disease. This study establishes for the first time, a significant increase in the presence of lipid droplets in HSN-1 patient-derived lymphoblasts, indicating a potential connection between lipid droplets and the pathomechanism of HSN-1. However, the expression of adipophilin (ADFP), which has been implicated in the regulation of lipid metabolism, was not altered in lipid droplets from the HSN-1 patient-derived lymphoblasts. This appears to be the first report of increased lipid body accumulation in a peripheral neuropathy, suggesting a fundamental molecular linkage between a number of neurodegenerative diseases. PMID:24711860

  9. Peripheral neuropathy and parkinsonism: a large clinical and pathogenic spectrum.

    PubMed

    Vital, Anne; Lepreux, Sebastien; Vital, Claude

    2014-12-01

    Peripheral neuropathy (PN) has been reported in idiopathic and hereditary forms of parkinsonism, but the pathogenic mechanisms are unclear and likely heterogeneous. Levodopa-induced vitamin B12 deficiency has been discussed as a causal factor of PN in idiopathic Parkinson's disease, but peripheral nervous system involvement might also be a consequence of the underlying neurodegenerative process. Occurrence of PN with parkinsonism has been associated with a panel of mitochondrial cytopathies, more frequently related to a nuclear gene defect and mainly polymerase gamma (POLG1) gene. Parkin (PARK2) gene mutations are responsible for juvenile parkinsonism, and possible peripheral nervous system involvement has been reported. Rarely, an association of parkinsonism with PN may be encountered in other neurodegenerative diseases such as fragile X-associated tremor and ataxia syndrome related to premutation CGG repeat expansion in the fragile X mental retardation (FMR1) gene, Machado-Joseph disease related to an abnormal CAG repeat expansion in ataxin-3 (ATXN3) gene, Kufor-Rakeb syndrome caused by mutations in ATP13A2 gene, or in hereditary systemic disorders such as Gaucher disease due to mutations in the β-glucocerebrosidase (GBA) gene and Chediak-Higashi syndrome due to LYST gene mutations. This article reviews conditions in which PN may coexist with parkinsonism. PMID:25582874

  10. Targeting the Diabetic Chaperome to Improve Peripheral Neuropathy.

    PubMed

    Dobrowsky, Rick T

    2016-08-01

    The chaperome constitutes a broad family of molecular chaperones and co-chaperones that facilitate the folding, refolding, and degradation of the proteome. Heat shock protein 90 (Hsp90) promotes the folding of numerous oncoproteins to aid survival of malignant phenotypes, and small molecule inhibitors of the Hsp90 chaperone complex offer a viable approach to treat certain cancers. One therapeutic attribute of this approach is the selectivity of these molecules to target high affinity oncogenic Hsp90 complexes present in tumor cells, which are absent in nontransformed cells. This selectivity has given rise to the idea that disease may contribute to forming a stress chaperome that is functionally distinct in its ability to interact with small molecule Hsp90 modulators. Consistent with this premise, modulating Hsp90 improves clinically relevant endpoints of diabetic peripheral neuropathy but has little impact in nondiabetic nerve. The concept of targeting the "diabetic chaperome" to treat diabetes and its complications is discussed. PMID:27318486

  11. Effects of Dioscoreae Rhizoma (SanYak) on Peripheral Neuropathy and its Safety

    PubMed Central

    Kim, Min-jung; Sung, Hyunkyung; Hong, Kwon-eui

    2013-01-01

    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. PMID:25780670

  12. Hydatid cyst of biceps brachii associated with peripheral neuropathy

    PubMed Central

    Tuna, Serkan; Duymus, Tahir Mutlu; Yanik, Hakan Serhat; Durakbasa, Mehmet Oguz; Mutlu, Serhat; Erdem, Sevki

    2015-01-01

    Introduction Hydatidosis represents the most significant parasitic disorder in the Mediterranean countries and leads to major problems through unfavorable effects on the public health and national economy. Localization of the primary cyst hydatid infection in the extremity is rare and biceps brachii localization is also rarely reported in the literature. Presentation of case A 43-year-old woman, who presented with the complaints of mass and pain in the left arm and numbness of the hand. Laboratory investigations, X-ray and magnetic resonance (MRI) findings revealed hydatid cyst of the biceps brachi muscle. The mass was totally excised and the diagnosis was confirmed by the macroscopic images of the mass and the pathologic results. After the surgery, the patient had an improvement in the nerve compression findings including numbness of the hand and the upper extremity and pain. Discussion Localization of a primary cyst hydatid infection in the upper extremity is rare and there are no reports of peripheral neuropathy secondary to mass effect. Even if the pre-surgical electromyelography performed for the nerve conduction study reveals a normal result, the potential for the hydatid cysts to cause nerve compression should be taken into consideration in such patients. Conclusion Cases of concomitant neurologic findings and complaints secondary to peripheral nerve compression are very rare. The clinical findings should not be ruled out even if the EMG result is negative. PMID:25682195

  13. Spectrum of peripheral neuropathies associated with surgical interventions; A neurophysiological assessment

    PubMed Central

    2010-01-01

    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. PMID:20398427

  14. The Prevalence of Diabetic Peripheral Neuropathy and Related Factors

    PubMed Central

    Tabatabaei-Malazy, O; Mohajeri-Tehrani, MR; Madani, SP; Heshmat, R; Larijani, B

    2011-01-01

    Background Diabetic peripheral neuropathy (DPN) accounts for 80% of diabetic foot ulceration; therefore neurologic examination plays a critical role in screening at risk patients. Our objective was assessment the prevalence of DPN and related factors based on clinical findings. Methods: This cross-sectional study was conducted on 124 diabetics who were randomly recruited from Diabetes Clinic of Dr. Shariati University Hospital (Tehran/Iran) in 2004. After gathering demographic data and blood sampling for fasting blood sugar (FBS), the questionnaires United Kingdom (UK), Michigan, Diabetic Neuropathy Score (DNS), and 10-g monofilament testing were administered. Analysis tests were chi-square, pearson correlation and logistic regression. Results: The patient’s age ranged 17–75 years; with 44% male. Ninety one percent suffered from type two diabetes and the mean duration of diabetes was 10 years. The mean FBS level was 181.5 mg/dl. While the prevalence of DPN based on Michigan, DNS, and monofilament testing was about 32–38%, some 54% were diagnosed by UK test. Tingling in the lower extremity was the most frequent complaint (42%). The strongest linear correlation was reported between Michigan and DNS (r= 0.7), and then between monofilament test and DNS (r= 0.6). The age > 50 years, length of diabetes > 10 years, and FBS >200 mg/dl were the main risk factors for DPN based on DNS. Conclusion: It seems that the combination of Michigan and monofilament test can provide an accurate screening tool for detecting DPN. In addition, tight glucose control, regular assessment of the lower extremity, and to educate diabetics is urged in elderly diabetics, longer duration of diabetes, and those with high FBS. PMID:23113086

  15. Antibodies to gliomedin cause peripheral demyelinating neuropathy and the dismantling of the nodes of Ranvier.

    PubMed

    Devaux, Jérôme J

    2012-10-01

    Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are conditions that affect peripheral nerves. The mechanisms that underlie demyelination in these neuropathies are unknown. Recently, we demonstrated that the node of Ranvier is the primary site of the immune attack in patients with GBS and CIDP. In particular, GBS patients have antibodies against gliomedin and neurofascin, two adhesion molecules that play a crucial role in the formation of nodes of Ranvier. We demonstrate that immunity toward gliomedin, but not neurofascin, induced a progressive neuropathy in Lewis rats characterized by conduction defects and demyelination in spinal nerves. The clinical symptoms closely followed the titers of anti-gliomedin IgG and were associated with an important deposition of IgG at nodes. Furthermore, passive transfer of antigliomedin IgG induced a severe demyelinating condition and conduction loss. In both active and passive models, the immune attack at nodes occasioned the loss of the nodal clusters for gliomedin, neurofascin-186, and voltage-gated sodium channels. These results indicate that primary immune reaction against gliomedin, a peripheral nervous system adhesion molecule, can be responsible for the initiation or progression of the demyelinating form of GBS. Furthermore, these autoantibodies affect saltatory propagation by dismantling nodal organization and sodium channel clusters. Antibodies reactive against nodal adhesion molecules thus likely participate in the pathologic process of GBS and CIDP. PMID:22885108

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

    PubMed

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

    2014-11-01

    Peripheral neuropathy caused by cytotoxic chemotherapy, especially platins and taxanes, is a widespread problem among cancer survivors that is likely to continue to expand in the future. However, little work to date has focused on understanding this challenge. The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight into the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing before and then prior to each cycle of oxaliplatin. These data were compared with those from 47 age- and sex-matched healthy volunteers. Patients showed significant subclinical deficits in sensory function before any therapy compared with healthy volunteers, and they became more pronounced in patients who received chemotherapy. Sensory modalities that involved large Aβ myelinated fibers and unmyelinated C fibers were most affected by chemotherapy, whereas sensory modalities conveyed by thinly myelinated Aδ fibers were less sensitive to chemotherapy. Patients with baseline sensory deficits went on to develop more symptom complaints during chemotherapy than those who had no baseline deficit. Patients who were tested again 6 to 12 months after chemotherapy presented with the most numbness and pain and also the most pronounced sensory deficits. Our results illuminate a mechanistic connection between the pattern of effects on sensory function and the nerve fiber types that appear to be most vulnerable to chemotherapy-induced toxicity, with implications for how to focus future work to ameloirate risks of peripheral neuropathy. PMID:25183707

  17. Pedal pathology potentiated by personal pedicure procedures in the presence of painless peripheral neuropathy.

    PubMed

    Zhubrak, Michelle S; Fisher, Timothy K; Armstrong, David G

    2013-01-01

    Although the literature is replete with recommendations for people with diabetes-particularly those with neuropathy, ischemia, or both-to avoid caring for corns and calluses on their own feet, there are virtually no reports of damage associated with this care. The purpose of this article is to report on the potential perils of personal pedicures in the presence of peripheral neuropathy by using a case-based example. In this article, we report on the inappropriate use of a Ped Egg personal pedicure device that led to limb-threatening lesions in a gentleman with diabetic peripheral sensory neuropathy. PMID:24072378

  18. Neuroprotective effects of folic acid on experimental diabetic peripheral neuropathy.

    PubMed

    Yilmaz, Mustafa; Aktug, Huseyin; Oltulu, Fatih; Erbas, Oytun

    2016-05-01

    Diabetic peripheral neuropathy (DPN) is widely considered as a degenerative complication of diabetic patients. The clinical effectiveness of folic acid (FA) on DPN is uncertain. The objective of the present study was to determine the effect of FA in DPN using electromyography (EMG), histopathological examination, immunohistochemistry, inclined plane test, and malondialdehyde (MDA) levels as a marker for lipid peroxidation in experimental diabetic rats. A total of 21 Sprague Dawley rats were randomly divided into 3 groups: control group, diabetes group, and FA-treated group. In EMG, compound muscle action potential (CMAP) amplitude in the sciatic nerve was lower in the diabetes group compared with the control group. CMAP amplitude in the sciatic nerve was higher in the FA-treated group when compared with the diabetes group. Distal latency and CMAP duration in the sciatic nerve were lower in the FA-treated group when compared with the diabetes group. In histopathological examination of the sciatic nerve, peripheral fibrosis was present in the diabetic group; the fibrosis was lower in the FA-treated group. In comparison with the diabetes group, the expression of nerve growth factor (NGF) was higher in the FA-treated group. The scores for the inclined plane test were lower in the diabetes group and higher in the FA-treated group than the control group. The MDA levels were significantly lower in the FA-treated group when compared with the diabetes group.The study suggests that FA can protect diabetic rats against DPN and that the underlying mechanism for this may be related to improvement of the expression of NGF and lower MDA levels. PMID:24311627

  19. Neurotoxic catecholamine metabolite in nociceptors contributes to painful peripheral neuropathy.

    PubMed

    Dina, Olayinka A; Khasar, Sachia G; Alessandri-Haber, Nicole; Bogen, Oliver; Chen, Xiaojie; Green, Paul G; Reichling, David B; Messing, Robert O; Levine, Jon D

    2008-09-01

    The neurotoxic effects of catecholamine metabolites have been implicated in neurodegenerative diseases. As some sensory neurons express tyrosine hydroxylase and monoamine oxidase (MAO), we investigated the potential contribution of catecholamine metabolites to neuropathic pain in a model of alcoholic neuropathy. The presence of catecholamines in sensory neurons is supported by capsaicin-stimulated epinephrine release, an effect enhanced in ethanol-fed rats. mRNA for enzymes in dorsal root ganglia involved in catecholamine uptake and metabolism, dopamine beta-hydroxylase and MAO-A, were decreased by neonatal administration of capsaicin. Ethanol-induced hyperalgesia was attenuated by systemic and local peripheral administration of inhibitors of MAO-A, reduction of norepinephrine transporter (NET) in sensory neurons and a NET inhibitor. Finally, intradermal injection of 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), a neurotoxic MAO-A catecholamine metabolite, produced robust mechanical hyperalgesia. These observations suggest that catecholamines in nociceptors are metabolized to neurotoxic products by MAO-A, which can cause neuronal dysfunction underlying neuropathic pain. PMID:18783367

  20. A case of refractory IgG4-related peripheral neuropathy with severe axonal damage.

    PubMed

    Suzuki, Yu; Shiraishi, Makoto; Yamada, Koji; Doi, Masatomo; Kato, Masayuki; Hasegawa, Yasuhiro

    2016-05-31

    A 78-year-old man presented complaining of tingling and pain. Neurological examination revealed dysesthesia and hypothermesthesia below both knees and areflexia in the lower extremities. Laboratory data revealed elevated serum levels of immunoglobulin IgG4 and para-aortic, and mesenteric lymphadenopathy was evident on plain computed tomography of the abdomen. Microscopic findings of a bone marrow biopsy specimen showed occlusion of blood vessels with IgG4-positive plasma cells. IgG4-related disease was diagnosed because the bone marrow biopsy exhibited > 10 IgG4-positive plasma cells per high-power field. Treatment was initiated with prednisolone starting at 30 mg/day, but no improvement in neurological symptoms was achieved. Sural nerve biopsy demonstrated obstructive thromboangiitis with severe loss of myelin and axons. Further investigations are needed to elucidate the relationship between obstructive thromboangiitis and steroid-resistant IgG4-related peripheral neuropathy. PMID:27098901

  1. Biologic Basis of Nerve Decompression Surgery for Focal Entrapments in Diabetic Peripheral Neuropathy.

    PubMed

    Sessions, John; Nickerson, D Scott

    2014-02-27

    The most recent (2011) National Diabetes Fact Sheet states the combined diagnosed and undiagnosed number of diabetes cases in the United States is approaching 25 million, and another 79 million are prediabetic. Of the diabetes patients, 60-70% suffer from mild to severe neuropathy. This combined loss of sensory and motor control in diabetic limbs is usually considered an irreversible, progressive process. Patients suffering from these losses are at a significantly higher risk for development of foot ulceration, frequently leading to infection and partial or major limb amputation. However, a review of focal nerve entrapment surgical decompression literature suggests that several diabetic sensorimotor polyneuropathy (DSPN) symptoms and complications are potentially partially reversible or preventable. Decompression surgery represents a paradigm shift in treatment protocols because it both relieves pain and restores protective sensation, while providing significant protection against a cascade of serious foot complications. This review surveys current research regarding the biological basis for diabetic focal entrapment neuropathy. Metabolic dysfunction related to aldose reductase, oxidative stress, and advanced glycation end products are considered and correlated to peripheral nerve enlargement and entrapment. In addition, observational studies correlated to that biological basis are presented as well as surgical outcomes illustrating the effect of decompression on DSPN symptomatic relief, nerve function, and protection against complications. PMID:24876595

  2. The Homology Model of PMP22 Suggests Mutations Resulting in Peripheral Neuropathy Disrupt Transmembrane Helix Packing

    PubMed Central

    2015-01-01

    Peripheral myelin protein 22 (PMP22) is a tetraspan membrane protein strongly expressed in myelinating Schwann cells of the peripheral nervous system. Myriad missense mutations in PMP22 result in varying degrees of peripheral neuropathy. We used Rosetta 3.5 to generate a homology model of PMP22 based on the recently published crystal structure of claudin-15. The model suggests that several mutations known to result in neuropathy act by disrupting transmembrane helix packing interactions. Our model also supports suggestions from previous studies that the first transmembrane helix is not tightly associated with the rest of the helical bundle. PMID:25243937

  3. Involvement of microglial CD40 in murine retrovirus-induced peripheral neuropathy.

    PubMed

    Cao, Ling; Butler, M Brady

    2013-08-15

    B6 mice infected with LP-BM5 develop severe immunodeficiency (termed murine acquired immunodeficiency syndrome (MAIDS)) and peripheral neuropathy. To determine whether microglial CD40 is involved in LP-BM5-induced peripheral neuropathy, B6-CD40 knockout (KO) mice and B6-CD40 KO mice adoptively transferred either total leukocytes or B cells were examined for behavioral sensitivity, tissue viral loads, cytokine responses, and the development of MAIDS. All three CD40 KO groups developed MAIDS, the severity of which was correlated with peripheral cytokine responses. CD40 KO mice displayed significantly reduced mechanical hypersensitivity post-infection compared to wild-type mice regardless of cell transfer. These findings support microglial CD40 involvement in LP-BM5-induced peripheral neuropathy. PMID:23726765

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

    PubMed Central

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

    2014-01-01

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

  5. Traumatic digital amputations of the foot inflicted by pet cat upon individual with diabetic peripheral neuropathy.

    PubMed

    Hoffman, William; Donovan, Kenneth

    2013-01-01

    Diabetic peripheral neuropathy (DPN) is a common cause of many lower-extremity complications. This case study illustrates the potential perils of pet ownership associated with diabetes and neuropathy. The case describes an incident resulting in traumatic digital amputations inflicted by a patient's pet feline while she was sleeping. In presenting this case, the potential risks of pet ownership for patients with DPN are discussed along with a review of the relevant literature. PMID:24072375

  6. Tadalafil Promotes the Recovery of Peripheral Neuropathy in Type II Diabetic Mice

    PubMed Central

    Wang, Lei; Chopp, Michael; Szalad, Alexandra; Lu, XueRong; Jia, LongFei; Lu, Mei; Zhang, Rui Lan; Zhang, Zheng Gang

    2016-01-01

    We previously demonstrated that treatment of diabetic peripheral neuropathy with the short (4 hours) half-life phosphodiesterase 5 (PDE5) inhibitor, sildenafil, improved functional outcome in diabetic db/db mice. To further examine the effect of PDE5 inhibition on diabetic peripheral neuropathy, we investigated the effect of another potent PDE5 inhibitor, tadalafil, on diabetic peripheral neuropathy. Tadalafil is pharmacokinetically distinct from sildenafil and has a longer half-life (17+hours) than sildenafil. Diabetic mice (BKS.Cg-m+/+Leprdb/J, db/db) at age 20 weeks were treated with tadalafil every 48 hours for 8 consecutive weeks. Compared with diabetic mice treated with saline, tadalafil treatment significantly improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal sensitivity. Tadalafil treatment also markedly increased local blood flow and the density of FITC-dextran perfused vessels in the sciatic nerve concomitantly with increased intraepidermal nerve fiber density. Moreover, tadalafil reversed the diabetes-induced reductions of axon diameter and myelin thickness and reversed the diabetes-induced increased g-ratio in the sciatic nerve. Furthermore, tadalafil enhanced diabetes-reduced nerve growth factor (NGF) and platelet-derived growth factor-C (PDGF-C) protein levels in diabetic sciatic nerve tissue. The present study demonstrates that tadalafil increases regional blood flow in the sciatic nerve tissue, which may contribute to the improvement of peripheral nerve function and the amelioration of diabetic peripheral neuropathy. PMID:27438594

  7. What Are the Signs and Symptoms of Peripheral Arterial Disease?

    MedlinePlus

    ... from the NHLBI on Twitter. What Are the Signs and Symptoms of Peripheral Artery Disease? Many people ... flow, so the symptoms will go away. Other Signs and Symptoms Other signs and symptoms of P. ...

  8. Peripheral sensory neuropathy is associated with altered postocclusive reactive hyperemia in the diabetic foot

    PubMed Central

    Barwick, Alex L; Tessier, John W; Janse de Jonge, Xanne; Ivers, James R; Chuter, Vivienne H

    2016-01-01

    Objective This study examined whether the presence of peripheral sensory neuropathy or cardiac autonomic deficits is associated with postocclusive reactive hyperemia (reflective of microvascular function) in the diabetic foot. Research design and methods 99 participants with type 2 diabetes were recruited into this cross-sectional study. The presence of peripheral sensory neuropathy was determined with standard clinical tests and cardiac autonomic function was assessed with heart rate variation testing. Postocclusive reactive hyperemia was measured with laser Doppler in the hallux. Multiple hierarchical regression was performed to examine relationships between neuropathy and the peak perfusion following occlusion and the time to reach this peak. Results Peripheral sensory neuropathy predicted 22% of the variance in time to peak following occlusion (p<0.05), being associated with a slower time to peak but was not associated with the magnitude of the peak. Heart rate variation was not associated with the postocclusive reactive hyperemia response. Conclusions This study found an association between the presence of peripheral sensory neuropathy in people with diabetes and altered microvascular reactivity in the lower limb. PMID:27486520

  9. Diabetic Neuropathy

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Diabetic Neuropathy Information Page Table of Contents (click to jump ... Organizations Additional resources from MedlinePlus What is Diabetic Neuropathy? Diabetic neuropathy is a peripheral nerve disorder caused ...

  10. [Old or new medicine? Vitamin B12 and peripheral nerve neuropathy].

    PubMed

    Tanaka, Hiroyuki

    2013-09-01

    Methylcobalamin is a vitamin B12 analog that is necessary for nervous system maintenance. Although methylcobalamin has some positive effects on peripheral nervous system disorders, the mechanism through which it affects neurons are not entirely known. Recent studies have revealed its intracellular signaling pathway and some of its molecular actions on neurons. In this article, I review interactions between methylcobalamin and neurons that have been revealed through in vitro studies, in vivo studies, and clinical use. Methylcobalamin participates in nervous system maintenance through several mechanisms. Methylcobalamin is an active form of vitamin B12, and a coenzyme of methionine synthase, which is required for DNA and protein methylation. In addition, methylcobalamin facilitates neurite outgrowth and inhibits neural apoptosis through the Erk1/2 and Akt signaling pathways. Treatment with high doses of methylcobalamin ameliorates symptoms and negative electrophysiological findings in animal models of peripheral nerve neuropathy and in patients with carpal tunnel syndrome and amyotrophic lateral sclerosis. Thus, high-dose methylcobalamin has great potential for treating nervous system disorders. Further investigations with methylcobalamin may help elucidate its mechanisms of action, which may further enable us to treat many nervous system disorders. PMID:24018744

  11. Strength-duration curve: a measure for assessing sensory deficit in peripheral neuropathy.

    PubMed Central

    Friedli, W G; Meyer, M

    1984-01-01

    By using an isolated constant current stimulator producing true square-wave pulses, sensory strength-duration curves were obtained at various sites by percutaneous electrical stimulation. Strength-duration curves derived from normal groups were compared to those of patients with peripheral neuropathy. Stimulus strength at sensory threshold was shown to be a reproducible measure of sensory deficit, increasing parallel to the degree of axonal failure found by conventional methods. This may be useful as a complementary method in assessing peripheral neuropathy. PMID:6323634

  12. Complicated hereditary spastic paraplegia with peripheral neuropathy, optic atrophy and mental retardation.

    PubMed

    Miyama, S; Arimoto, K; Kimiya, S; Tomi, H

    2000-08-01

    An 8-year old girl with a not previously described type of complicated hereditary spastic paraplegia (HSP) is presented. Spasticity in her lower limbs had already been recognized during infancy and worsened progressively. Severe delay in mental development was observed. Peripheral neuropathy and optic atrophy developed at 5 years of age. On brain magnetic resonance imaging, an abnormally thin corpus callosum was observed. Involvement of the fasciculus gracilis was suggested by somatosensory evoked potentials. To our knowledge, there has been no reported case of complicated HSP with peripheral neuropathy, optic atrophy and mental retardation so far. We postulate that our patient is a sporadic case of not previously described complicated HSP. PMID:11071149

  13. Bortezomib-Induced Painful Peripheral Neuropathy: An Electrophysiological, Behavioral, Morphological and Mechanistic Study in the Mouse

    PubMed Central

    Bardini, Michela; Fazio, Grazia; Chiorazzi, Alessia; Meregalli, Cristina; Oggioni, Norberto; Shanks, Kathleen; Quartu, Marina; Serra, Maria Pina; Sala, Barbara; Cavaletti, Guido; Dorsey, Susan G.

    2013-01-01

    Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG) and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations was found as well as

  14. A prospective surveillance model for physical rehabilitation of women with breast cancer: chemotherapy-induced peripheral neuropathy.

    PubMed

    Stubblefield, Michael D; McNeely, Margaret L; Alfano, Catherine M; Mayer, Deborah K

    2012-04-15

    Chemotherapy-induced peripheral neuropathy (CIPN) results from damage to or dysfunction of the peripheral nerves. The development of CIPN is anticipated for the majority of breast cancer patients who receive neurotoxic chemotherapy, depending on the agent used, dose, and schedule. Sensory symptoms often predominate and include numbness, tingling, and distal extremity pain. Weakness, gait impairment, loss of functional abilities, and other deficits may develop with more severe CIPN. This article outlines a prospective surveillance model for physical rehabilitation of women with breast cancer who develop CIPN. Rehabilitative efforts for CIPN start at the time of breast cancer diagnosis and treatment planning. The prechemotherapy evaluation identifies patients with preexisting peripheral nervous system disorders that may place them at higher risk for the development of CIPN. This clinical evaluation should include a history focusing on symptoms and functional activities as well as a physical examination that objectively assesses the patient's strength, sensation, reflexes, and gait. Ongoing surveillance following the initiation of a neurotoxic agent is important to monitor for the development and progression of symptoms associated with CIPN, and to ensure its resolution over the long term. CIPN is managed best by a multidisciplinary team approach. Early identification of symptoms will ensure appropriate referral and timely symptom management. The prospective surveillance model promotes a patient-centered approach to care, from pretreatment through survivorship and palliative care. In this way, the model offers promise in addressing and minimizing both the acute and long-term morbidity associated with CIPN. PMID:22488699

  15. Phase 2 Study of Acupuncture-Like Transcutaneous Nerve Stimulation for Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

    Wong, Raimond; Major, Pierre; Sagar, Stephen

    2016-06-01

    A prospective phase 2 study was conducted to evaluate the clinical utility of acupuncture-like transcutaneous nerve stimulation (ALTENS) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Eligible cancer patients had a < 2 ECOG performance score, received neurotoxic chemotherapy, and developed CIPN symptoms for > two months. Randomization was used to eliminate bias in patient selection for ALTENS and was not to compare the effectiveness between the two treatments.ALTENS treatments were delivered using Codetron units. Bilateral acupuncture points included LI4 and LIV3, plus LI11 or ST36 were stimulated. Acupuncture treatments were administered to CV6, SP6, ST6, LI11, Bafeng, Baxie and selective Jing points bilaterally. Twelve treatments were delivered twice weekly over 6 to 8 weeks. The Modified Total Neuropathy Score (mTNS), Numbness Score, and Edmonton Symptom Assessment Score (ESAS) were assessed at baseline, treatment completion, plus at 3 and 6 months follow-up. The primary study endpoint was mTNS score at 6 months. We planned to recruit 23 patients into each group. After 30 patients were recruited, 2 were lost to follow-up at 3 months in the ALTENS group and 3 in the acupuncture group. The research team decided to recruit all remaining consecutive patients only to the ALTENS group to ensure an adequate evaluation of ALTENS, the primary object of evaluation. There were 27 patients in the ALTENS group, with an average symptom duration of 10 months after chemotherapy. Twenty four and 23 patients completed the 3 and 6 month follow-up respectively. The median mTNS scores were 7.1, 4.0, 3.6 and 3.1 at baseline, treatment completion, 3 and 6 months follow-up, respectively. One-way ANOVA analysis showed a significant improvement in mTNS scores (p<0.001) at 6 months. Numbness scores were also significantly improved at 6 months. ESAS pain scores and perception of well-being scores analyses were inconclusive. There were no significant reported side

  16. Expenditures in the elderly with peripheral neuropathy: Where should we focus cost-control efforts?

    PubMed

    Callaghan, Brian C; Burke, James F; Rodgers, Ann; McCammon, Ryan; Langa, Kenneth M; Feldman, Eva L; Kerber, Kevin A

    2013-10-01

    To optimize care in the evaluation of peripheral neuropathy, we sought to define which tests drive expenditures and the role of the provider type. We investigated test utilization and expenditures by provider type in those with incident neuropathy in a nationally representative elderly, Medicare population. Multivariable logistic regression was used to determine predictors of MRI and electrodiagnostic utilization. MRIs of the neuroaxis and electrodiagnostic tests accounted for 88% of total expenditures. Mean and aggregate diagnostic expenditures were higher in those who saw a neurologist. Patients who saw a neurologist were more likely to receive an MRI and an electrodiagnostic test. MRIs and electrodiagnostic tests are the main contributors to expenditures in the evaluation of peripheral neuropathy, and should be the focus of future efficiency efforts. PMID:24175158

  17. Prevalence and related risk-factors of peripheral neuropathy in children with insulin-dependent diabetes mellitus

    PubMed Central

    Hasani, Nasibeh; Khosrawi, Saeid; Hashemipour, Mahin; Haghighatiyan, Mania; Javdan, Zahra; Taheri, Mohamad Hadi; Kelishadi, Roya; Amini, Massoud; Barekatein, Reihaneh

    2013-01-01

    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. PMID:23914216

  18. 77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ...-modifying agents, and clinical trial design. FDA intends to take this information into account in developing... painful peripheral neuropathies amenable to treatment with disease-modifying agents, and clinical trial... HUMAN SERVICES Food and Drug Administration Clinical Development Programs for Disease-Modifying...

  19. Familial congenital anterior cervical hypertrichosis associated with peripheral sensory and motor neuropathy--a new syndrome?

    PubMed

    Trattner, A; Hodak, E; Sagie-Lerman, T; David, M; Nitzan, M; Garty, B Z

    1991-11-01

    We present three patients with familial congenital hypertrichosis localized to the anterior cervical region, associated with peripheral sensory and motor neuropathy. This association may represent a new neurocutaneous syndrome. The association of anterior midline cutaneous lesions with an underlying malformation is discussed. PMID:1666396

  20. 78 FR 54763 - Disease Associated With Exposure to Certain Herbicide Agents: Peripheral Neuropathy

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-06

    ... Federal Register (77 FR 47795), to amend its adjudication regulations regarding presumptive service... Vietnam (77 FR 47924). This notice provided an explanation of VA's decision to not create presumptions of... peripheral neuropathy associated with exposure to certain herbicides. See 77 FR 47795. As such, the...

  1. Disordered pigmentation, spastic paraparesis and peripheral neuropathy in three siblings: a new neurocutaneous syndrome.

    PubMed Central

    Abdallat, A; Davis, S M; Farrage, J; McDonald, W I

    1980-01-01

    Three siblings in a Jordanian family presented with a distinctive syndrome consisting of disordered skin and hair pigmentation, progressive spastic paraparesis and peripheral neuropathy. Sural nerve biopsy revealed axonal degeneration and skin biopsy showed abnormal epidermal pigmentation. Skin fibroblast repair studies were normal. No underlying biochemical defect has been found in this previously undescribed neurocutaneous syndrome. Images PMID:7441281

  2. Automated Peripheral Neuropathy Assessment Using Optical Imaging and Foot Anthropometry.

    PubMed

    Siddiqui, Hafeez-U R; Spruce, Michelle; Alty, Stephen R; Dudley, Sandra

    2015-08-01

    A large proportion of individuals who live with type-2 diabetes suffer from plantar sensory neuropathy. Regular testing and assessment for the condition is required to avoid ulceration or other damage to patient's feet. Currently accepted practice involves a trained clinician testing a patient's feet manually with a hand-held nylon monofilament probe. The procedure is time consuming, labor intensive, requires special training, is prone to error, and repeatability is difficult. With the vast increase in type-2 diabetes, the number of plantar sensory neuropathy sufferers has already grown to such an extent as to make a traditional manual test problematic. This paper presents the first investigation of a novel approach to automatically identify the pressure points on a given patient's foot for the examination of sensory neuropathy via optical image processing incorporating plantar anthropometry. The method automatically selects suitable test points on the plantar surface that correspond to those repeatedly chosen by a trained podiatrist. The proposed system automatically identifies the specific pressure points at different locations, namely the toe (hallux), metatarsal heads and heel (Calcaneum) areas. The approach is generic and has shown 100% reliability on the available database used. The database consists of Chinese, Asian, African, and Caucasian foot images. PMID:26186748

  3. Murine immunodeficiency virus-induced peripheral neuropathy and the associated cytokine responses.

    PubMed

    Cao, Ling; Butler, M Brady; Tan, Leonard; Draleau, Kyle S; Koh, Woon Yuen

    2012-10-01

    Distal symmetrical polyneuropathy is the most common form of HIV infection-associated peripheral neuropathy and is often associated with pain. C57BL/6 (B6) mice infected with LP-BM5, a murine retroviral isolate, develop a severe immunodeficiency syndrome similar to that in humans infected with HIV-1, hence the term murine AIDS. We investigated the induction of peripheral neuropathy after LP-BM5 infection in B6 mice. Infected B6 mice, like HIV-infected humans, exhibited behavioral (increased sensitivity to mechanical and heat stimuli) and pathological (transient loss of intraepidermal nerve fibers) signs of peripheral neuropathy. The levels of viral gag RNA were significantly increased in all tissues tested, including spleen, paw skin, lumbar dorsal root ganglia, and lumbar spinal cord, postinfection (p.i.). Correlated with the development of peripheral neuropathy, the tissue levels of several cytokines, including IFN-γ, IL-1β, IL-6, and IL-12, were significantly elevated p.i. These increases had cytokine-specific and tissue-specific profiles and kinetics. Further, treatment with the antiretroviral agent zidovudine either significantly reduced or completely reversed the aforementioned behavioral, pathologic, and cytokine changes p.i. These data suggest that LP-BM5 infection is a potential mouse model of HIV-associated distal symmetrical polyneuropathy that can be used for investigating the roles of various cytokines in infection-induced neuropathic pain. Further investigation of this model could give a better understanding of, and lead to more effective treatments for, HIV infection-associated painful peripheral neuropathy. PMID:22956581

  4. Peripheral neuropathy in chronic liver disease: clinical, electrodiagnostic, and nerve biopsy findings

    PubMed Central

    Knill-Jones, R. P.; Goodwill, C. J.; Dayan, A. D.; Williams, Roger

    1972-01-01

    In a prospective study of 70 unselected patients with chronic liver disease, clinical signs of a peripheral neuropathy were observed in 13 patients. Abnormal nerve conduction was demonstrated in nine of these and in one further patient who had no abnormal neurological signs. The occurrence of a neuropathy (in patients with cryptogenic cirrhosis, haemochromatosis, active chronic hepatitis as well as in alcoholic cirrhosis) could not be related to liver function, although it was associated with higher IgA and IgM values. Clinical diabetes was present in six of the 14 patients with neuropathy but there was no relation in the non-diabetic patients between neuropathy and minor impairment of carbohydrate tolerance. Those with neuropathy had a significantly higher incidence of oesophageal varices and there was also a relationship to a history of previous encephalopathy. Sural nerve biopsy was carried out on 14 patients, eight of whom had clinical or electrodiagnostic evidence of neuropathy. Single nerve fibres were examined by teasing and in all nerves histological evidence was found of an indolent process which had damaged whole Schwann cells and which resulted in demyelination and remyelination. Diabetic angiopathy was not seen and axonal degeneration, which was never severe, was found in all disease groups equally. Images PMID:4337271

  5. Alternative Quantitative Tools in the Assessment of Diabetic Peripheral and Autonomic Neuropathy.

    PubMed

    Vinik, A I; Casellini, C; Névoret, M-L

    2016-01-01

    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. PMID:27133153

  6. Link between peripheral neuropathy and monoclonal dysglobulinemia: a study of 66 cases.

    PubMed

    Vallat, J M; Jauberteau, M O; Bordessoule, D; Yardin, C; Preux, P M; Couratier, P

    1996-05-01

    The association of peripheral neuropathy (PN) and monoclonal dysglobulinemia has often been reported, although a direct link between the two is not readily established. Linkage is generally based on consideration of the clinical, electrophysiological and immunological findings along with details of the course. We report here a study of 66 of our own cases which benefitted from immunological and immunopathological analyses of serum. In 62 of these cases, histological and immunopathological examinations of nerve biopsy specimens were realized. Such a discussion about a link between the dysglobulinemia and the peripheral neuropathy is of clinical interest as it provides information for decisions about the continuation of potentially neurotoxic chemotherapy. In this prospective study conducted on a case by case basis, the origin of the neuropathy, whether due to the chemotherapy, the dysimmune process, the presence of abnormal immunoglobulins in the nerve, amyloid deposits, infiltration of nerve parenchyme by abnormal cells, or a combination of one or more of these mechanisms, could be determined in most cases. We divided our population of 66 patients into 4 etiological groups: group 1: direct link (56.1%), group 2: indirect link (12.7%), group 3: no link (10.6%), group 4: doubtful link (21.2%). In group 1 we found a statistically significant association between the peripheral neuropathy and an IgM kappa MGUS. PMID:8782166

  7. A study of pathology of a bovine primary peripheral myelinopathy with features of tomaculous neuropathy.

    PubMed

    Hill, B D; Prior, H; Blakemore, W F; Black, P F

    1996-01-01

    Cases of a bovine neuropathy are reported in which peripheral nerves show "sausage-shaped" thickenings of the myelin sheaths at different sites of the internode. Clinical signs of dysphagia and chronic rumenal bloat developed after weaning which were attributable to bilateral vagus nerve degeneration. Trunks of the sciatic nerves and brachial plexuses were similarly affected with the animal adopting a weak shuffling gait. Affected animals were the progeny of sire-daughter matings. The lesions are similar to those seen in the tomaculous neuropathies of man. The present study is believed to be the first report of this lesion occurring in domestic animals. PMID:8740237

  8. Efficacy of low level laser therapy on painful diabetic peripheral neuropathy

    PubMed Central

    CG, Shashi Kumar; Hande, H Manjunath; Vidyasagar, Sudha; Rao, Karthik; Rajagopal, K.V

    2015-01-01

    Background & aims: 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/cm2 on the plantar and dorsum of the foot and 3.4j/cm2 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 p<0.05 Results: The result analysis showed significant reduction in Pain using VAS scale (6.47 ± 0.84 to 1.21 ± 0.78 (p<0.001), MNSI (5.52 ± 1.26 to 2.71 ± 0.97 (reduction in Vibration perception threshold (32.68 ± 6.08 to 24.84 ± 4.29 (<0.001) and a significant increase in the temperature from baseline to post intervention (30.01 ± 2.11 to 31.75 ± 1.03 (p<0. 001). Conclusion: In the present study, Low level laser therapy was found to be effective in type 2 DM with peripheral neuropathy. PMID:26557734

  9. EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy.

    PubMed

    Lauria, G; Cornblath, D R; Johansson, O; McArthur, J C; Mellgren, S I; Nolano, M; Rosenberg, N; Sommer, C

    2005-10-01

    Skin biopsy has become a widely used tool to investigate small calibre sensory nerves including somatic unmyelinated intraepidermal nerve fibres (IENF), dermal myelinated nerve fibres, and autonomic nerve fibres in peripheral neuropathies and other conditions. Different techniques for tissue processing and nerve fibre evaluation have been used. In March 2004, a Task Force was set up under the auspices of the European Federation of Neurological Societies (EFNS) with the aim of developing guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathies. We searched the Medline database from 1989, the year of the first publication describing the innervation of human skin using immunostaining with anti-protein-gene-product 9.5 (PGP 9.5) antibodies, to 31 March 2005. All pertinent papers were rated according to the EFNS guidance. The final version of the guidelines was elaborated after consensus amongst members of the Task Force was reached. For diagnostic purposes in peripheral neuropathies, we recommend performing a 3-mm punch skin biopsy at the distal leg and quantifying the linear density of IENF in at least three 50-mum thick sections per biopsy, fixed in 2% PLP or Zamboni's solution, by bright-field immunohistochemistry or immunofluorescence with anti-PGP 9.5 antibodies (level A recommendation). Quantification of IENF density closely correlated with warm and heat-pain threshold, and appeared more sensitive than sensory nerve conduction study and sural nerve biopsy in diagnosing small-fibre sensory neuropathy. Diagnostic efficiency and predictive values of this technique were very high (level A recommendation). Confocal microscopy may be particularly useful to investigate myelinated nerve fibres, dermal receptors and dermal annex innervation. In future, the diagnostic yield of dermal myelinated nerve fibre quantification and of sweat gland innervation should be addressed. Longitudinal studies of IENF density and regeneration rate are warranted to

  10. [Physiological approach to peripheral neuropathy. Conventional nerve conduction studies and magnetic motor root stimulation].

    PubMed

    Ugawa, Yoshikazu

    2004-11-01

    In this communication, I first show some points we should mind in the conventional peripheral nerve conduction studies and later present clinical usefulness of motor root stimulation for peripheral neuropathy. CONVENTIONAL NERVE CONDUCTION STUDIES (NCS): The most important point revealed by the conventional NCSs is whether neuropathy is due to axonal degeneration or demyelinating process. Precise clinical examination with this neurophysiological information leads us to a diagnosis and treatment. Poor clinical examination makes these findings useless. Long standing axonal degeneration sometimes induces secondary demyelination at the most distal part of involved nerves. On the other hand, severe segmental demyelination often provokes secondary axonal degeneration at distal parts to the site of demyelination. These secondary changes show the same abnormal neurophysiological findings as those of the primary involvement. We should be careful of this possibility when interpreting the results of NCS. NCS of sensory nerves is not good at revealing demyelinating process. Mild temporal dispersion of potentials often reduces an amplitude of SNAP or loss of responses, which usually suggests axonal degeneration, because of short duration of sensory nerve potentials. MOTOR ROOT STIMULATION IN PERIPHERAL NEUROPATHY: Magnetic stimulation with a coil placed over the spine activates motor roots and evokes EMG responses from upper and lower limb muscles. The site of activation with this method was determined to be where the motor roots exit from the spinal canal (intervertebral foramina) (J Neurol Neurosurg Psychiatry 52 (9): 1025-1032, 1989) because induced currents are very dense at such a foramen made by electric resistant bones. In several kinds of peripheral neuropathy, this method has been used to detect a lesion at a proximal part of the peripheral nerves which can not be detected by the conventional NCSs. I present a few cases in whom motor root stimulation had a clinical

  11. Identification of Genetic Causes of Inherited Peripheral Neuropathies by Targeted Gene Panel Sequencing.

    PubMed

    Nam, Soo Hyun; Hong, Young Bin; Hyun, Young Se; Nam, Da Eun; Kwak, Geon; Hwang, Sun Hee; Choi, Byung-Ok; Chung, Ki Wha

    2016-05-31

    Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115 samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely-pathogenic mutations in eight genes from 25 patients (17 families). Of them, eight mutations were unreported variants. Of particular interest, this study revealed several very rare mutations in the SPTLC2, DCTN1, and MARS genes. In addition, the effectiveness of the detection of CMT1A was confirmed by comparing five 17p12-nonduplicated controls and 15 CMT1A cases. In conclusion, we developed a gene panel for one step genetic diagnosis of IPN. It seems that its time- and cost-effectiveness are superior to previous tiered-genetic diagnosis algorithms, and it could be applied as a genetic diagnostic system for inherited peripheral neuropathies. PMID:27025386

  12. Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway

    PubMed Central

    Li, Qing-rong; Wang, Zhuo; Zhou, Wei; Fan, Shou-rui; Ma, Run; Xue, Li; Yang, Lu; Li, Ya-shan; Tan, Hong-li; Shao, Qing-hua; Yang, Hong-ying

    2016-01-01

    Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway. PMID:27073391

  13. Identification of Genetic Causes of Inherited Peripheral Neuropathies by Targeted Gene Panel Sequencing

    PubMed Central

    Nam, Soo Hyun; Hong, Young Bin; Hyun, Young Se; Nam, Da Eun; Kwak, Geon; Hwang, Sun Hee; Choi, Byung-Ok; Chung, Ki Wha

    2016-01-01

    Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115 samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely-pathogenic mutations in eight genes from 25 patients (17 families). Of them, eight mutations were unreported variants. Of particular interest, this study revealed several very rare mutations in the SPTLC2, DCTN1, and MARS genes. In addition, the effectiveness of the detection of CMT1A was confirmed by comparing five 17p12-nonduplicated controls and 15 CMT1A cases. In conclusion, we developed a gene panel for one step genetic diagnosis of IPN. It seems that its time- and cost-effectiveness are superior to previous tiered-genetic diagnosis algorithms, and it could be applied as a genetic diagnostic system for inherited peripheral neuropathies. PMID:27025386

  14. Beneficial effect of TNF-α inhibition on diabetic peripheral neuropathy

    PubMed Central

    2013-01-01

    Background Tumor necrosis factor-α (TNF-α) is an important inflammatory factor produced by activated macrophages and monocytes and plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN). To evaluate the effect of TNF-α signaling suppression and the potential of TNF-α in the treatment of DPN, a recombinant human TNF-α receptor-antibody fusion protein (rhTNFR:Fc) was used. We focused on the pathophysiology of the sciatic nerve and examined the expression of myelin basic protein (MBP) under DPN status with or without TNF-α inhibition. Methods The DPN rat model was generated by intraperitoneal injection of streptozotocin and by feeding with a high-fat, high-sugar diet. The nerve conduction velocity (NCV) in sciatic nerve of rat was monitored over a period of four weeks. The histopathological changes in nerve tissue were examined through traditional tissue histology and ultrastructure transmission electron microscopy (TEM). The expression of MBP was examined through western blot analysis. Results The DPN induced rats showed significant signs of nerve damage including lower NCV, demyelination of nerve fibers, disorganization of lamellar and axonal structures, and decreased expression of MBP in the nerve tissue. The inhibition of TNF-α in the DPN rats resulted in a significant recovery from those symptoms compared to the DPN rats. Conclusions Our study demonstrates that TNF-α plays a key role in the pathogenesis of DPN and its inhibition by rhTNFR:Fc can prove to be a useful therapeutic strategy for the treatment of and/or prevention from DPN symptoms. PMID:23735240

  15. Physical activity, glycemic control, and diabetic peripheral neuropathy: a national sample.

    PubMed

    Loprinzi, Paul D; Hager, Kathy K; Ramulu, Pradeep Y

    2014-01-01

    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. PMID:24090951

  16. Pharmacogenetics of nucleoside reverse-transcriptase inhibitor-associated peripheral neuropathy.

    PubMed

    Kallianpur, Asha R; Hulgan, Todd

    2009-04-01

    Peripheral neuropathy is an important complication of antiretroviral therapy. Nucleoside reverse-transcriptase inhibitor (NRTI)-associated mitochondrial dysfunction, inflammation and nutritional factors are implicated in its pathogenesis. Pharmacogenetic and genomic studies investigating NRTI neurotoxicity have only recently become possible via the linkage of HIV clinical studies to large DNA repositories. Preliminary case-control studies using these resources suggest that host mitochondrial DNA haplogroup polymorphisms in the hemochromatosis gene and proinflammatory cytokine genes may influence the risk of peripheral neuropathy during antiretroviral therapy. These putative risk factors await confirmation in other HIV-infected populations but they have strong biological plausibility. Work to identify underlying mechanisms for these associations is ongoing. Large-scale studies incorporating clearly defined and validated methods of neuropathy assessment and the use of novel laboratory models of NRTI-associated neuropathy to clarify its pathophysiology are now needed. Such investigations may facilitate the development of more effective strategies to predict, prevent and ameliorate this debilitating treatment toxicity in diverse clinical settings. PMID:19374518

  17. Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2015-05-01

    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

  18. Neuroactive steroid treatment modulates myelin lipid profile in diabetic peripheral neuropathy.

    PubMed

    Mitro, Nico; Cermenati, Gaia; Brioschi, Elisabetta; Abbiati, Federico; Audano, Matteo; Giatti, Silvia; Crestani, Maurizio; De Fabiani, Emma; Azcoitia, Inigo; Garcia-Segura, Luis Miguel; Caruso, Donatella; Melcangi, Roberto Cosimo

    2014-09-01

    Diabetic peripheral neuropathy causes a decrease in the levels of dihydroprogesterone and 5α-androstane-3α,17β-diol (3α-diol) in the peripheral nerves. These two neuroactive steroids exert protective effects, by mechanisms that still remain elusive. We have previously shown that the activation of Liver X Receptors improves the peripheral neuropathic phenotype in diabetic rats. This protective effect is accompanied by the restoration to control values of the levels of dihydroprogesterone and 3α-diol in peripheral nerves. In addition, activation of these receptors decreases peripheral myelin abnormalities by improving the lipid desaturation capacity, which is strongly blunted by diabetes, and ultimately restores the myelin lipid profile to non-diabetic values. On this basis, we here investigate whether dihydroprogesterone or 3α-diol may exert their protective effects by modulating the myelin lipid profile. We report that both neuroactive steroids act on the lipogenic gene expression profile in the sciatic nerve of diabetic rats, reducing the accumulation of myelin saturated fatty acids and promoting desaturation. These changes were associated with a reduction in myelin structural alterations. These findings provide evidence that dihydroprogesterone and 3α-diol are protective agents against diabetic peripheral neuropathy by regulating the de novo lipogenesis pathway, which positively influences myelin lipid profile. PMID:24607810

  19. Unraveling the Pathogenesis of HIV Peripheral Neuropathy: Insights from a Simian Immunodeficiency Virus Macaque Model

    PubMed Central

    Mangus, Lisa M.; Dorsey, Jamie L.; Laast, Victoria A.; Ringkamp, Matthias; Ebenezer, Gigi J.; Hauer, Peter; Mankowski, Joseph L.

    2014-01-01

    Peripheral neuropathy (PN) is the most frequent neurologic complication in individuals infected with human immunodeficiency virus (HIV). It affects over one third of infected patients, including those receiving effective combination antiretroviral therapy. The pathogenesis of HIV-associated peripheral neuropathy (HIV-PN) remains poorly understood. Clinical studies are complicated because both HIV and antiretroviral treatment cause damage to the peripheral nervous system. To study HIV-induced peripheral nervous system (PNS) damage, a unique simian immunodeficiency virus (SIV)/pigtailed macaque model of HIV-PN that enabled detailed morphologic and functional evaluation of the somatosensory pathway throughout disease progression was developed. Studies in this model have demonstrated that SIV induces key pathologic features that closely resemble HIV-induced alterations, including inflammation and damage to the neuronal cell bodies in somatosensory ganglia and decreased epidermal nerve fiber density. Insights generated in the model include: finding that SIV alters the conduction properties of small, unmyelinated peripheral nerves; and that SIV impairs peripheral nerve regeneration. This review will highlight the major findings in the SIV-infected pigtailed macaque model of HIV-PN, and will illustrate the great value of a reliable large animal model to show the pathogenesis of this complex, HIV-induced disorder of the PNS. PMID:24615443

  20. Late-onset MNGIE without peripheral neuropathy due to incomplete loss of thymidine phosphorylase activity.

    PubMed

    Massa, Roberto; Tessa, Alessandra; Margollicci, Maria; Micheli, Vanna; Romigi, Andrea; Tozzi, Giulia; Terracciano, Chiara; Piemonte, Fiorella; Bernardi, Giorgio; Santorelli, Filippo M

    2009-12-01

    Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE) is an autosomal recessive disorder characterized by severe gastrointestinal dysmotility, cachexia, peripheral neuropathy, ptosis, ophthalmoplegia, and leukoencephalopathy with early onset and severe prognosis. Mutations in the TYMP/ECGF1 gene cause a loss of thymidine phosphorylase catalytic activity, disrupting the homeostasis of intramitochondrial nucleotide pool. We report a woman with a very late onset of MNGIE, lacking peripheral neuropathy. Thymidine phosphorylase activity was markedly reduced in cultured fibroblasts, but only mildly reduced in buffy coat, where the defect is usually detected, and plasma thymidine was mildly increased compared to typical MNGIE patients. TYMP/ECGF1 analysis detected two heterozygous mutations, including a novel missense mutation. These findings indicate that a partial loss of thymidine phosphorylase activity may induce a late-onset and incomplete MNGIE phenotype. PMID:19853446

  1. [Effects of Vitamin B12 in Patients with Amyotrophic Lateral Sclerosis and Peripheral Neuropathy].

    PubMed

    Nodera, Hiroyuki; Izumi, Yuishin; Kaji, Ryuji

    2015-09-01

    Vitamin B(12)(vB(12)) deficient is regarded as iatrogenic in some cases. Although the recommended oral intake of vB(12) has been determined, administration of vB(12) exceeding the recommended dose could have multiple pharmacological effects. "Ultra-high dose" vB(12) therapy has been used for peripheral neuropathy and amyotrophic lateral sclerosis, suggesting its promising neuroprotective effects. PMID:26329154

  2. Do Ankle Orthoses Improve Ankle Proprioceptive Thresholds or Unipedal Balance in Older Persons with Peripheral Neuropathy?

    PubMed Central

    Son, Jaebum; Ashton-Miller, James A.; Richardson, James K.

    2010-01-01

    Objective To determine whether ankle orthoses that provide medial and lateral support, and have been found to decrease gait variability in older persons with peripheral neuropathy, decrease (improve) frontal plane ankle proprioceptive thresholds or increase unipedal stance time in that same population. Design Observational study in which unipedal stance time was determined with a stopwatch, and frontal plane ankle (inversion and eversion) proprioceptive thresholds were quantified during bipedal stance with and without the ankle orthoses, in 11 older diabetic subjects with peripheral neuropathy (8 men; age 72 ± 7.1 years) using a foot cradle system which presented a series of 100 rotational stimuli. Results The subjects demonstrated no change in combined frontal plane (inversion + eversion) proprioceptive thresholds or unipedal stance time with versus without the orthoses (1.06 ± 0.56 versus 1.13 ± 0.39 degrees, respectively; p = 0.955 and 6.1 ± 6.5 versus 6.2 ± 5.4 seconds, respectively; p = 0.922). Conclusion Ankle orthoses which provide medial-lateral support do not appear to change ankle inversion/eversion proprioceptive thresholds or unipedal stance time in older persons with diabetic peripheral neuropathy. Previously identified improvements in gait variability using orthoses in this population are therefore likely related to an orthotically-induced stiffening of the ankle rather than a change in ankle afferent function. PMID:20407302

  3. Fenugreek seed extract treats peripheral neuropathy in pyridoxine induced neuropathic mice

    PubMed Central

    Moghadam, Farshad Homayouni; Vakili-Zarch, Behzad; Shafiee, Mohammad; Mirjalili, Azam

    2013-01-01

    Trigonella foenum graecum commonly known as Fenugreek exerts normoglycemic and insulinotropic effects in humans by compounds from its seed and leaf extracts. Some studies reported that treating pregnant mice with fenugreek seed could cause toxic effects on the nervous system of its pubs during developmental growth, while in some other studies neuroprotective properties were considered for it. Safety of anti-diabetic drugs for nervous system is very important because peripheral neuropathy is a common complication of diabetes and hazardous drugs could worsen it. In this study, the effect of treatment with fenugreek seed extract on the function of sciatic nerves of neuropathic mice was evaluated. Neuropathy was induced in male mice by pyridoxine intoxication. After that, animals were treated with 0.2, 2 and 20 mg/kg of hydro-alcoholic extract of fenugreek seeds for 10 days, tail flick, electrophysiological and histological assays were performed to evaluate the effect of fenugreek seed extract on function of the peripheral nerves. Our data showed that fenugreek has anti neuropathic effect and restores the function of nerve fibers. Results of electrophysiological recordings stated that the highest rate of healing was occurred in 20 mg/kg fenugreek extract treated animals. In conclusion, findings of the present study demonstrate that treatment with fenugreek seed extract can potentially facilitate healing from pyridoxine induced peripheral neuropathy in mice. PMID:26417231

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

    PubMed Central

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

    2014-01-01

    One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype. PMID:24764191

  5. Structural Basis for Induction of Peripheral Neuropathy by Microtubule-Targeting Cancer Drugs.

    PubMed

    Smith, Jennifer A; Slusher, Barbara S; Wozniak, Krystyna M; Farah, Mohamed H; Smiyun, Gregoriy; Wilson, Leslie; Feinstein, Stuart; Jordan, Mary Ann

    2016-09-01

    Peripheral neuropathy is a serious, dose-limiting side effect of cancer treatment with microtubule-targeting drugs. Symptoms present in a "stocking-glove" distribution, with longest nerves affected most acutely, suggesting a length-dependent component to the toxicity. Axonal transport of ATP-producing mitochondria along neuronal microtubules from cell body to synapse is crucial to neuronal function. We compared the effects of the drugs paclitaxel and ixabepilone that bind along the lengths of microtubules and the drugs eribulin and vincristine that bind at microtubule ends, on mitochondrial trafficking in cultured human neuronal SK-N-SH cells and on axonal transport in mouse sciatic nerves. Antiproliferative concentrations of paclitaxel and ixabepilone significantly inhibited the anterograde transport velocity of mitochondria in neuronal cells, whereas eribulin and vincristine inhibited transport only at significantly higher concentrations. Confirming these observations, anterogradely transported amyloid precursor protein accumulated in ligated sciatic nerves of control and eribulin-treated mice, but not in paclitaxel-treated mice, indicating that paclitaxel inhibited anterograde axonal transport, whereas eribulin did not. Electron microscopy of sciatic nerves of paclitaxel-treated mice showed reduced organelle accumulation proximal to the ligation consistent with inhibition of anterograde (kinesin based) transport by paclitaxel. In contrast, none of the drugs significantly affected retrograde (dynein based) transport in neuronal cells or mouse nerves. Collectively, these results suggest that paclitaxel and ixabepilone, which bind along the lengths and stabilize microtubules, inhibit kinesin-based axonal transport, but not dynein-based transport, whereas the microtubule-destabilizing drugs, eribulin and vincristine, which bind preferentially to microtubule ends, have significantly less effect on all microtubule-based axonal transport. Cancer Res; 76(17); 5115-23.

  6. Peripheral Neuropathy in Primary HIV Infection Associates with Systemic and CNS Immune Activation

    PubMed Central

    Wang, Samantha XY; Ho, Emily L.; Grill, Marie; Lee, Evelyn; Peterson, Julia; Robertson, Kevin; Fuchs, Dietmar; Sinclair, Elizabeth; Price, Richard W.; Spudich, Serena

    2014-01-01

    Background Peripheral neuropathy (PN) is a frequent complication of chronic HIV infection. We prospectively studied individuals with primary HIV infection (PHI, <1 year after transmission) to assess the presence of and laboratory associations with PN in this early stage. Methods Standardized examination and analysis of blood and cerebrospinal fluid (CSF) was performed in participants with laboratory-confirmed PHI. PN was defined as ≥1 of the following unilateral or bilateral signs: decreased distal limb position, vibration, or temperature sense, or hyporeflexia; symptomatic PN (SPN) as presence of these signs with symptoms. Analysis employed nonparametric statistics. Results 20/58 (35%) antiretroviral-naïve male subjects without diabetes evaluated at a median 107 days post HIV transmission (dpt) met criteria for PN. 13/20 (65%) of PN subjects met criteria for SPN; 6/20 (30%) had bilateral findings. PN subjects and no PN subjects (NPN) did not differ in median age, dpt, blood CD4 or CD8 counts, CSF or plasma HIV RNA levels, CSF white blood cell counts, or CSF:blood albumin ratio. PN and SPN subjects had elevated CSF neopterin (p=0.003 and p=0.0005), CSF MCP-1 (p=0.006 and p=0.01) and blood neopterin (p=0.006 and p=0.009) compared to NPN. PN subjects had a higher percentage of activated phenotype CSF CD8+ T lymphocytes than NPN subjects (p=0.009). Conclusions Signs of PN were detected by detailed neurologic exam in 35% of men enrolled in a neurological study at a median 3.5 months after HIV transmission. PN during this early period may be mediated by systemic and nervous system immune responses to HIV. PMID:24732871

  7. Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats

    PubMed Central

    Fujita, Shunsuke; Ushio, Soichiro; Ozawa, Nana; Masuguchi, Ken; Kawashiri, Takehiro; Oishi, Ryozo; Egashira, Nobuaki

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusion These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes. PMID:26536615

  8. Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention

    PubMed Central

    Grisold, Wolfgang; Cavaletti, Guido; Windebank, Anthony J.

    2012-01-01

    Peripheral neuropathies induced by chemotherapy (CIPN) are an increasingly frequent problem. Contrary to hema­tologic adverse effects, which can be treated with hematopoetic growth factors, neither prophylaxis nor spe­cific treatment is available, and only symptomatic treatment can be offered. Neurotoxic drugs are becoming a major dose-limiting factor. The epidemiology is still unclear. Several drug-dependent pathogenetic mechanisms exist. CIPN are predominately sensory, length-dependent neuropathies that develop after a typical cumulative dose. Usually, the appearance of CIPN is dose dependent, although in at least 2 drugs (oxaliplatin and taxanes), immediate toxic effects occur. The most frequent substances causing CIPN are platin compounds, vinka alkaloids, taxanes, and bortezomib and thalidomide. The role of synergistic neurotoxicity caused by previously given chemo­therapies and concomitant chemotherapies and the role pre-existent neuropathy on the development of a CIPN is not clear. As the number of long-term cancer survivors increases and a new focus on long-term effects of chemotherapy-induced neuropathies emerge, concepts of rehabili­tation need to be implemented to improve the patients’ functions and quality of life. PMID:23095830

  9. Peripheral nerve disease in pregnancy.

    PubMed

    Klein, Autumn

    2013-06-01

    Neuropathies during pregnancy and the postpartum period are common and are usually due to compression around pregnancy and childbirth. The most common peripheral neuropathies are Bell's palsy, carpal tunnel syndrome (CTS), and lower extremity neuropathies. Although most neuropathies are usually reversible, associated disabilities or morbidities can limit functioning and require therapy. Nerve conduction study tests and imaging should only be considered if symptoms are unusual or prolonged. Some neuropathies may be associated with preeclampsia or an inherent underlying neuropathy that increases the risk of nerve injury. All neuropathies in pregnancy should be followed as some may be persistent and require follow-up. PMID:23563878

  10. Neuroinflammation in the peripheral nerve: Cause, modulator, or bystander in peripheral neuropathies?

    PubMed Central

    2015-01-01

    The role of innate and adaptive inflammation as a primary driver or modifier of neuropathy in premorbidly normal nerves, and as a critical player in amplifying neuropathies of other known causes (e.g., genetic, metabolic) is incompletely understood and under‐researched, despite unmet clinical need. Also, cellular and humoral components of the adaptive and innate immune system are substantial disease modifying agents in the context of neuropathies and, at least in some neuropathies, there is an identified tight interrelationship between both compartments of the immune system. Additionally, the quadruple relationship between Schwann cell, axon, macrophage, and endoneurial fibroblast, with their diverse membrane bound and soluble signalling systems, forms a distinct focus for investigation in nerve diseases with inflammation secondary to Schwann cell mutations and possibly others. Identification of key immunological effector pathways that amplify neuropathic features and associated clinical symptomatology including pain should lead to realistic and timely possibilities for translatable therapeutic interventions using existing immunomodulators, alongside the development of novel therapeutic targets. GLIA 2016;64:475–486 PMID:26250643

  11. Association of comorbidities with increasing severity of peripheral neuropathy in diabetes mellitus

    PubMed Central

    Sachedina, Shafina; Toth, Cory

    2013-01-01

    AIM: To analyze a large population of patients with diabetes and peripheral neuropathy (PN) to determine other meaningful comorbid etiologies for PN. METHODS: Peripheral Neuropathy is a common complication of type 1 and 2 diabetes mellitus; however, other potential causes for PN may be co-existing in patients with diabetes. A prospective cohort study was performed to assess patients with diabetes and PN. We compared patients having PN due solely to diabetes with patients possessing co-existing comorbidities, performing clinical (Toronto Clinical Scoring System and the Utah Early Neuropathy Scale), laboratory and electrophysiological assessments in all patients. RESULTS: Patients with either type 1 or 2 diabetes mellitus and co-existing comorbidities did not have more severe clinical or electrophysiological PN phenotypes overall. However, in patients with type 1 diabetes, presence of a lipid disorder was associated with greater PN severity. In type 2 diabetes patients, both a lipid disorder and cobalamin deficiency were associated with greater PN severity. There was no additive effect upon PN severity with presence of three or more comorbid etiologies. CONCLUSION: The presence of specific, and not general, comorbidities in patients with type 1 or 2 diabetes corresponds with greater PN severity. PMID:23961324

  12. The search for treatments to reduce chemotherapy-induced peripheral neuropathy.

    PubMed

    Pachman, Deirdre R; Loprinzi, Charles L; Grothey, Axel; Ta, Lauren E

    2014-01-01

    Oxaliplatin, a commonly used chemotherapeutic agent, is associated with both acute and chronic neurotoxicity. Chronic sensory neuropathy can be dose limiting and may have detrimental effects on patients' quality of life. Preclinical studies provide an understanding of the pathophysiology of chemotherapy-induced peripheral neuropathy (CIPN) and may be important for developing effective preventative interventions. In this issue of the JCI, Coriat and colleagues used an animal model and a human pilot trial to evaluate the use of mangafodipir to reduce CIPN. Although many pilot clinical studies have reported promising data, larger clinical trials have repeatedly been unable to confirm these preliminary results. Thus, no agents are currently clinically recommended for the prevention of CIPN. PMID:24355918

  13. The search for treatments to reduce chemotherapy-induced peripheral neuropathy

    PubMed Central

    Pachman, Deirdre R.; Loprinzi, Charles L.; Grothey, Axel; Ta, Lauren E.

    2013-01-01

    Oxaliplatin, a commonly used chemotherapeutic agent, is associated with both acute and chronic neurotoxicity. Chronic sensory neuropathy can be dose limiting and may have detrimental effects on patients’ quality of life. Preclinical studies provide an understanding of the pathophysiology of chemotherapy-induced peripheral neuropathy (CIPN) and may be important for developing effective preventative interventions. In this issue of the JCI, Coriat and colleagues used an animal model and a human pilot trial to evaluate the use of mangafodipir to reduce CIPN. Although many pilot clinical studies have reported promising data, larger clinical trials have repeatedly been unable to confirm these preliminary results. Thus, no agents are currently clinically recommended for the prevention of CIPN. PMID:24355918

  14. The Influence of Peripheral Neuropathy, Gender, and Obesity on the Postural Stability of Patients with Type 2 Diabetes Mellitus

    PubMed Central

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

    2014-01-01

    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

  15. Peripheral neuropathy via mutant tRNA synthetases: Inhibition of protein translation provides a possible explanation.

    PubMed

    Storkebaum, Erik

    2016-09-01

    Recent evidence indicates that inhibition of protein translation may be a common pathogenic mechanism for peripheral neuropathy associated with mutant tRNA synthetases (aaRSs). aaRSs are enzymes that ligate amino acids to their cognate tRNA, thus catalyzing the first step of translation. Dominant mutations in five distinct aaRSs cause Charcot-Marie-Tooth (CMT) peripheral neuropathy, characterized by length-dependent degeneration of peripheral motor and sensory axons. Surprisingly, loss of aminoacylation activity is not required for mutant aaRSs to cause CMT. Rather, at least for some mutations, a toxic-gain-of-function mechanism underlies CMT-aaRS. Interestingly, several mutations in two distinct aaRSs were recently shown to inhibit global protein translation in Drosophila models of CMT-aaRS, by a mechanism independent of aminoacylation, suggesting inhibition of translation as a common pathogenic mechanism. Future research aimed at elucidating the molecular mechanisms underlying the translation defect induced by CMT-mutant aaRSs should provide novel insight into the molecular pathogenesis of these incurable diseases. PMID:27352040

  16. Abnormal Nerve Conduction Study Findings Indicating the Existence of Peripheral Neuropathy in Multiple Sclerosis and Neuromyelitis Optica

    PubMed Central

    Warabi, Yoko; Yamazaki, Mikihiro; Shimizu, Toshio; Nagao, Masahiro

    2013-01-01

    Objective. Chronic inflammatory demyelinating polyneuropathy (CIDP) has been reported in patients with multiple sclerosis (MS). However, there have been limited reports of peripheral neuropathy as a complication of neuromyelitis optica (NMO). In this paper, we showed the characteristics and differences between peripheral neuropathy as a complication of MS and NMO. Method. We analyzed a series of 58 MS and 28 NMO patients and evaluated nerve conduction studies (NCS) in 21 MS and 5 NMO patients. Results. Six of the 58 MS and 3 of the 28 NMO patients revealed abnormal NCS findings. Three (5.2%) of the 58 MS patients fulfilled the criteria for CIDP. One (3.6%) of the 28 NMO patients showed peripheral neuropathy at the same time of NMO relapse, although CIDP was not seen in NMO. The other 5 (3 MS and 2 NMO) patients were complicated with neuropathy caused by concomitant diabetes mellitus and Sjögren's syndrome. Conclusion. Frequency of abnormal NCS findings might exhibit no significant difference between MS and NMO, although the cause and pathophysiology of peripheral neuropathy were different in MS and in NMO. There might be a group of NMO who were affected simultaneously in the central and peripheral nervous tissues. PMID:24308009

  17. The older adult with diabetes: peripheral neuropathy and walking for health.

    PubMed

    Cuaderes, Elena; Lamb, W Lyndon; Alger, Anne

    2014-06-01

    The rate at which older individuals are being diagnosed with diabetes is increasing. Therefore, the ability of older persons with diabetes to successfully age in place is of concern for health care professionals. Diabetic peripheral neuropathy can cause changes to the foot and ankle such as loss of protective sensation, joint dislocations and fractures, and formation of cracks and fissures. With special attention to their needs, practitioners can tell older people with diabetes that walking for health can be safe and without problems and can contribute to their ability to spend the rest of their lives in their own home. PMID:24846466

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

    PubMed Central

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

    2015-01-01

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

  19. Communication Barriers and the Clinical Recognition of Diabetic Peripheral Neuropathy in a Diverse Cohort of Adults: The DISTANCE Study.

    PubMed

    Adams, Alyce S; Parker, Melissa M; Moffet, Howard H; Jaffe, Marc; Schillinger, Dean; Callaghan, Brian; Piette, John; Adler, Nancy E; Bauer, Amy; Karter, Andrew J

    2016-05-01

    The purpose of this study was to explore communication barriers as independent predictors and potential mediators of variation in clinical recognition of diabetic peripheral neuropathy (DPN). In this cross-sectional analysis, we estimated the likelihood of having a DPN diagnosis among 4,436 patients with DPN symptoms. We controlled for symptom frequency, demographic and clinical characteristics, and visit frequency using a modified Poisson regression model. We then evaluated 4 communication barriers as independent predictors of clinical documentation and as possible mediators of racial/ethnic differences: difficulty speaking English, not talking to one's doctor about pain, limited health literacy, and reports of suboptimal patient-provider communication. Difficulty speaking English and not talking with one's doctor about pain were independently associated with not having a diagnosis, though limited health literacy and suboptimal patient-provider communication were not. Limited English proficiency partially attenuated, but did not fully explain, racial/ethnic differences in clinical documentation among Chinese, Latino, and Filipino patients. Providers should be encouraged to talk with their patients about DPN symptoms, and health systems should consider enhancing strategies to improve timely clinical recognition of DPN among patients who have difficult speaking English. More work is needed to understand persistent racial/ethnic differences in diagnosis. PMID:27116591

  20. Mutation analysis of genes within the dynactin complex in a cohort of hereditary peripheral neuropathies.

    PubMed

    Tey, S; Ahmad-Annuar, A; Drew, A P; Shahrizaila, N; Nicholson, G A; Kennerson, M L

    2016-08-01

    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. PMID:26662454

  1. Diabetic peripheral neuropathy assessment through texture based analysis of corneal nerve images

    NASA Astrophysics Data System (ADS)

    Silva, Susana F.; Gouveia, Sofia; Gomes, Leonor; Negrão, Luís; João Quadrado, Maria; Domingues, José Paulo; Morgado, António Miguel

    2015-05-01

    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.

  2. Comparative study of peripheral neuropathy and nerve regeneration in NOD and ICR diabetic mice.

    PubMed

    Homs, Judit; Ariza, Lorena; Pagès, Gemma; Verdú, Enrique; Casals, Laura; Udina, Esther; Chillón, Miguel; Bosch, Assumpció; Navarro, Xavier

    2011-09-01

    The non-obese diabetic (NOD) mouse was suggested as an adequate model for diabetic autonomic neuropathy. We evaluated sensory-motor neuropathy and nerve regeneration following sciatic nerve crush in NOD males rendered diabetic by multiple low doses of streptozotocin, in comparison with similarly treated Institute for Cancer Research (ICR) mice, a widely used model for type I diabetes. Neurophysiological values for both strains showed a decline in motor and sensory nerve conduction velocity at 7 and 8 weeks after induction of diabetes in the intact hindlimb. However, amplitudes of compound muscle and sensory action potentials (CMAPs and CNAPs) were significantly reduced in NOD but not in ICR diabetic mice. Morphometrical analysis showed myelinated fiber loss in highly hyperglycemic NOD mice, but no significant changes in fiber size. There was a reduction of intraepidermal nerve fibers, more pronounced in NOD than in ICR diabetic mice. Interestingly, aldose reductase and poly(ADP-ribose) polymerase (PARP) activities were increased already at 1 week of hyperglycemia, persisting until the end of the experiment in both strains. Muscle and nerve reinnervation was delayed in diabetic mice following sciatic nerve crush, being more marked in NOD mice. Thus, diabetes of mid-duration induces more severe peripheral neuropathy and slower nerve regeneration in NOD than in ICR mice. PMID:22003936

  3. Assessment of chemotherapy-induced peripheral neuropathy using the LDIFLARE technique: a novel technique to detect neural small fiber dysfunction

    PubMed Central

    Sharma, Sanjeev; Venkitaraman, Ramachandran; Vas, Prashanth R J; Rayman, Gerry

    2015-01-01

    Introduction The diagnosis and quantification of chemotherapy-induced peripheral neuropathy (CIPN) remains a challenge. Conventional methods including quantitative sensory testing (QST), nerve conduction tests, and biopsy are unable to detect subclinical changes, and do not consistently correlate with severity of patients' symptoms and functional impairment. This study aims to determine the utility of the LDI (laser Doppler imager) FLARE technique in the diagnosis of CIPN and whether it correlates with symptom severity. Materials and Methods We assessed 24 patients with established CIPN [12 due to platinum analogs (PA) and 12 to Taxanes (TX)] and 24 matched healthy controls (HC). All underwent neurophysiological examination including vibration perception threshold (VPT), sural nerve amplitude (SNAP) and conduction velocity (SNCV), LDIFLARE, and fasting biochemistry. The QLQ-CIPN20 questionnaire was used to assess symptom severity. Results HC, combined chemotherapy (CG), PA, and TX groups were matched for age, sex, BMI, and blood pressure. The LDIFLARE was significantly reduced in CG compared to HC (P =< 0.0001), whereas SNAP (P = 0.058) and SNCV (P = 0.054) were not. The LDIFLARE correlated with the QLQ-CIPN20 symptom scores in all three categories namely, CG (P =< 0.0001), PA (P = 0.001) and TX (P = 0.027) whilst, VPT, SNAP, and SNCV did not. Conclusion Our findings suggest that the LDIFLARE technique is more helpful in confirming the diagnosis of CIPN in patients with distal sensory symptoms than current commonly used methods. Moreover, this novel test fulfils the unmet need for a diagnostic test that relates to the severity of symptoms. This may be useful in quantifying early changes in small fibre function indicating early CIPN. PMID:26221574

  4. In Vivo Confocal Microscopy of the Human Cornea in the Assessment of Peripheral Neuropathy and Systemic Diseases

    PubMed Central

    Wang, Ellen F.; Misra, Stuti L.; Patel, Dipika V.

    2015-01-01

    In vivo confocal microscopy (IVCM) of the living human cornea offers the ability to perform repeated imaging without tissue damage. Studies using corneal IVCM have led to significant contributions to scientific and clinical knowledge of the living cornea in health and pathological states. Recently the application of corneal IVCM beyond ophthalmology to wider clinical and research fields has been demonstrated. Abnormalities of the corneal subbasal nerve plexus have been associated with many forms of peripheral neuropathy and Langerhans cells correlate with systemic inflammatory states. There is a rapidly growing evidence base investigating the use of corneal IVCM in many systemic conditions and a well-established evidence base for IVCM imaging of the corneal subbasal plexus in diabetic peripheral neuropathy. This paper reviews the potential use of corneal IVCM in general clinical practice as a noninvasive method of assessing peripheral neuropathies, monitoring inflammatory states and clinical therapeutic response. PMID:26770980

  5. Peripheral neuropathy with ataxia in childhood as a result of the G8363A mutation in mitochondrial DNA.

    PubMed

    Pineda, Mercedes; Solano, Abelardo; Artuch, Rafael; Andreu, Antonio L; Playan, Ana; Vilaseca, Maria A; Colomer, Jaime; Briones, Paz; Casademont, Jordi; Montoya, Julio

    2004-07-01

    Peripheral neuropathy has been identified in children with mitochondrial encephalomyopathies but not as a main clinical landmark. Here we report the clinical, electrophysiologic, biochemical, and genetic findings in a family who harbors the G8363A mutation in the tRNALys gene of mitochondrial DNA. Affected individuals presented with peripheral neuropathy and ataxia as the main clinical sign. Additional involvement included muscle weakness and multiple lipomatosis. Other common clinical characteristics associated with the G8363A mutation, such as cardiomyopathy and myoclonus epilepsy, were not observed. These findings suggest that a mitochondrial disease should be considered in the differential diagnosis of children with heredoataxic syndrome and peripheral neuropathy of unknown origin. PMID:15128915

  6. Diabetic peripheral neuropathy and its evaluation in a clinical scenario: a review.

    PubMed

    Dixit, S; Maiya, A

    2014-01-01

    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. PMID:24625937

  7. n-Hexane-related peripheral neuropathy among automotive technicians--California, 1999-2000.

    PubMed

    2001-11-16

    Solvents, glues, spray paints, coatings, silicones, and other products contain normal (n-) hexane, a petroleum distillate and simple aliphatic hydrocarbon. n-Hexane is an isomer of hexane and was identified as a peripheral neurotoxin in 1964. Since then, many cases of n-hexane-related neurotoxicity have occurred in printing plants, sandal shops, and furniture factories in Asia, Europe, and the United States. This report describes an investigation of n-hexane-associated peripheral neuropathy in an automotive technician, an occupation in which this condition has not been reported, and summarizes the results of two other case investigations in the automotive repair industry. The findings suggest that solvent manufacturers should avoid using hexane when producing automotive degreasing products, and automotive technicians should avoid regular contact with hexane-based cleaning solvents. PMID:11724159

  8. Peripheral neuropathy

    MedlinePlus

    ... disease HIV Liver infections Low levels of vitamin B12 or other vitamins Metabolic disease Poisoning due to ... may help. If you have low levels of B12 or other vitamins, your doctor may recommend supplements ...

  9. Threshold dose for peripheral neuropathy following intraoperative radiotherapy (IORT) in a large animal model

    SciTech Connect

    Kinsella, T.J.; DeLuca, A.M.; Barnes, M.; Anderson, W.; Terrill, R.; Sindelar, W.F. )

    1991-04-01

    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.

  10. Improved inherited peripheral neuropathy genetic diagnosis by whole-exome sequencing

    PubMed Central

    Drew, Alexander P; Zhu, Danqing; Kidambi, Aditi; Ly, Carolyn; Tey, Shelisa; Brewer, Megan H; Ahmad-Annuar, Azlina; Nicholson, Garth A; Kennerson, Marina L

    2015-01-01

    Inherited peripheral neuropathies (IPNs) are a group of related diseases primarily affecting the peripheral motor and sensory neurons. They include the hereditary sensory neuropathies (HSN), hereditary motor neuropathies (HMN), and Charcot-Marie-Tooth disease (CMT). Using whole-exome sequencing (WES) to achieve a genetic diagnosis is particularly suited to IPNs, where over 80 genes are involved with weak genotype–phenotype correlations beyond the most common genes. We performed WES for 110 index patients with IPN where the genetic cause was undetermined after previous screening for mutations in common genes selected by phenotype and mode of inheritance. We identified 41 missense sequence variants in the known IPN genes in our cohort of 110 index patients. Nine variants (8%), identified in the genes MFN2, GJB1, BSCL2, and SETX, are previously reported mutations and considered to be pathogenic in these families. Twelve novel variants (11%) in the genes NEFL, TRPV4, KIF1B, BICD2, and SETX are implicated in the disease but require further evidence of pathogenicity. The remaining 20 variants were confirmed as polymorphisms (not causing the disease) and are detailed here to help interpret sequence variants identified in other family studies. Validation using segregation, normal controls, and bioinformatics tools was valuable as supporting evidence for sequence variants implicated in disease. In addition, we identified one SETX sequence variant (c.7640T>C), previously reported as a putative mutation, which we have confirmed as a nonpathogenic rare polymorphism. This study highlights the advantage of using WES for genetic diagnosis in highly heterogeneous diseases such as IPNs and has been particularly powerful in this cohort where genetic diagnosis could not be achieved due to phenotype and mode of inheritance not being previously obvious. However, first tier testing for common genes in clinically well-defined cases remains important and will account for most positive

  11. Treatment of Peripheral Neuropathy in Leprosy: The Case for Nerve Decompression

    PubMed Central

    Wan, Eric L.; Rivadeneira, Andres F.; Jouvin, Renato Martinez

    2016-01-01

    Summary: 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. PMID:27257567

  12. Postural Control and Gait Performance in the Diabetic Peripheral Neuropathy: A Systematic Review.

    PubMed

    Mustapa, Amirah; Justine, Maria; Mohd Mustafah, Nadia; Jamil, Nursuriati; Manaf, Haidzir

    2016-01-01

    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. PMID:27525281

  13. Postural Control and Gait Performance in the Diabetic Peripheral Neuropathy: A Systematic Review

    PubMed Central

    Mustapa, Amirah; Mohd Mustafah, Nadia; Jamil, Nursuriati

    2016-01-01

    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. PMID:27525281

  14. Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy.

    PubMed

    Dong, Han-Yu; Jiang, Xin-Mei; Niu, Chun-Bo; Du, Lin; Feng, Jun-Yan; Jia, Fei-Yong

    2016-01-01

    To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position), prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds), and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus. PMID:26981106

  15. Use of natural compounds in the management of diabetic peripheral neuropathy.

    PubMed

    Galuppo, Maria; Giacoppo, Sabrina; Bramanti, Placido; Mazzon, Emanuela

    2014-01-01

    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. PMID:24603557

  16. Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy

    PubMed Central

    Dong, Han-yu; Jiang, Xin-mei; Niu, Chun-bo; Du, Lin; Feng, Jun-yan; Jia, Fei-yong

    2016-01-01

    To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position), prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds), and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus. PMID:26981106

  17. Treatment of Peripheral Neuropathy in Leprosy: The Case for Nerve Decompression.

    PubMed

    Wan, Eric L; Rivadeneira, Andres F; Jouvin, Renato Martinez; Dellon, A Lee

    2016-03-01

    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. PMID:27257567

  18. Independent Contributions of Alcohol and Stress Axis Hormones to Painful Peripheral Neuropathy

    PubMed Central

    Ferrari, Luiz F.; Levine, Emma; Levine, Jon D.

    2012-01-01

    Painful small-fiber peripheral neuropathy is a debilitating complication of chronic alcohol abuse. Evidence from previous studies suggests that neuroendocrine mechanisms, in combination with other, as yet unidentified actions of alcohol, are required to produce this neuropathic pain syndrome. In addition to neurotoxic effects of alcohol, in the setting of alcohol abuse neuroendocrine stress axes release glucocorticoids and catecholamines. Since receptors for these stress hormones are located on nociceptors, at which they can act to cause neuronal dysfunction, we tested the hypothesis that alcohol and stress hormones act on the nociceptor, independently, to produce neuropathic pain. We used a rat model, which allows the distinction of the effects of alcohol from those produced by neuroendocrine stress axis mediators. We now demonstrate that topical application of alcohol and exposure to unpredictable sound stress, each alone, has no effect on nociceptive threshold. However, when animals that had previous exposure to alcohol were subsequently exposed to stress, they rapidly developed mechanical hyperalgesia. Conversely, sound stress followed by topical alcohol exposure also produced mechanical hyperalgesia. The contribution of stress hormones was prevented by spinal intrathecal administration of oligodeoxynucleotides antisense to β2-adrenergic or glucocorticoid receptor mRNA, which attenuates receptor level in nociceptors, as well as by adrenal medullectomy. These experiments establish an independent role of alcohol and stress hormones on the primary afferent nociceptor in the induction of painful peripheral neuropathy. PMID:23128028

  19. Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: prevalence, risk factors, and fall risk.

    PubMed

    Bao, Ting; Basal, Coby; Seluzicki, Christina; Li, Susan Q; Seidman, Andrew D; Mao, Jun J

    2016-09-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated with chemotherapy, but researchers rarely study its risk factors, fall risk, and prevalence in long-term breast cancer survivors. We aimed to determine CIPN prevalence, risk factors, and association with psychological distress and falls among long-term breast cancer survivors. We conducted Cross-sectional analyses among postmenopausal women with a history of stage I-III breast cancer who received taxane-based chemotherapy. Participants reported neuropathic symptoms of tingling/numbness in hands and/or feet on a 0-10 numerical rating scale. We conducted multivariate logistic regression analyses to evaluate risk factors associated with the presence of CIPN and the relationship between CIPN and anxiety, depression, insomnia, and patient-reported falls. Among 296 participants, 173 (58.4 %) reported CIPN symptoms, 91 (30.7 %) rated their symptoms as mild, and 82 (27.7 %) rated them moderate to severe. Compared with women of normal weight, being obese was associated with increased risk of CIPN (adjusted OR 1.94, 95 % CI: 1.03-3.65). Patients with CIPN reported greater insomnia severity, anxiety, and depression than those without (all p < 0.05). Severity of CIPN was associated with higher rates of falls, with 23.8, 31.9, and 41.5 % in the "no CIPN," "mild," and "moderate-to-severe" groups, respectively, experiencing falls (p = 0.028). The majority of long-term breast cancer survivors who received taxane-based chemotherapy reported CIPN symptoms; obesity was a significant risk factor. Those with CIPN also reported increased psychological distress and falls. Interventions need to target CIPN and comorbid psychological symptoms, and incorporate fall prevention strategies for aging breast cancer survivors. PMID:27510185

  20. Electrophysiologic pattern and prevalence of subclinical peripheral neuropathy in children and adolescents with type I diabetes mellitus in Iran

    PubMed Central

    Toopchizadeh, Vahideh; Shiva, Siamak; Khiabani, Nader-Yousefzadeh; Ghergherechi, Robabeh

    2016-01-01

    Objectives: To evaluate electrophysiologic pattern of subclinical diabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) based on nerve conduction study. Methods: In this cross sectional study, 40 children and adolescents (62.5% female with mean age of 12.73 ± 0.43 years) with T1DM for at least 5 years attending the Pediatrics Clinics. Tabriz University of Medical Sciences, Tabriz, Iran, between 2014 and 2015 were recruited. Demographic and laboratory findings were recorded and all patients underwent clinical neurological examination and electrophysiologic studies. Results: According to electrophysiologic studies, DPN was found in 57.5% of patients including early stage of neuropathy (15%), mild sensory axonal neuropathy (25%), mild sensory motor axonal neuropathy (10%), and moderate sensory motor axonal neuropathy (7.5%). Age, duration of diabetes, fasting blood sugar, and glycosylated hemoglobin levels had no significant difference between patients with and without DPN. Reduced deep tendon reflexes were observed in the upper limb (30%) and lower limb (47.5%) of patients, which were both significantly higher in DPN patients (upper limb [p=0.03] and lower limb [p=0.04]). The most frequent electrophysiologic findings were unobtainable H-reflex, low amplitude sural, and median sensory responses. Conclusion: Subclinical DPN is a common complication found in children and adolescents with TIDM and peripheral sensory axonal neuropathy is the most frequent type. Nerve conduction study is recommended for early detection of DPN and prevention of its progress. PMID:26905353

  1. Effects of Semelil (ANGIPARS™) on diabetic peripheral neuropathy: A randomized, double-blind Placebo-controlled clinical trial

    PubMed Central

    Bakhshayeshi, S.; Madani, SP.; Hemmatabadi, M.; Heshmat, R.; Larijani, B.

    2011-01-01

    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 (ANGIPARS™), a new herbal drug for treatment of diabetic foot ulcers or diabetic peripheral neuropathy. Methods In this double blind clinical trial, 49 type 2 diabetes patients with different degrees of neuropathy were evaluated in two groups (ANGIPARS™ 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. Results Michigan diabetic neuropathy score was decreased notably in ANGIPARS™ group. In the nerve conduction study, appropriate meaningful changes were observed in the distal latency and amplitude in the motor Ulnar nerve in ANGIPARS™ group. Conclusion The results showed limited evidence of efficacy of ANGIPARS™ in diabetic neuropathy treatment and more studies with a larger sample size and longer duration are required. PMID:22615641

  2. Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature

    PubMed Central

    Argyriou, Andreas A; Kyritsis, Athanasios P; Makatsoris, Thomas; Kalofonos, Haralabos P

    2014-01-01

    Commonly used chemotherapeutic agents in oncology/hematology practice, causing toxic peripheral neuropathy, include taxanes, platinum compounds, vinca alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents. This review paper intends to put together and discuss the spectrum of chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to highlight areas of future research to pursue on the topic. Current knowledge shows that the pathogenesis of CIPN still remains elusive, mostly because there are several sites of involvement in the peripheral nervous system. In any case, it is acknowledged that the dorsal root ganglia of the primary sensory neurons are the most common neural targets of CIPN. Both the incidence and severity of CIPN are clinically under- and misreported, and it has been demonstrated that scoring CIPN with common toxicity scales is associated with significant inter-observer variability. Only a proportion of chemotherapy-treated patients develop treatment-emergent and persistent CIPN, and to date it has been impossible to predict high-and low-risk subjects even within groups who receive the same drug regimen. This issue has recently been investigated in the context of pharmacogenetic analyses, but these studies have not implemented a proper methodological approach and their results are inconsistent and not really clinically relevant. As such, a stringent approach has to be implemented to validate that information. Another open issue is that, at present, there is insufficient evidence to support the use of any of the already tested chemoprotective agents to prevent or limit CIPN. The results of comprehensive interventions, including clinical, neurophysiological, and pharmacogenetic approaches, are expected to produce a consistent advantage for both doctors and patients and thus allow the registration and analysis of reliable data on the true characteristics of CIPN, eventually leading to potential preventive and

  3. Development profile in a patient with monosomy 10q and Dup(17p) associated with a peripheral neuropathy

    SciTech Connect

    Pellegrino, J.E.; Spinner, N.B.; Zackai, E.H.

    1996-02-02

    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.

  4. Considerations About Risk Factors for Peripheral Neuropathies in Romanian HIV-Infected Patients

    PubMed Central

    GIUBELAN, L.I.; CUPŞA, A.; DUMITRESCU, FLORENTINA; NICULESCU, IRINA; STOIAN, ANDREEA CRISTINA

    2014-01-01

    Purpose: The study aims at detecting risk factors for developing peripheral neuropathy in Romanian HIV infected subjects. Material/Methods: retrospective study (january 1990-january 2009) who analyzed data from patients hospitalized in the Regional Center Craiova. We have compared 26 patients (group N) diagnosed with peripheral neuropathy  with 40 patients (group C) without neuropsychological sufferings, randomly selected. We have analysed: age, height, HIV mode of transmission, AIDS status, the average and nadir of CD4 lymphocytes, the mean viral load, the average duration of antiretroviral treatment (ART), use and duration of use of d-drugs, the presence of certain coinfection, diabetes or ethanol abuse. Results: the following differences were statistically significant: age (31,54±14,64 vs 23,9±12,03 years, p=0.024), HIV mode of transmission  (parenteral/sexual: 13/13 vs 28/8, p = 0.044), the monitoring time duration (5,31±3,77 vs 7,75±5,4 years, p=0.043), median ART duration (37,2±9,66 vs 45,12±8,75 months, p=0.001). Close to the threshold of statistical significance are the CD4 nadir (97,33±65,6 vs 123,15±43,35 cells/mm3, p=0.058) and duration of use of d–drugs (22,5±31,94 vs 12,24±8,6 months, p=0.057). Odds ratio (OR) and relative risk (RR) increase with age. ROC analysis for the study group establishes a threshold difference of 29 years (sensitivity 50%, specificity 80%). Conclusions: higher age and advanced immunosupression are the most important risk factors for developing symptomatic peripheral neuropathy in Romanian HIV infected patients; taking into account the small number of cases studied, although not statistically significant, it should be noted the CD4 nadir and the length of d-drug use. PMID:24791204

  5. Sensory neuron subpopulation-specific dysregulation of intracellular calcium in a rat model of chemotherapy-induced peripheral neuropathy.

    PubMed

    Yilmaz, E; Gold, M S

    2015-08-01

    The purpose of the present study was to test the prediction that the unique manifestation of chemotherapeutic-induced peripheral neuropathy (CIPN) would be reflected in a specific pattern of changes in the regulation of the intracellular Ca(2+) concentration ([Ca(2+)]i) in subpopulations of cutaneous neurons. To test this prediction, we characterized the pattern of changes in mechanical nociceptive threshold associated with paclitaxel administration (2mg/kg, iv, every other day for four days), as well as the impact of target of innervation and paclitaxel treatment on the regulation of [Ca(2+)]i in subpopulations of putative nociceptive and non-nociceptive neurons. Neurons innervating the glabrous and hairy skin of the hindpaw as well as the thigh were identified with retrograde tracers, and fura-2 was used to assess changes in [Ca(2+)]i. Paclitaxel was associated with a persistent decrease in mechanical nociceptive threshold in response to stimuli applied to the glabrous skin of the hindpaw, but not the hairy skin of the hindpaw or the thigh. However, in both putative nociceptive and non-nociceptive neurons, resting [Ca(2+)]i was significantly lower in neurons innervating the thigh after treatment. The magnitude of the depolarization-evoked Ca(2+) transient was also lower in putative non-nociceptive thigh neurons. More interestingly, while paclitaxel had no detectable influence on either resting or depolarization-evoked Ca(2+) transients in putative non-nociceptive neurons, in putative nociceptive neurons there was a subpopulation-specific decrease in the duration of the evoked Ca(2+) transient that was largely restricted to neurons innervating the glabrous skin. These results suggest that peripheral nerve length alone, does not account for the selective distribution of CIPN symptoms. Rather, they suggest the symptoms of CIPN reflect an interaction between the toxic actions of the therapeutic and unique properties of the neurons deleteriously impacted. PMID

  6. Therapeutic Effects of 15 Hz Pulsed Electromagnetic Field on Diabetic Peripheral Neuropathy in Streptozotocin-Treated Rats

    PubMed Central

    Jiang, Maogang; Li, Feijiang; Cai, Jing; Wu, Xiaoming; Tang, Chi; Xu, Qiaoling; Liu, Juan; Guo, Wei; Shen, Guanghao; Luo, Erping

    2013-01-01

    Although numerous clinical studies have reported that pulsed electromagnetic fields (PEMF) have a neuroprotective role in patients with diabetic peripheral neuropathy (DPN), the application of PEMF for clinic is still controversial. The present study was designed to investigate whether PEMF has therapeutic potential in relieving peripheral neuropathic symptoms in streptozotocin (STZ)-induced diabetic rats. Adult male Sprague–Dawley rats were randomly divided into three weight-matched groups (eight in each group): the non-diabetic control group (Control), diabetes mellitus with 15 Hz PEMF exposure group (DM+PEMF) which were subjected to daily 8-h PEMF exposure for 7 weeks and diabetes mellitus with sham PEMF exposure group (DM). Signs and symptoms of DPN in STZ-treated rats were investigated by using behavioral assays. Meanwhile, ultrastructural examination and immunohistochemical study for vascular endothelial growth factor (VEGF) of sciatic nerve were also performed. During a 7-week experimental observation, we found that PEMF stimulation did not alter hyperglycemia and weight loss in STZ-treated rats with DPN. However, PEMF stimulation attenuated the development of the abnormalities observed in STZ-treated rats with DPN, which were demonstrated by increased hind paw withdrawal threshold to mechanical and thermal stimuli, slighter demyelination and axon enlargement and less VEGF immunostaining of sciatic nerve compared to those of the DM group. The current study demonstrates that treatment with PEMF might prevent the development of abnormalities observed in animal models for DPN. It is suggested that PEMF might have direct corrective effects on injured nerves and would be a potentially promising non-invasive therapeutic tool for the treatment of DPN. PMID:23637830

  7. Clinical and neurophysiological studies of aldose reductase inhibitor ponalrestat in chronic symptomatic diabetic peripheral neuropathy.

    PubMed

    Florkowski, C M; Rowe, B R; Nightingale, S; Harvey, T C; Barnett, A H

    1991-01-01

    Increased flux through the polyol pathway mediated by the enzyme aldose reductase may be associated with the development of diabetic neuropathy. Fifty-four diabetic patients (median age 56 yr, range 25-65 yr) with chronic neuropathic symptoms were randomly allocated to placebo or aldose reductase inhibition (300 or 600 mg ponalrestat ICI 128436) groups for 24 wk. Patients with vibration perception thresholds (VPTs) greater than 35 V at the great toe or thermal difference thresholds (TTs) greater than 10 degrees C on the dorsum of the foot were excluded from the trial. No significant changes were observed in symptoms of pain, numbness, or paresthesia between ponalrestat and placebo groups, and there were no improvements in VPT or TT at several sites. Posterior tibial nerve conduction velocity changed from 35.3 +/- 4.9 m/s at baseline to 33.4 +/- 4.0 m/s at 24 wk (NS) with placebo compared with 37.6 +/- 5.6 vs. 37.2 +/- 8.7 m/s (NS) with 300 mg ponalrestat and 34.5 +/- 6.1 vs. 36.2 +/- 6.8 m/s (NS) with 600 mg ponalrestat. Further studies are indicated with intervention at an earlier stage in the evolution of neuropathy and for longer periods. PMID:1901808

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

    ClinicalTrials.gov

    2016-02-26

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

  9. Patterns and severity of vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia

    PubMed Central

    Smith, Ellen M. Lavoie; Li, Lang; Chiang, ChienWei; Thomas, Karin; Hutchinson, Raymond J.; Wells, Elizabeth M.; Ho, Richard H.; Skiles, Jodi; Chakraborty, Arindom; Bridges, Celia M.; Renbarger, Jamie

    2015-01-01

    Vincristine, a critical component of combination chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL), can lead to vincristine-induced peripheral neuropathy (VIPN). Longitudinal VIPN assessments were obtained over 12 months from newly diagnosed children with ALL (N = 128) aged 1–18 years who received vincristine at one of four academic children’s hospitals. VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS©-PV), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE©), Balis© grading scale, and Pediatric Neuropathic Pain Scale©–Five (PNPS©-5). Of children who provided a full TNS©-PV score, 85/109 (78%) developed VIPN (TNS©-PV ≥4). Mean TNS©-PV, grading scale, and pain scores were low. CTCAE©-derived grades 3 and 4 sensory and motor VIPN occurred in 1.6%/0%, and 1.9%/0% of subjects, respectively. VIPN did not resolve in months 8–12 despite decreasing dose density. VIPN was worse in older children. Partition cluster analysis revealed 2–3 patient clusters; one cluster (n = 14) experienced severe VIPN. In this population, VIPN occurs more commonly than previous research suggests, persists throughout the first year of treatment, and can be severe. PMID:25977177

  10. Institutional Animal Care and Use Committee Considerations for Animal Models of Peripheral Neuropathy

    PubMed Central

    Brabb, Thea; Carbone, Larry; Snyder, Jessica; Phillips, Nona

    2014-01-01

    Peripheral neuropathy and neuropathic pain are debilitating, life-altering conditions that affect a significant proportion of the human population. Animal models, used to study basic disease mechanisms and treatment modalities, are diverse and provide many challenges for institutional animal care and use committee (IACUC) review and postapproval monitoring. Items to consider include regulatory and ethical imperatives in animal models that may be designed to study pain, the basic mechanism of neurodegeneration, and different disease processes for which neuropathic pain is a side effect. Neuropathic pain can be difficult to detect or quantify in many models, and pain management is often unsuccessful in both humans and animals, inspiring the need for more research. Design of humane endpoints requires clear communication of potential adverse outcomes and solutions. Communication with the IACUC, researchers, and veterinary staff is also key for successful postapproval monitoring of these challenging models. PMID:24615447

  11. Global inhibition of reactive oxygen species (ROS) inhibits paclitaxel-induced painful peripheral neuropathy.

    PubMed

    Fidanboylu, Mehmet; Griffiths, Lisa A; Flatters, Sarah J L

    2011-01-01

    Paclitaxel (Taxol®) is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS), the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6), the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN) and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13) completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg) systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day -1 to 12) did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals alone. PMID

  12. Global Inhibition of Reactive Oxygen Species (ROS) Inhibits Paclitaxel-Induced Painful Peripheral Neuropathy

    PubMed Central

    Fidanboylu, Mehmet; Griffiths, Lisa A.; Flatters, Sarah J. L.

    2011-01-01

    Paclitaxel (Taxol®) is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS), the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6), the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN) and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days −1 to 13) completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg) systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day −1 to 12) did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals alone. PMID

  13. Technetium pyrophosphate myocardial uptake and peripheral neuropathy in a rare variant of familial transthyretin (TTR) amyloidosis (Ser23Asn): a case report and literature review.

    PubMed

    Castaño, Adam; Bokhari, Sabahat; Brannagan, Thomas H; Wynn, Julia; Maurer, Mathew S

    2012-03-01

    We report the fourth case of transthyretin amyloidosis (ATTR) Ser23Asn in a 41-year-old Ecuadorian male. He has a pedigree that spans seven generations and involves 24 family members who suffered early cardiac death. Salient presenting symptoms were fatigue, shortness of breath, and peripheral neuropathy. The diagnosis of cardiac amyloid was confirmed by immunohistochemical staining of an endomyocardial biopsy, genotyping and by technetium pyrophosphate ((99m)Tc-PYP) scintigraphy, which remains to be established as a reliable tool to visualize myocardial amyloid involvement in patients with the Ser23Asn transthyretin (TTR) variant. The patient underwent successful combined heart and liver transplant. We add to the current ATTR literature that in patients with the rare Ser23Asn mutation, peripheral nerve in addition to cardiac involvement can occur and (99m)Tc-PYP scintigraphy can be used as an imaging modality to visualize myocardial amyloid. PMID:22149423

  14. Technetium pyrophosphate myocardial uptake and peripheral neuropathy in a rare variant of familial transthyretin (TTR) amyloidosis (Ser23Asn): a case report and literature review

    PubMed Central

    Castaño, Adam; Bokhari, Sabahat; Brannagan, Thomas H.; Wynn, Julia; Maurer, Mathew S.

    2016-01-01

    We report the fourth case of transthyretin amyloidosis (ATTR) Ser23Asn in a 41-year-old Ecuadorian male. He has a pedigree that spans 7 generations and involves 24 family members who suffered early cardiac death. Salient presenting symptoms were fatigue, shortness of breath, and peripheral neuropathy. The diagnosis of cardiac amyloid was confirmed by immunohistochemical staining of an endomyocardial biopsy, genotyping, and by technetium pyrophosphate (99mTc-PYP) scintigraphy, which remains to be established as a reliable tool to visualize myocardial amyloid involvement in patients with the Ser23Asn TTR variant. The patient underwent successful combined heart and liver transplant. We add to the current ATTR literature that in patients with the rare Ser23Asn mutation, peripheral nerve in addition to cardiac involvement can occur and 99mTc-PYP scintigraphy can be used as an imaging modality to visualize myocardial amyloid. PMID:22149423

  15. A rare manifestation of sarcoidosis with sensomotoric neuropathy of the ulnar nerve as the only symptom

    PubMed Central

    Mattiassich, Georg; Schubert, Heinrich; Hutarew, Georg; Wechselberger, Gottfried

    2012-01-01

    A 79-year-old woman was admitted complaining of progressive weakness and numbness of the right hand. The patient was otherwise healthy. The patient's history was unremarkable. Clinical and electrophysiological examination revealed a compression of the ulnar nerve in the ulnar sulcus and in Guyon's canal. Ultrasound evaluation showed a suspicious tumour proximal to the elbow close to the ulnar nerve. The ulnar sulcus was then released and an epineural and perineural lesion 3–4 cm proximal to the sulcus was excised under microscope. The histopathology confirmed the lesion as non-caseating sarcoid granulomas. The patient showed no other signs of systemic sarcoidosis, as neuropathy was the only symptom and the condition improved postoperatively. Sensory deficits and paraesthesia resolved fully. The extension of the minor finger remained slightly inferior compared with the not affected side. Sarcoid neuropathy is a rare neurological complication of sarcoidosis and has to be included in differential diagnosis of nerve conduction impairments. PMID:23192580

  16. A rare manifestation of sarcoidosis with sensomotoric neuropathy of the ulnar nerve as the only symptom.

    PubMed

    Mattiassich, Georg; Schubert, Heinrich; Hutarew, Georg; Wechselberger, Gottfried

    2012-01-01

    A 79-year-old woman was admitted complaining of progressive weakness and numbness of the right hand. The patient was otherwise healthy. The patient's history was unremarkable. Clinical and electrophysiological examination revealed a compression of the ulnar nerve in the ulnar sulcus and in Guyon's canal. Ultrasound evaluation showed a suspicious tumour proximal to the elbow close to the ulnar nerve. The ulnar sulcus was then released and an epineural and perineural lesion 3-4 cm proximal to the sulcus was excised under microscope. The histopathology confirmed the lesion as non-caseating sarcoid granulomas. The patient showed no other signs of systemic sarcoidosis, as neuropathy was the only symptom and the condition improved postoperatively. Sensory deficits and paraesthesia resolved fully. The extension of the minor finger remained slightly inferior compared with the not affected side. Sarcoid neuropathy is a rare neurological complication of sarcoidosis and has to be included in differential diagnosis of nerve conduction impairments. PMID:23192580

  17. [Trigeminus neuropathy as a rare main symptom of progressive systemic sclerosis].

    PubMed

    Brunner, U; Wagenhäuser, F J; Baumgartner, G; Eichmann, A

    1988-02-13

    In addition to the habitual skin manifestations, the following forms of organic involvement were found (with decreasing frequency) in 33 patients with progressive systemic sclerosis treated from 1972-1986 at the Clinic of Rheumatology, University Hospital of Zürich: blood vessels 29, lungs 18, digestive system 11, joints 11, bones 8, lacrimal and salivary glands 7, musculature 3, heart 3, kidneys 2, cranial nerves 1 and peripheral neuropathy 1.-A 65-year-old patient with classic progressive systemic sclerosis and visceral involvement of the esophagus and the lungs showed, as a principal sign, unilateral neuropathy of the trigeminal nerve involving all three branches as well as absent corneal reflex. Electromyographic examination afforded evidence of a sensory neuropathy of the trigeminal nerve. Chemical laboratory tests revealed a typical high titre of antinuclear antibodies. In addition to autoimmunological causes, proliferation of fibrous structures of the perineurium and vascular lesions are discussed in connection with these complications.-The subsequent history of 37 patients with localized scleroderma and 4 patients suffering from progressive systemic sclerosis, treated at the Clinic of Dermatology, University Hospital of Zürich from 1980-1985 provided no evidence of a cranial nerve involvement. The fact that during the period 1975 to 1985 only one patient treated at the Clinic of Neurology of Zürich University Hospital showed signs of disturbances of pupil motility confirms the very rare involvement of the nervous system in progressive systemic sclerosis. PMID:3259011

  18. Peripheral neuropathies in Sjögren's syndrome: a critical update on clinical features and pathogenetic mechanisms.

    PubMed

    Pavlakis, P P; Alexopoulos, H; Kosmidis, M L; Mamali, I; Moutsopoulos, H M; Tzioufas, A G; Dalakas, M C

    2012-08-01

    Sjögren's syndrome is a systemic autoimmune disease that, apart from exocrine glands, may affect every organ or system. Involvement of different sections of the peripheral nervous system results in a wide spectrum of neuropathic manifestations. Based on distinct clinical, electrophysiological and histological criteria, the types of neuropathies seen in Sjögren's syndrome include: a) pure sensory which presents with distal symmetric sensory loss due to axonal degeneration of sensory fibers; sensory ataxia due to loss of proprioceptive large fibers (ganglionopathy); or with painful dysethesias (small fiber sensory neuropathy) due to degeneration of cutaneous axons. The latter appears to be the most common neuropathy in Sjögren's syndrome and requires skin biopsy for diagnosis to document loss or reduction of nerve fiber density; b) sensorimotor polyneuropathy affecting sensory and motor axons, often associated with severe systemic or pro-lymhomatous manifestations, such as palpable purpura and cryoglobulinemia, and c) rare types that include autoimmune demyelinating neuropathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy. In this review, the frequency, prevalence and diagnostic criteria for each neuropathy subset are discussed and possible pathogenetic mechanisms are outlined. PMID:22318209

  19. Improvement of cutaneous sensitivity in diabetic peripheral neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate.

    PubMed

    Walker, Mackie J; Morris, Lauren M; Cheng, Dunlei

    2010-01-01

    Studies of monotherapy with L-methylfolate, methylcobalamin, or pyridoxal 5'-phosphate suggest that these B vitamins may reverse both the symptoms and the pathophysiology of diabetic peripheral neuropathy (DPN). The efficacy of oral-combination L-methylfolate, 3 mg; methylcobalamin, 2 mg; and pyridoxal 5'-phosphate, 35 mg (LMF-MC-PP) in restoring cutaneous sensitivity in patients with type 2 diabetes with DPN was evaluated in 20 type 2 diabetic patients who were given LMF-MC-PP twice daily for 4 weeks and then once daily for an additional 48 weeks. Statistically significant improvement in 1-point (tactile) and 2-point (discriminatory) static testing at the right and left great toe and heel in the patients was observed in all 3 follow-up periods: 1) baseline to 6 months, 2) baseline to 1 year, and 3) 6 months to 1 year. The greatest improvement occurred between baseline and 1 year of treatment. Treatment with oral LMF-MC-PP appears to promote restoration of lost cutaneous sensation in DPN. PMID:21206429

  20. Clinical, Electrodiagnostic, and Genetic Features of Tangier Disease in an Adolescent Girl with Presentation of Peripheral Neuropathy.

    PubMed

    Per, Huseyin; Canpolat, Mehmet; Bayram, Ayşe Kaçar; Ulgen, Ege; Baran, Burçin; Kardas, Fatih; Gumus, Hakan; Kumandas, Sefer; Bilguvar, Kaya; Çağlayan, Ahmet Okay

    2015-12-01

    Tangier disease (TD) is a rare, autosomal recessive inherited disorder caused by a mutation in the adenosine triphosphate-binding cassette transporter 1 (ABCA1) gene, which results in a decrease in plasma high-density lipoprotein (HDL) levels. Peripheral neuropathy can be seen in approximately 50% of patients with TD, which usually occurs after the age of 15 years, and is characterized by relapsing-remitting mono- or polyneuropathy or syringomyelia-like neuropathy. Herein, we report a 16-year-old female patient who was initially diagnosed with peripheral neuropathy at the age of 13 years. Whole exome sequencing was performed, and a nonsense mutation (p.Arg1817X) in ABCA1 was identified. The patient was investigated for systemic findings of TD after the genetic diagnosis was made, and low (< 5 mg/dL) levels of HDL cholesterol were detected by lipid electrophoresis. Other family members were reexamined after the diagnosis of the proband, and asymptomatic sister of the proband was diagnosed with TD. We would like to emphasize that TD should be considered in the differential diagnosis of pediatric patients presenting with peripheral neuropathy; furthermore detection of HDL levels by lipid electrophoresis is a simple but indicative diagnostic test. PMID:26479764

  1. Prevention of chemotherapy-induced peripheral neuropathy by the small-molecule inhibitor pifithrin-μ.

    PubMed

    Krukowski, Karen; Nijboer, Cora H; Huo, XiaoJiao; Kavelaars, Annemieke; Heijnen, Cobi J

    2015-11-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. It is the most frequent cause of dose reduction or treatment discontinuation in patients treated for cancer with commonly used drugs including taxanes and platinum-based compounds. No FDA-approved treatments for CIPN are available. In rodents, CIPN is represented by peripheral mechanical allodynia in association with retraction of intraepidermal nerve fibers. The mechanism of chemotherapy-induced neurotoxicity is unclear, but it has been established that mitochondrial dysfunction is an important component of the dysregulation in peripheral sensory neurons. We have shown earlier that inhibition of mitochondrial p53 accumulation with the small compound pifithrin-μ (PFT-μ) prevents cerebral neuronal death in a rodent model of hypoxic-ischemic brain damage. We now explore whether PFT-μ is capable of preventing neuronal mitochondrial damage and CIPN in mice. We demonstrate for the first time that PFT-μ prevents both paclitaxel- and cisplatin-induced mechanical allodynia. Electron microscopic analysis of peripheral sensory nerves revealed that PFT-μ secured mitochondrial integrity in paclitaxel-treated mice. In addition, PFT-μ administration protects against chemotherapy-induced loss of intraepidermal nerve fibers in the paw. To determine whether neuroprotective treatment with PFT-μ would interfere with the antitumor effects of chemotherapy, ovarian tumor cells were cultured in vitro with PFT-μ and paclitaxel. Pifithrin-μ does not inhibit tumor cell death but even enhances paclitaxel-induced tumor cell death. These data are the first to identify PFT-μ as a potential therapeutic strategy for prevention of CIPN to combat one of the most devastating side effects of chemotherapy. PMID:26473292

  2. Serum Phosphorylated Neurofilament-Heavy Chain, a Potential Biomarker, is Associated With Peripheral Neuropathy in Patients With Type 2 Diabetes

    PubMed Central

    Qiao, Xiaona; Zhang, Shuo; Zhao, Weiwei; Ye, Hongying; Yang, Yehong; Zhang, Zhaoyun; Miao, Qing; Hu, Renming; Li, Yiming; Lu, Bin

    2015-01-01

    Abstract 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. PMID:26554790

  3. Value of Nerve Biopsy in Patients With Latent Malignant Hemopathy and Peripheral Neuropathy

    PubMed Central

    Duchesne, Mathilde; Mathis, Stéphane; Corcia, Philippe; Richard, Laurence; Ghorab, Karima; Jaccard, Arnaud; Magy, Laurent; Vallat, Jean-Michel

    2015-01-01

    Abstract Hematological malignancies include several diseases that may affect the peripheral nervous system (PNS) through various mechanisms. A common and challenging situation is represented by the occurrence of an active peripheral neuropathy in a patient with a supposed inactive hematological disorder. We report clinical, electrophysiological, biological, and pathological data of 8 patients with latent malignant hemopathies (most were considered in remission): B-cell chronic lymphocytic leukemia in 3 patients, B-cell lymphoma in 1 patient, low-grade non-Hodgkin's lymphoma in 1 patient, Waldenström's macroglobulinemia in 1 patient, smoldering multiple myeloma in 1 patient, and monoclonal gammopathy of undetermined significance in 1 patient. In all these cases, the nerve biopsy (NB) helped to diagnose the hematological relapse or detect a pathological mechanism linked to the hematological disorder: epineurial lymphocytic infiltration in 5 patients (including one with antimyelin-associated glycoprotein antibodies), cryoglobulin deposits in 1 patient, chronic inflammatory demyelinating polyneuropathy in 1 patient, and necrotizing vasculitis in 1 patient. In each case, pathological findings were crucial to select the adequate treatment, leading to an improvement in the neurological and biological manifestations. These observations illustrate the value of NB and the need for active collaboration between neurologists and hematologists in such cases. PMID:25621682

  4. Peripheral motor neuropathy is associated with defective kinase regulation of the KCC3 cotransporter.

    PubMed

    Kahle, Kristopher T; Flores, Bianca; Bharucha-Goebel, Diana; Zhang, Jinwei; Donkervoort, Sandra; Hegde, Madhuri; Hussain, Gulnaz; Duran, Daniel; Liang, Bo; Sun, Dandan; Bönnemann, Carsten G; Delpire, Eric

    2016-01-01

    Using exome sequencing, we identified a de novo mutation (c.2971A>G; T991A) in SLC12A6, the gene encoding the K(+)-Cl(-) cotransporter KCC3, in a patient with an early-onset, progressive, and severe peripheral neuropathy primarily affecting motor neurons. Normally, the WNK kinase-dependent phosphorylation of T(991) tonically inhibits KCC3; however, cell swelling triggers Thr(991) dephosphorylation to activate the transporter and restore cell volume. KCC3 T991A mutation in patient cells abolished Thr(991) phosphorylation, resulted in constitutive KCC3 activity, and compromised cell volume homeostasis. KCC3(T991A/T991A) mutant mice exhibited constitutive KCC3 activity and recapitulated aspects of the clinical, electrophysiological, and histopathological findings of the patient. These results suggest that the function of the peripheral nervous system depends on finely tuned, kinase-regulated KCC3 activity and implicate abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration. PMID:27485015

  5. Mice lacking glutamate carboxypeptidase II are protected from peripheral neuropathy and ischemic brain injury.

    PubMed

    Bacich, Dean J; Wozniak, Krystyna M; Lu, X-C May; O'Keefe, Denize S; Callizot, Noelle; Heston, Warren D W; Slusher, Barbara S

    2005-10-01

    Excessive glutamate release is associated with neuronal damage. A new strategy for the treatment of neuronal injury involves inhibition of the neuropeptidase glutamate carboxypeptidase II (GCP II), also known as N-acetylated alpha-linked acidic dipeptidase. GCP II is believed to mediate the hydrolysis of N-acetyl-aspartyl-glutamate (NAAG) to glutamate and N-acetyl-aspartate, and inhibition of NAAG peptidase activity (by GCP II and other peptidases) is neuroprotective. Mice were generated in which the Folh1 gene encoding GCP II was disrupted (Folh1-/- mice). No overt behavioral differences were apparent between Folh1-/- mice and wild-type littermates, with respect to their overall performance in locomotion, coordination, pain threshold, cognition and psychiatric behavioral paradigms. Morphological analysis of peripheral nerves, however, showed significantly smaller axons (reduced myelin sheaths and axon diameters) in sciatic nerves from Folh1-/- mice. Following sciatic nerve crush, Folh1-/- mice suffered less injury and recovered faster than wild-type littermates. In a model of ischemic injury, the Folh1-/- mice exhibited a significant reduction (p < 0.05) in infarct volume compared with their wild-type littermates when subjected to middle cerebral artery occlusion, a model of stroke. These findings support the hypothesis that GCP II inhibitors may represent a novel treatment for peripheral neuropathies as well as stroke. PMID:16190866

  6. Thymoquinone Alleviates the Experimental Diabetic Peripheral Neuropathy by Modulation of Inflammation

    PubMed Central

    Chen, Long; Li, Bing; Chen, Biqin; Shao, Yiye; Luo, Qiong; Shi, Xiaohong; Chen, Yinghui

    2016-01-01

    Thymoquinone has been reported to exhibit antioxidant and anti-inflammatory effects. Inflammation plays an important role in pathogenesis of diabetic peripheral neuropathy. This study investigated the effects of TQ on proliferation and apoptosis of Schwann cells exposed to high glucose conditions and electrophysiological and morphological changes of the sciatic nerve in a DPN rat model as well as relevant inflammatory mechanism. Cell proliferation and apoptosis of Schwann cells were measured using the Cell Counting Kit-8 and flow cytometry. DPN model was established in streptozotocin-induced diabetic rats. Nerve conduction velocity was measured before and after treatment. Morphologic changes were observed by H&E staining and transmission electron microscopy. COX-2, IL-1β, IL-6, and Caspase-3 expression was investigated by western blotting and Bio-Plex ProTM Assays. Finally, TQ alleviated the inhibition of Schwann cell proliferation and protected against Schwann cell apoptosis. It improved nerve conduction velocity, and alleviated the DPN-induced morphological changes and demyelination of the sciatic nerve. COX-2, IL-1β, IL-6 and Caspase-3 expression in sciatic nerve or isolated cultured Schwann cells, were also decreased by TQ. These results indicate TQ has a protective effect on peripheral nerves in a DPN rat model. The mechanism may be mediated partly by the modulation of the inflammatory reaction. PMID:27545310

  7. Thymoquinone Alleviates the Experimental Diabetic Peripheral Neuropathy by Modulation of Inflammation.

    PubMed

    Chen, Long; Li, Bing; Chen, Biqin; Shao, Yiye; Luo, Qiong; Shi, Xiaohong; Chen, Yinghui

    2016-01-01

    Thymoquinone has been reported to exhibit antioxidant and anti-inflammatory effects. Inflammation plays an important role in pathogenesis of diabetic peripheral neuropathy. This study investigated the effects of TQ on proliferation and apoptosis of Schwann cells exposed to high glucose conditions and electrophysiological and morphological changes of the sciatic nerve in a DPN rat model as well as relevant inflammatory mechanism. Cell proliferation and apoptosis of Schwann cells were measured using the Cell Counting Kit-8 and flow cytometry. DPN model was established in streptozotocin-induced diabetic rats. Nerve conduction velocity was measured before and after treatment. Morphologic changes were observed by H&E staining and transmission electron microscopy. COX-2, IL-1β, IL-6, and Caspase-3 expression was investigated by western blotting and Bio-Plex Pro(TM) Assays. Finally, TQ alleviated the inhibition of Schwann cell proliferation and protected against Schwann cell apoptosis. It improved nerve conduction velocity, and alleviated the DPN-induced morphological changes and demyelination of the sciatic nerve. COX-2, IL-1β, IL-6 and Caspase-3 expression in sciatic nerve or isolated cultured Schwann cells, were also decreased by TQ. These results indicate TQ has a protective effect on peripheral nerves in a DPN rat model. The mechanism may be mediated partly by the modulation of the inflammatory reaction. PMID:27545310

  8. Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy

    PubMed Central

    Ferdousi, Maryam; Azmi, Shazli; Petropoulos, Ioannis Nikolaos; Fadavi, Hassan; Ponirakis, Georgios; Marshall, Andrew; Tavakoli, Mitra; Malik, Imaan; Mansoor, Wasat; Malik, Rayaz Ahmed

    2015-01-01

    There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration. PMID:26430773

  9. The influence of diabetic peripheral neuropathy on local postural muscle and central sensory feedback balance control.

    PubMed

    Toosizadeh, Nima; Mohler, Jane; Armstrong, David G; Talal, Talal K; Najafi, Bijan

    2015-01-01

    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, P<0.01), which suggests a compromised local-control 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, P<0.02), which suggests an adaptation mechanism to reduce the overall body sway in DPN patients. Interestingly, significant negative correlations were observed between central-control rate of sway with neuropathy severity (rPearson = 0.65-085, P<0.05) and the history of diabetes (rPearson = 0.58-071, P<0.05). Results suggest that in the lack of sensory feedback cueing, DPN participants were highly unstable compared to controls. 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

  10. The Influence of Diabetic Peripheral Neuropathy on Local Postural Muscle and Central Sensory Feedback Balance Control

    PubMed Central

    2015-01-01

    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, P<0.01), which suggests a compromised local-control 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, P<0.02), which suggests an adaptation mechanism to reduce the overall body sway in DPN patients. Interestingly, significant negative correlations were observed between central-control rate of sway with neuropathy severity (rPearson = 0.65-085, P<0.05) and the history of diabetes (rPearson = 0.58-071, P<0.05). Results suggest that in the lack of sensory feedback cueing, DPN participants were highly unstable compared to controls. 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

  11. Amelioration of Cisplatin-Induced Experimental Peripheral Neuropathy by a Small Molecule Targeting p75NTR

    PubMed Central

    Friesland, Amy; Weng, Zhiying; Duenas, Maria; Massa, Stephen M.; Longo, Frank M.; Lu, Qun

    2014-01-01

    Cisplatin is an effective and widely used first-line chemotherapeutic drug for treating cancers. However, many patients sustain cisplatin-induced peripheral neuropathy (CIPN), often leading to a reduction in drug dosages or complete cessation of treatment altogether. Therefore, it is important to understand cisplatin mechanisms in peripheral nerve tissue mediating its toxicity and identify signaling pathways for potential intervention. Rho GTPase activation is increased following trauma in several models of neuronal injury. Thus, we investigated whether components of the Rho signaling pathway represent important neuroprotective targets with the potential to ameliorate CIPN and thereby optimize current chemotherapy treatment regimens. We have developed a novel CIPN model in the mouse. Using this model and primary neuronal culture, we determined whether LM11A-31, a small-molecule, orally bioavailable ligand of the p75 neurotrophin receptor (p75NTR), can modulate Rho GTPase signaling and reduce CIPN. Von Frey filament analysis of sural nerve function showed that LM11A-31 treatment prevented decreases in peripheral nerve sensation seen with cisplatin treatment. Morphometric analysis of harvested sural nerves revealed that cisplatin-induced abnormal nerve fiber morphology and the decreases in fiber area were alleviated with concurrent LM11A-31 treatment. Cisplatin treatment increased RhoA activity accompanied by the reduced tyrosine phosphorylation of SHP-2, which was reversed by LM11A-31. LM11A-31 also countered the effects of calpeptin, which activated RhoA by inhibiting SHP-2 tyrosine phosphatase. Therefore, suppression of RhoA signaling by LM11A-31 that blocks proNGF binding to p75NTR or activates SHP-2 tyrosine phosphatase downstream of NGF receptor enhances neuroprotection in experimental CIPN in mouse model. PMID:25277379

  12. Prolonged Oxaliplatin Exposure Alters Intracellular Calcium Signaling: A New Mechanism To Explain Oxaliplatin-Associated Peripheral Neuropathy

    PubMed Central

    Schulze, Christin; McGowan, Margit; Jordt, Sven; Ehrlich, Barbara E

    2012-01-01

    Oxaliplatin is a platinum based cytotoxic agent commonly used to treat colorectal cancers. Despite its effectiveness, oxaliplatin administration is associated with the development of cold-induced peripheral neuropathy. This potentially permanent side effect is provoked by cold exposure and can range from mild and self limited to severe and debilitating. Even with tumor shrinkage, these painful side effects can force dose-reduction or discontinuation of treatment. Neither the mechanism of action of oxaliplatin nor that of cold-induced neuropathy is understood. Paclitaxel, an entirely different chemotherapeutic agent used to treat a variety of malignancies, also is associated with the development of peripheral neuropathy. Unlike oxaliplatin, neurotoxicity arising from paclitaxel treatment is better understood and was found to have profound effects on intracellular calcium signaling (1,2). In this study we examined the effects of oxaliplatin on calcium signaling pathways and found that acute exposure of either a neuroblastoma cell line or primary neurons with therapeutic concentrations of oxaliplatin had no effect on intracellular calcium signaling. We also found that cellular temperature sensors (TRP channels) were also not activated by oxaliplatin. Interestingly, prolonged exposure of oxaliplatin sensitized cells to subsequent stimuli and enhanced the magnitude of intracellular calcium responses. Taken together, our results suggest that acute oxaliplatin exposure will not induce abnormal calcium signaling but oxaliplatin-primed cells do exhibit enhanced sensitivity. These findings provide new insight to the mechanism behind oxaliplatin-induced neuropathy. PMID:21859566

  13. Assessing the Quality of Reports about Randomized Controlled Trials of Acupuncture Treatment on Diabetic Peripheral Neuropathy

    PubMed Central

    Yi, Guo; Zelin, Chen; Yang, Bai; Zixu, Wang; Yajun, Wang

    2012-01-01

    Background To evaluate the reports’ qualities which are about randomized controlled trials (RCTs) of acupuncture treatment on Diabetic Peripheral Neuropathy (DPN). Methodology/Principal Findings Eight databases including The Cochrane Library(1993–Sept.,2011), PubMed (1980–Sept., 2011), EMbase (1980–Sept.,2011), SCI Expanded (1998–Sept.,2011), China Biomedicine Database Disc (CBMdisc, 1978–Sept., 2011), China National Knowledge Infrastructure (CNKI, 1979–Sept., 2011 ), VIP (a full text issues database of China, 1989–Sept., 2011), Wan Fang (another full text issues database of China 1998–Sept., 2011) were searched systematically. Hand search for further references was conducted. Language was limited to Chinese and English. We identified 75 RCTs that used acupuncture as an intervention and assessed the quality of these reports with the Consolidated Standards for Reporting of Trials statement 2010 (CONSORT2010) and Standards for Reporting Interventions Controlled Trials of Acupuncture 2010(STRICTA2010). 24 articles (32%) applied the method of random allocation of sequences. No article gave the description of the mechanism of allocation concealment, no experiment applied the method of blinding. Only one article (1.47%) could be identified directly from its title as about the Randomized Controlled Trials, and only 4 articles gave description of the experimental design. No article mentioned the number of cases lost or eliminated. During one experiment, acupuncture syncope led to temporal interruption of the therapy. Two articles (2.94%) recorded the number of needles, and 8 articles (11.76%) mentioned the depth of needle insertion. None of articles reported the base of calculation of sample size, or has any analysis about the metaphase of an experiment or an explanation of its interruption. One (1.47%) mentioned intentional analysis (ITT). Conclusions/Significance The quality of the reports on RCTs of acupuncture for Diabetic Peripheral Neuropathy is

  14. The role of miR-146a in dorsal root ganglia neurons of experimental diabetic peripheral neuropathy.

    PubMed

    Wang, L; Chopp, M; Szalad, A; Zhang, Y; Wang, X; Zhang, R L; Liu, X S; Jia, L; Zhang, Z G

    2014-02-14

    Sensory neurons mediate diabetic peripheral neuropathy. Using a mouse model of diabetic peripheral neuropathy (BKS.Cg-m+/+Lepr(db)/J (db/db) mice) and cultured dorsal root ganglion (DRG) neurons, the present study showed that hyperglycemia downregulated miR-146a expression and elevated interleukin-1 receptor-activated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) levels in DRG neurons. In vitro, elevation of miR-146a by miR-146a mimics in DRG neurons increased neuronal survival under high-glucose conditions. Downregulation and elevation of miR-146a in DRG neurons, respectively, were inversely related to IRAK1 and TRAF6 levels. Treatment of diabetic peripheral neuropathy with sildenafil, a phosphodiesterase type 5 inhibitor, augmented miR-146a expression and decreased levels of IRAK1 and TRAF6 in the DRG neurons. In vitro, blockage of miR-146a in DRG neurons abolished the effect of sildenafil on DRG neuron protection and downregulation of IRAK1 and TRAF6 proteins under hyperglycemia. Our data provide the first evidence showing that miR-146a plays an important role in mediating DRG neuron apoptosis under hyperglycemic conditions. PMID:24316060

  15. CX3CR1-Mediated Akt1 Activation Contributes to the Paclitaxel-Induced Painful Peripheral Neuropathy in Rats.

    PubMed

    Li, Dai; Chen, Hui; Luo, Xiao-Huan; Sun, Yang; Xia, Wei; Xiong, Yuan-Chang

    2016-06-01

    Painful peripheral neuropathy is a serious dose-limiting side effect of paclitaxel therapy, which unfortunately often happens during the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms of the painful peripheral neuropathy remain largely unknown. Here, we found that paclitaxel treatment (3 × 8 mg/kg, cumulative dose 24 mg/kg) upregulated the expression of CX3CR1 and phosphorylated Akt1 in DRG and spinal dorsal horn. Blocking of Akt1 pathway activation with different inhibitor (MK-2206 or LY294002) significantly attenuated mechanical allodynia and thermal hyperalgesia induced by paclitaxel. Furthermore, inhibition of CX3CR1 by using neutralizing antibody not only prevented Akt1 activation in DRG and spinal dorsal horn but also alleviated pain-related behavior induced by paclitaxel treatment. This study suggested that CX3CR1/Akt1 signaling pathway may be a potential target for prevention and reversion of the painful peripheral neuropathy induced by paclitaxel. PMID:26961886

  16. Prevention of oxaliplatin-induced peripheral neuropathy by a polyamine-reduced diet—NEUROXAPOL: protocol of a prospective, randomised, controlled, single-blind and monocentric trial

    PubMed Central

    Balayssac, David; Ferrier, Jérémy; Pereira, Bruno; Gillet, Brigitte; Pétorin, Caroline; Vein, Julie; Libert, Frédéric; Eschalier, Alain; Pezet, Denis

    2015-01-01

    Introduction Oxaliplatin remains the most widely used chemotherapeutic agent for treating advanced colorectal cancer but its efficacy is hampered by dose-limiting neurotoxicity manifested by a painful polyneuropathy. Oxaliplatin-induced peripheral neuropathy (OIPN) is characterised by acute and transient cold hyperaesthesia in the hours and days following oxaliplatin infusion (>90% of patients), but also by retarded chronic neuropathy due to the repetition of chemotherapy cycles (30–50% of patients). OIPN impairs the health-related quality of life (HRQOL) of patients and no preventive or curative strategies have as yet proven effective. A polyamine-reduced diet (PRD) has recently demonstrated its efficacy to prevent OIPN in animals without adverse effects. Methods and analysis The NEUROXAPOL trial is a prospective, randomised, controlled, single-blind, monocentric and interventional study. This trial is aimed at evaluating the efficacy and feasibility of a PRD compared to a normal polyamine containing diet to prevent OIPN in patients treated by oxaliplatin-based chemotherapy. Patients (n=40 per group) will be randomly assigned to receive either a PRD or a normal diet before and during the chemotherapy regimen. The main objectives are to improve the cold pain thresholds, neuropathic pain symptoms, comorbidities (anxiety and depression) and HRQOL of patients. The primary end point is the assessment of cold pain thresholds 2 weeks after the third cycle of chemotherapy. The secondary end points are the evaluation of thermal pain thresholds, the grade of neuropathy, neuropathic pain, symptoms of anxiety and depression and HRQOL, until the 12th cycle of chemotherapy. Ethics and dissemination The study was approved by an independent medical ethics committee 1 (CPP Sud Est 1, Saint Etienne, France) and registered by the competent French authority (ANSM, Saint Denis, France). The results will be disseminated in a peer-reviewed journal and presented at international

  17. Tang-Tong-Fang Confers Protection against Experimental Diabetic Peripheral Neuropathy by Reducing Inflammation

    PubMed Central

    Li, Mingdi; Huang, Da; Liu, Xiaoxing; Lin, Lan

    2015-01-01

    Tang-tong-fang (TTF) is a Chinese herbal formula that has been shown to be beneficial in diabetic peripheral neuropathy (DPN), a common complication secondary to diabetic microvascular injury. However, the underlying mechanism of protection in nerve ischemia provided by TTF is still unclear. We hypothesized that TTF alleviates DPN via inhibition of ICAM-1 expression. Therefore, we tested the effect of TTF in a previously established DPN model, in which nerve injury was induced by ischemia/reperfusion in streptozotocin-induced diabetic rats. We found that the conduction velocity and amplitude of action potentials of sciatic nerve conduction were reduced in the DPN model group but were rescued by TTF treatment. In addition, TTF treatment also attenuated the effect of DPN on other parameters including histology and ultrastructural changes, expression of ICAM-1, MPO, and TNF-α in rat sciatic nerves, and plasma sICAM-1 and MPO levels. Together, our data suggest that TTF treatment may alleviate DPN via ICAM-1 inhibition. PMID:26539228

  18. Natural products and complementary therapies for chemotherapy-induced peripheral neuropathy: A systematic review.

    PubMed

    Brami, Cloé; Bao, Ting; Deng, Gary

    2016-02-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side-effect without any FDA-approved treatment option. Prior reviews focus mostly on pharmacological interventions, but nonpharmaceutical interventions have also been evaluated. A Web of Science and PubMed database search to identify relevant RCTs from January 2005 to May 2015 included the terms: CIPN, cancer; and supplements, vitamin E, goshajinkigan, kampo, acetyl-L-carnitine, carnitine, alpha-lipoic acid, omega-3, glutamine, or glutamate; or massage, acupuncture, mind-body practice, yoga, meditation, Tai-Chi, physical activity, or exercise. Of 1465 publications screened, 12 RCTs evaluated natural products and one evaluated electroacupuncture. Vitamin E may help prevent CIPN. L-Glutamine, goshajinkigan, and omega-3 are also promising. Acetyl-L-carnitine may worsen CIPN and alpha-lipoic acid activity is unknown. Electroacupuncture was not superior to placebo. No RCTs were published regarding other complementary therapies, although some studies mention positive incidental findings. Natural products and complementary therapies deserve further investigation, given the lack of effective CIPN interventions. PMID:26652982

  19. Peripheral neuropathy reduces asymmetries in inter-limb transfer in a visuo-motor task.

    PubMed

    Pan, Zhujun; Van Gemmert, Arend W A

    2016-05-01

    Asymmetry of inter-limb transfer has been associated with the specialization of the dominant and non-dominant motor system. Reductions of asymmetry have been interpreted as behavioural evidence showing a decline of hemispheric lateralization. A previous study showed that ageing did not qualitatively change the inter-limb transfer asymmetry of a visuo-motor task. The current study elaborates on these findings; it examines whether diminished somatosensory information as a result of peripheral neuropathy (PN) adversely affects inter-limb transfer asymmetry. Twenty individuals affected by PN and 20 older controls were recruited and divided equally across two groups. One group trained a visuo-motor task with the right hand while the other group trained it with the left hand. Performance (initial direction error) of the untrained hand before and after training was collected to determine learning effects from inter-limb transfer. Similar to previous studies, the current study showed asymmetric inter-limb transfer in older controls. In contrast, PN showed inter-limb transfer in both directions indicating that PN reduces inter-limb transfer asymmetry. Increased bilateral hemispheric recruitment is suggested to be responsible for this reduced asymmetry which may compensate for deteriorated tactile and/or proprioceptive inputs in PN. Two possible hypotheses are discussed explaining the relationship between declined somatosensory information and increases in bilateral hemispheric recruitment. PMID:26857239

  20. Metanx alleviates multiple manifestations of peripheral neuropathy and increases intraepidermal nerve fiber density in Zucker diabetic fatty rats.

    PubMed

    Shevalye, Hanna; Watcho, Pierre; Stavniichuk, Roman; Dyukova, Elena; Lupachyk, Sergey; Obrosova, Irina G

    2012-08-01

    Metanx is a product containing L-methylfolate, pyridoxal 5'-phosphate, and methylcobalamin for management of endothelial dysfunction. Metanx ingredients counteract endothelial nitric oxide synthase uncoupling and oxidative stress in vascular endothelium and peripheral nerve. This study evaluates Metanx on diabetic peripheral neuropathy in ZDF rats, a model of type 2 diabetes. Metanx was administered to 15-week-old ZDF and ZDF lean rats at either 4.87 mg ⋅ kg(-1) ⋅ day(-1) (a body weight-based equivalent of human dose) or 24.35 mg ⋅ kg(-1) ⋅ day(-1) by oral gavage two times a day for 4 weeks. Both doses alleviated hind limb digital sensory, but not sciatic motor, nerve conduction slowing and thermal and mechanical hypoalgesia in the absence of any reduction of hyperglycemia. Low-dose Metanx increased intraepidermal nerve fiber density but did not prevent morphometric changes in distal tibial nerve myelinated fibers. Metanx treatment counteracted endothelial nitric oxide synthase uncoupling, inducible nitric oxide synthase upregulation, and methylglyoxal-derived advanced glycation end product, nitrotyrosine, and nitrite/nitrate accumulation in the peripheral nerve. In conclusion, Metanx, at a body weight-based equivalent of human dose, increased intraepidermal nerve fiber density and improved multiple parameters of peripheral nerve function in ZDF rats. Clinical studies are needed to determine if Metanx finds use in management of diabetic peripheral neuropathy. PMID:22751692

  1. Prevalence and correlates of diabetic peripheral neuropathy in a Saudi Arabic population: a cross-sectional study.

    PubMed

    Wang, Dong D; Bakhotmah, Balkees A; Hu, Frank B; Alzahrani, Hasan Ali

    2014-01-01

    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. PMID:25184511

  2. Chinese Herbal Medicine for Diabetic Peripheral Neuropathy: An Updated Meta-Analysis of 10 High-Quality Randomized Controlled Studies

    PubMed Central

    Hao, Chi-zi; Wu, Fan; Lu, Lin; Wang, Juan; Guo, Yi; Liu, Ai-ju; Liao, Wei-jing; Zheng, Guo-qing

    2013-01-01

    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. PMID:24146822

  3. Efficacy and safety of prostaglandin E1 plus lipoic acid combination therapy versus monotherapy for patients with diabetic peripheral neuropathy.

    PubMed

    Jiang, De-Qi; Li, Ming-Xing; Ma, Yan-Jiao; Wang, Yan; Wang, Yong

    2016-05-01

    The aim of this report was to evaluate the efficacy and safety of prostaglandin E1 (PGE1) plus lipoic acid (LA) for the treatment of diabetic peripheral neuropathy (DPN) compared with that of PGE1 or LA monotherapy. Randomized controlled trials (RCT) published up to 3 August 2014 were reviewed. A random or fixed effect model was used to analyze outcomes expressed as risk ratios (RR) or mean difference (MD) with a 95% confidence interval (CI). I(2) statistic was used to assess heterogeneity. Subgroup and sensitivity analyses were performed. The outcomes measured were as follows: clinical efficacy, median motor nerve conduction velocity (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV and adverse effects. Thirty-one RCT with 2676 participants were included. Clinical efficacy of PGE1+LA combination therapy was significantly better than monotherapy (p<0.00001, RR=1.32, 95% CI 1.26 to 1.38). Compared with monotherapy, PGE1+LA combination therapy led to significant improvements in median MNCV (p<0.00001, MD=4.69, 95% CI 3.16 to 6.23), median SNCV (p<0.00001, MD=5.46, 95% CI 4.04 to 6.88), peroneal MNCV (p<0.00001, MD=5.19, 95% CI 3.71 to 6.67) and peroneal SNCV (p<0.00001, MD=5.50, 95% CI 3.30 to 7.70). There were no serious adverse events associated with drug intervention. PGE1+LA combination therapy is superior to PGE1 or LA monotherapy for improvement of neuropathic symptoms and nerve conduction velocities in patients with DPN. These findings should be further validated by larger well-designed and high-quality RCT. PMID:26775115

  4. Gait characteristics of people with diabetes-related peripheral neuropathy, with and without a history of ulceration.

    PubMed

    Raspovic, Anita

    2013-09-01

    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%: p<0.01); ankles (sagittal plane, 22%: p<0.01) and first metatarsophalangeal joints (sagittal plane, 32%: p=0.01), with less foot rotation (24%: p=0.04). Kinetic alterations in DNU included lower: ankle maximum power (21%: p=0.03) and vertical ground reaction force 2nd peak (6%: p<0.01). The study findings identified gait alterations in people with clinically severe peripheral neuropathy and related plantar foot ulcer history. Further research is needed to explore potential casual pathways. PMID:23583607

  5. Immunohistochemical Detection of HCV in Nerves and Muscles of Patients with HCV Associated Peripheral Neuropathy and Myositis

    PubMed Central

    Younis, Layla K.; Talaat, Farouk M; Deif, Ahmed H; Borei, Mohamed F; Reheim, Seham M Abdel; El Salmawy, Doa H

    2007-01-01

    Background : Chronic hepatitis C Virus (HCV) infection may be associated with numerous extrahepatic manifestations, such as mixed cryoglobulinaemia, membranoproliferative glomerulonephritis, sicca syndrome. Cryoglobulinaemia (CG) is a condition characterized by the presence of serum proteins that reversibly precipitate in the cold. The objective of the present work was to study the histopathological changes in neuromuscular biopsies in patients with HCV associated peripheral neuropathy, or myopathy; with and without cryoglobulinemia, and to assess the presence of HCV in nerve and muscle tissues of those patients which might clarify some pathogenetic mechanisms for neuropathy, and myopathy associated with HCV. Methods : The study was conducted on 17 cases of HCV infected patients with peripheral neuropathy and myositis. All patients were subjected to thorough laboratory investigations, neurological examination, electrophysiologic studies including nerve conduction, and needle EMG studies. Results : Histopathological examination of nerve biopsies showed features of vascultis in 2/10 cases, interstitial inflammatory infiltrates in 5/10. Muscle biopsies showed intense inflammatory reaction, degenerative changes in the muscles of 3/10 cases diagnosed as myositis. Immunohistochemical results, showed in nerve biopsies, 7/10 cases with positive reaction for HCV with nuclear and perinuclear staining.. Two patients showed positive reaction in the epineural, and endoneural blood vessels and a negative reaction in nerve bundles, while in five patients, reaction was only positive in the nerve bundles. In muscle biopsies, 7/10 cases showed positive reaction for HCV in the nuclei of the muscle fibers, including the cases presented with myositis. Conclusion : The presence of HCV particles in nerve and muscle biopsies of patients with peripheral neuropathy suggests a virus triggered immune mediated mechanism. PMID:21475428

  6. Therapeutic Benefit of Extended Thymosin β4 Treatment Is Independent of Blood Glucose Level in Mice with Diabetic Peripheral Neuropathy

    PubMed Central

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

    2015-01-01

    Peripheral neuropathy is a chronic complication of diabetes mellitus. To investigated the efficacy and safety of the extended treatment of diabetic peripheral neuropathy with thymosin β4 (Tβ4), male diabetic mice (db/db) at the age of 24 weeks were treated with Tβ4 or saline for 16 consecutive weeks. Treatment of diabetic mice with Tβ4 significantly improved motor (MCV) and sensory (SCV) conduction velocity in the sciatic nerve and the thermal and mechanical latency. However, Tβ4 treatment did not significantly alter blood glucose levels. Treatment with Tβ4 significantly increased intraepidermal nerve fiber density. Furthermore, Tβ4 counteracted the diabetes-induced axon diameter and myelin thickness reductions and the g-ratio increase in sciatic nerve. In vitro, compared with dorsal root ganglia (DRG) neurons derived from nondiabetic mice, DRG neurons derived from diabetic mice exhibited significantly decreased neurite outgrowth, whereas Tβ4 promoted neurite growth in these diabetic DRG neurons. Blockage of the Ang1/Tie2 signaling pathway with a neutralized antibody against Tie2 abolished Tβ4-increased neurite outgrowth. Our data demonstrate that extended Tβ4 treatment ameliorates diabetic-induced axonal degeneration and demyelination, which likely contribute to therapeutic effect of Tβ4 on diabetic neuropathy. The Ang1/Tie2 pathway may mediate Tβ4-induced axonal remodeling. PMID:25945352

  7. Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice

    PubMed Central

    Moon, Eunjung; Lee, Sung Ok; Kang, Tong Ho; Kim, Hye Ju; Choi, Sang Zin; Son, Mi-Won; Kim, Sun Yeou

    2014-01-01

    The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study. PMID:25414776

  8. Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats

    PubMed Central

    Lupachyk, Sergey; Watcho, Pierre; Shevalye, Hanna; Vareniuk, Igor; Obrosov, Alexander; Obrosova, Irina G.

    2013-01-01

    Evidence for an important role for Na+/H+ exchangers in diabetic complications is emerging. The aim of this study was to evaluate whether Na+/H+ exchanger 1 inhibition reverses experimental peripheral diabetic neuropathy. Control and streptozotocin-diabetic rats were treated with the specific Na+/H+ exchanger 1 inhibitor cariporide for 4 wk after 12 wk without treatment. Neuropathy end points included sciatic motor and sensory nerve conduction velocities, endoneurial nutritive blood flow, vascular reactivity of epineurial arterioles, thermal nociception, tactile allodynia, and intraepidermal nerve fiber density. Advanced glycation end product and markers of oxidative stress, including nitrated protein levels in sciatic nerve, were evaluated by Western blot. Rats with 12-wk duration of diabetes developed motor and sensory nerve conduction deficits, thermal hypoalgesia, tactile allodynia, and intraepidermal nerve fiber loss. All these changes, including impairment of nerve blood flow and vascular reactivity of epineurial arterioles, were partially reversed by 4 wk of cariporide treatment. Na+/H+ exchanger 1 inhibition was also associated with reduction of diabetes-induced accumulation of advanced glycation endproduct, oxidative stress, and nitrated proteins in sciatic nerve. In conclusion, these findings support an important role for Na+/H+ exchanger 1 in functional, structural, and biochemical manifestations of peripheral diabetic neuropathy and provide the rationale for development of Na+/H+ exchanger 1 inhibitors for treatment of diabetic vascular and neural complications. PMID:23736542

  9. Na+/H+ exchanger 1 inhibition reverses manifestation of peripheral diabetic neuropathy in type 1 diabetic rats.

    PubMed

    Lupachyk, Sergey; Watcho, Pierre; Shevalye, Hanna; Vareniuk, Igor; Obrosov, Alexander; Obrosova, Irina G; Yorek, Mark A

    2013-08-01

    Evidence for an important role for Na(+)/H(+) exchangers in diabetic complications is emerging. The aim of this study was to evaluate whether Na(+)/H(+) exchanger 1 inhibition reverses experimental peripheral diabetic neuropathy. Control and streptozotocin-diabetic rats were treated with the specific Na(+)/H(+) exchanger 1 inhibitor cariporide for 4 wk after 12 wk without treatment. Neuropathy end points included sciatic motor and sensory nerve conduction velocities, endoneurial nutritive blood flow, vascular reactivity of epineurial arterioles, thermal nociception, tactile allodynia, and intraepidermal nerve fiber density. Advanced glycation end product and markers of oxidative stress, including nitrated protein levels in sciatic nerve, were evaluated by Western blot. Rats with 12-wk duration of diabetes developed motor and sensory nerve conduction deficits, thermal hypoalgesia, tactile allodynia, and intraepidermal nerve fiber loss. All these changes, including impairment of nerve blood flow and vascular reactivity of epineurial arterioles, were partially reversed by 4 wk of cariporide treatment. Na(+)/H(+) exchanger 1 inhibition was also associated with reduction of diabetes-induced accumulation of advanced glycation endproduct, oxidative stress, and nitrated proteins in sciatic nerve. In conclusion, these findings support an important role for Na(+)/H(+) exchanger 1 in functional, structural, and biochemical manifestations of peripheral diabetic neuropathy and provide the rationale for development of Na(+)/H(+) exchanger 1 inhibitors for treatment of diabetic vascular and neural complications. PMID:23736542

  10. Pegylated Interferon Alpha–Associated Optic Neuropathy

    PubMed Central

    Berg, Kathleen T.; Nelson, Bruce; Harrison, Andrew R.; McLoon, Linda K.; Lee, Michael S.

    2013-01-01

    A 52-year-old man with chronic hepatitis C presented with painless, bilateral, simultaneous non-arteritic anterior ischemic optic neuropathy (NAION) and peripheral neuropathy. Symptoms began 19 weeks after starting peginterferon alpha-2a. The peripheral neuropathy and vision of the right eye improved, but the vision of the left eye worsened after stopping interferon. We identified 23 additional cases of NAION during interferon alpha therapy. At least 12 of these patients suffered bilateral NAION. Patients lost vision 1–40 weeks after initiating therapy. Of 21 eyes that had documented initial and follow-up acuities, 8 improved, 1 worsened, and the rest remained stable. One patient had a painful peripheral neuropathy. Treatment with interferon alpha may result in NAION. Discontinuation of therapy deserves consideration after weighing individual risks and benefits. PMID:20351572

  11. SUDOSCAN: A Simple, Rapid, and Objective Method with Potential for Screening for Diabetic Peripheral Neuropathy

    PubMed Central

    Selvarajah, Dinesh; Cash, Tom; Davies, Jennifer; Sankar, Adithya; Rao, Ganesh; Grieg, Marni; Pallai, Shillo; Gandhi, Rajiv; Wilkinson, Iain D.; Tesfaye, Solomon

    2015-01-01

    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

  12. Quantifying Dynamic Changes in Plantar Pressure Gradient in Diabetics with Peripheral Neuropathy

    PubMed Central

    Lung, Chi-Wen; Hsiao-Wecksler, Elizabeth T.; Burns, Stephanie; Lin, Fang; Jan, Yih-Kuen

    2016-01-01

    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 – first toe (T1), first metatarsal head (M1), second metatarsal head (M2), and heel (HL). Consistent with prior studies, PPP and PPG were significantly larger in the diabetic group compared with 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. PMID:27486576

  13. Identifying Predictors of Taxane-Induced Peripheral Neuropathy Using Mass Spectrometry-Based Proteomics Technology

    PubMed Central

    Chen, Emily I.; Crew, Katherine D.; Trivedi, Meghna; Awad, Danielle; Maurer, Mathew; Kalinsky, Kevin; Koller, Antonius; Patel, Purvi; Kim Kim, Jenny; Hershman, Dawn L.

    2015-01-01

    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

  14. Validity of the chemotherapy-induced peripheral neuropathy self-check sheet.

    PubMed

    Miyoshi, Yumiko; Onishi, Chie; Fujie, Mifumi; Senoo, Naomi; Wakatsuki, Ritsuko; Suzumiya, Junji

    2015-01-01

    Objective Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of some anti-cancer drugs. However, medical staff frequently encounter difficulties in ascertaining the severity of CIPN. We sought to develop a questionnaire in order to accurately assess CIPN. The validity of this questionnaire was compared with that of free-style interviews. Methods We developed the CIPN self-check sheet by analyzing existing self-assessment tools for CIPN and matching the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grades. From August to December 2011, 77 cancer patients participated in this study. In order to evaluate the validity of the CIPN self-check sheet compared with a free-style interview assessment, the cross-classification and κ coefficients between the CTCAE grades from each assessment and those from a comprehensive assessment were analyzed. The comprehensive assessment utilized information obtained from the medical examination, free-style interview and CIPN self-check sheet. Results Upon completion of the study, 248 CIPN self-check sheets were collected (median number of sheets per patient, 3; range, 1-14). The cross-classification analysis illustrated that the CIPN self-check sheet successfully identified all grade 3 cases. The coefficient of the CIPN self-check sheet was significantly higher than that of the free-style interviews [κ values: 0.988 (p<0.01) and 0.501 (p<0.01) for the self-check sheet and interviews, respectively]. Conclusion The CIPN self-check sheet can be used to assess the severity of CIPN based on the CTCAE grade more accurately than free-style interviews. PMID:25832934

  15. Identifying Predictors of Taxane-Induced Peripheral Neuropathy Using Mass Spectrometry-Based Proteomics Technology.

    PubMed

    Chen, Emily I; Crew, Katherine D; Trivedi, Meghna; Awad, Danielle; Maurer, Mathew; Kalinsky, Kevin; Koller, Antonius; Patel, Purvi; Kim Kim, Jenny; Hershman, Dawn L

    2015-01-01

    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

  16. The effects of goshajinkigan, a herbal medicine, on subjective symptoms and vibratory threshold in patients with diabetic neuropathy.

    PubMed

    Tawata, M; Kurihara, A; Nitta, K; Iwase, E; Gan, N; Onaya, T

    1994-12-16

    Goshajinkigan, a herbal medicine, has long been used in Japan to alleviate the subjective symptoms of diabetic neuropathy; however, its effects have not been confirmed objectively. We evaluated its effects on subjective symptoms and on vibration sensation in patients with diabetic neuropathy. The oral administration of 7.5 g/day of Goshajinkigan for 3 months (treatment period) relieved subjective symptoms of numbness in 9 of 13 patients. When the drug was discontinued for 2 months as a washout period, the subjective symptom worsened in 7 of 13 patients. Chi-square analysis revealed significant effects of Goshajiniagan on subjective symptoms (P < 0.001 for numbness and P < 0.05 for cold sensation). Vibration sensation was evaluated by measuring vibratory threshold using an SMV-5 vibrometer. There were significant changes in vibratory thresholds by paired t-test (P < 0.05) both in the upper and the lower extremities during the treatment and washout periods. Chi-square analysis also revealed a significant effect of Goshajinkigan on vibratory threshold (P < 0.01). There was no significant change in glycosylated hemoglobin as a whole during the study. These observations confirm that Goshajinkigan relieves subjective symptoms and demonstrate that it improves vibration sensation in patients with diabetic neuropathy. PMID:7705193

  17. Conditions Presenting with Symptoms of Peripheral Arterial Disease

    PubMed Central

    Sharma, Aditya M.; Norton, Patrick T.; Zhu, Daisy

    2014-01-01

    Peripheral artery disease (PAD) is estimated to affect more than 20% of people older than 65 years. The vast majority of patients with symptoms suggestive of PAD have atherosclerosis often associated with conventional vascular risk factors such as smoking, diabetes, dyslipidemia, and inflammation. A minority of people presenting with symptoms suggesting PAD have an alternative etiology. These groups of disorders are often underdiagnosed, and if diagnosed correctly the diagnosis may be delayed. Understanding these pathologies well is important, as they can be very debilitating and optimal treatment may vary significantly. Inappropriate treatment of these disorders can lead to worsening morbidity and mortality. This article discusses the underlying causes of nonatherosclerotic PAD, including the diagnosis and treatment of these disorders. PMID:25435652

  18. Effects of thai foot massage on balance performance in diabetic patients with peripheral neuropathy: a randomized parallel-controlled trial.

    PubMed

    Chatchawan, Uraiwan; Eungpinichpong, Wichai; Plandee, Piyawan; Yamauchi, Junichiro

    2015-01-01

    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 (P<0.05); however, when comparing between 2 groups, the Thai foot massage group showed better improvement in TUG than the control group (p<0.05). The Thai foot 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. PMID:25892354

  19. Effects of Thai Foot Massage on Balance Performance in Diabetic Patients with Peripheral Neuropathy: A Randomized Parallel-Controlled Trial

    PubMed Central

    Chatchawan, Uraiwan; Eungpinichpong, Wichai; Plandee, Piyawan; Yamauchi, Junichiro

    2015-01-01

    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 (P<0.05); however, when comparing between 2 groups, the Thai foot massage group showed better improvement in TUG than the control group (p<0.05). The Thai foot 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. PMID:25892354

  20. A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA

    PubMed Central

    Wos, Edward J.; Qin, Rui; Mattar, Bassam I.; Green, Nathan Benjamin; Lanier, Keith S.; Bearden, James Dewitt; Kugler, John W.; Hoff, Kay L.; Reddy, Pavan S.; Rowland, Kendrith M.; Riepl, Mike; Christensen, Bradley; Loprinzi, Charles L.

    2012-01-01

    Background Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome chronic symptom that has no proven pharmacologic treatment. The purpose of this double-blind randomized placebo-controlled trial was to evaluate a novel compounded topical gel for this problem. Methods Patients with CIPN were randomized to baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) versus placebo (PLO) to determine its effect on numbness, tingling, pain, and function. The primary endpoint was the baseline-adjusted sensory subscale of the EORTC QLQ-CIPN20, at 4 weeks. Results Data in 208 patients reveal a trend for improvement that is greater in the BAK-PLO arm over placebo in both the sensory (p=0.053) and motor subscales (p=0.021). The greatest improvements were related to the symptoms of tingling, cramping, and shooting/burning pain in the hands as well as difficulty in holding a pen. There were no undesirable toxicities associated with the BAK-PLO and no evidence of systemic toxicity. Conclusion Topical treatment with BAK-PLO appears to somewhat improve symptoms of CIPN. This topical gel was well tolerated, without evident systemic toxicity. Further research is needed with increased doses to better clarify the clinical role of this treatment in CIPN. PMID:20496177

  1. The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings

    PubMed Central

    Cavaletti, G.; Cornblath, D. R.; Merkies, I. S. J.; Postma, T. J.; Rossi, E.; Frigeni, B.; Alberti, P.; Bruna, J.; Velasco, R.; Argyriou, A. A.; Kalofonos, H. P.; Psimaras, D.; Ricard, D.; Pace, A.; Galiè, E.; Briani, C.; Dalla Torre, C.; Faber, C. G.; Lalisang, R. I.; Boogerd, W.; Brandsma, D.; Koeppen, S.; Hense, J.; Storey, D.; Kerrigan, S.; Schenone, A.; Fabbri, S.; Valsecchi, M. G.; Mazzeo, A.; Pace, A.; Pessino, A.; Schenone, A.; Toscano, A.; Argyriou, A.A.; Brouwer, B.; Frigeni, B.; Piras, B.; Briani, C.; Dalla Torre, C.; Dominguez Gonzalez, C.; Faber, C. G.; Tomasello, C.; Binda, D.; Brandsma, D.; Cortinovis, D.; Psimaras, D.; Ricard, D.; Storey, D.; Cornblath, D.R.; Galiè, E.; Lindeck Pozza, E.; Rossi, E.; Vanhoutte, E.K.; Lanzani, F.; Pastorelli, F.; Altavilla, G.; Cavaletti, G.; Granata, G.; Kalofonos, H.P.; Ghignotti, I.; Merkies, I.S.J.; Bruna, J.; Hense, J.; Heimans, J.J.; Mattavelli, L.; Padua, L.; Reni, L.; Bakkers, M.; Boogerd, M.; Campagnolo, M.; Cazzaniga, M.; Eurelings, M.; Leandri, M.; Lucchetta, M.; Penas Prado, M.; Russo, M.; Valsecchi, M.G.; Piatti, M.L.; Alberti, P.; Bidoli, P.; Grant, R.; Plasmati, R.; Velasco, R.; Lalisang, R.I.; Meijer, R.J.; Fabbri, S.; Dorsey, S. G.; Galimberti, S.; Kerrigan, S.; Koeppen, S.; Postma, T.J.; Boogerd, W.; Grisold, W.

    2013-01-01

    Background Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. Patients and methods After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. Results Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test–retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. Conclusion Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures. PMID:22910842

  2. Clinical experience with desvenlafaxine in treatment of pain associated with diabetic peripheral neuropathy

    PubMed Central

    Allen, Rob; Sharma, Uma; Barlas, Suna

    2014-01-01

    Purpose To assess the safety and efficacy of the serotonin–norepinephrine reuptake inhibitor desvenlafaxine in adults with painful diabetic peripheral neuropathy (DPN). ClinicalTrials.gov identifiers NCT00283842, NCT01050218. Patients and methods This was a 13-week, randomized, double-blind, placebo-controlled, fixed-dose study of desvenlafaxine in adults with painful DPN. The primary efficacy endpoint was change from baseline in numeric rating scale (NRS) score. Patients who completed the 13-week trial could continue in a 9-month open-label, flexible-dose extension study. Results A total of 412 patients were randomized to treatment with placebo or desvenlafaxine 50, 100, 200, or 400 mg/day. Of those, 240 patients continued in the extension study. After a planned interim analysis, conducted when the first 225 patients had completed 6 weeks of treatment in the short-term study, randomization to the 50 mg or 400 mg doses was stopped. At week 13, the mean change from baseline in NRS score was significantly greater compared with placebo in the desvenlafaxine 200 mg (difference [95% confidence interval {CI}]: 1.10 [0.50 to 1.70]; P<0.001) and 400 mg groups (0.91 [95% CI: 0.23 to 1.59]; P=0.027); differences from placebo were not statistically significant for the 50 mg (0.58 [95% CI: −0.08 to 1.25]) and 100 mg (0.59 [95% CI: –0.03 to 1.21]) groups. Nausea and dizziness were the most common treatment-emergent adverse events reported in the short-term study, and the most common adverse events leading to discontinuation in the short-term study and the extension. Adverse events rates were dose-dependent in the short-term studies. Conclusion Desvenlafaxine was effective in relieving pain associated with DPN at doses of 200 and 400 mg/day, and improved activity impairment at all doses assessed. Desvenlafaxine was generally well-tolerated in the short-term and long-term studies. PMID:25018648

  3. Sonographic evaluation of the peripheral nerves in hereditary neuropathy with liability to pressure palsies: a case report.

    PubMed

    Kim, Se Hwa; Yang, Seung Nam; Yoon, Joon Shik; Park, Bum Jun

    2014-02-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominantly inherited disorder that affects peripheral nerves by repeated focal pressure. HNPP can be diagnosed by clinical findings, electrodiagnostic studies, histopathological features, and genetic analysis. Ultrasonography is increasingly used for the diagnosis of neuromuscular diseases; however, sonographic features of HNPP have not been clearly defined. We report the sonographic findings and comparative electrodiagnostic data in a 73-year-old woman with HNPP, confirmed by genetic analysis. The cross-sectional areas of peripheral nerves were enlarged at typical nerve entrapment sites, but enlargement at non-entrapment sites was uncommon. These sonographic features may be helpful for diagnosis of HNPP when electrodiagnostic studies are suspicious of HNPP and/or gene study is not compatible. PMID:24639934

  4. Sonographic Evaluation of the Peripheral Nerves in Hereditary Neuropathy With Liability to Pressure Palsies: A Case Report

    PubMed Central

    Kim, Se Hwa; Yoon, Joon Shik; Park, Bum Jun

    2014-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominantly inherited disorder that affects peripheral nerves by repeated focal pressure. HNPP can be diagnosed by clinical findings, electrodiagnostic studies, histopathological features, and genetic analysis. Ultrasonography is increasingly used for the diagnosis of neuromuscular diseases; however, sonographic features of HNPP have not been clearly defined. We report the sonographic findings and comparative electrodiagnostic data in a 73-year-old woman with HNPP, confirmed by genetic analysis. The cross-sectional areas of peripheral nerves were enlarged at typical nerve entrapment sites, but enlargement at non-entrapment sites was uncommon. These sonographic features may be helpful for diagnosis of HNPP when electrodiagnostic studies are suspicious of HNPP and/or gene study is not compatible. PMID:24639934

  5. Seizure, spinal schwannoma, peripheral neuropathy and pulmonary stenosis - A rare combination in a patient of Neurofibromatosis 1.

    PubMed

    Ray, Avas Chandra; Karjyi, Nabendu; Roy, Achintya Narayan; Dutta, Arup Kumar; Biswas, Atanu

    2012-01-01

    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. PMID:22412275

  6. Peripheral neuropathy associated with monoclonal IgG of undetermined significance: clinical, electrophysiologic, pathologic and therapeutic study of 14 cases.

    PubMed

    Hermosilla, E; Lagueny, A; Vital, C; Vital, A; Ferrer, X; Steck, A; Julien, J

    1996-01-01

    Fourteen patients with peripheral neuropathy and monoclonal IgG of undetermined significance are reported with a retrospective study of the clinical features, electrophysiologic and sural nerve biopsy findings. There were two groups. Five patients had a relapsing chronic sensorimotor polyneuropathy with clinical (5/5), electrophysiologic (4/5) and pathologic (5/5) features compatible with chronic inflammatory demyelinating polyneuropathies (CIDP). The nine others had a slowly progressive sensory (5/9) (SPNP) or sensorimotor (4/9) (SMPNP) axonal polyneuropathy. Four patients of the first group were treated with intravenous human immunoglobulin (400 mg/kg/day for five days) with significant clinical improvement. The motor conduction velocities and distal latencies of two of these patients improved following treatment, thus matching the clinical improvement. Our results on peripheral nerve biopsies confirm the differentiation of patients with CIDP from those with SMPNP and SPNP. There was no specific immunologic serologic reactivity in any of the cases. PMID:10975722

  7. SCN9A Variants May be Implicated in Neuropathic Pain Associated With Diabetic Peripheral Neuropathy and Pain Severity

    PubMed Central

    Cheng, Peter; Favis, Reyna; Wickenden, Alan; Romano, Gary; Wang, Hao

    2015-01-01

    Objectives: Previous studies have established the role of SCN9A in various pain conditions, including idiopathic small fiber neuropathy. In the present study, we interrogate the relationship between common and rare variants in SCN9A gene and chronic neuropathic pain associated with diabetic peripheral neuropathy. Design: Using a cohort of 938 patients of European ancestry with chronic neuropathic pain associated with diabetic peripheral neuropathy enrolled in 6 clinical studies and 2 controls (POPRES, n=2624 and Coriell, n=1029), we examined the relationship between SCN9A variants and neuropathic pain in a case-control study using a 2-stage design. The exonic regions of SCN9A were sequenced in a subset of 244 patients with neuropathic pain, and the variants discovered were compared with POPRES control (stage 1). The top associated variants were followed up by genotyping in the entire case collection and Coriell controls restricting the analysis to the matching patients from the United States and Canada only (stage 2). Results: Seven variants were found to be associated with neuropathic pain at the sequencing stage. Four variants (Asp1908Gly, Val991Leu/Met932Leu, and an intronic variant rs74449889) were confirmed by genotyping to occur at a higher frequency in cases than controls (odds ratios ∼2.1 to 2.6, P=0.05 to 0.009). Val991Leu/Met932Leu was also associated with the severity of pain as measured by pain score Numeric Rating Scale (NRS-11, P=0.047). Val991Leu/Met932Leu variants were in complete linkage disequilibrium and previously shown to cause hyperexcitability in dorsal root ganglia neurons. Conclusions: The association of SCN9A variants with neuropathic pain and pain severity suggests a role of SCN9A in the disease etiology of neuropathic pain. PMID:25585270

  8. Altered discharges of spinal neurons parallel the behavioral phenotype shown by rats with bortezomib related chemotherapy induced peripheral neuropathy

    PubMed Central

    Robinson, Caleb R.; Zhang, Hongmei; Dougherty, Patrick M.

    2014-01-01

    Bortezomib is a first generation proteasome inhibitor that is the frontline chemotherapy for multiple myeloma with the chief dose-limiting side effect of painful peripheral neuropathy. The goal of this study was to define the behavioral phenotype in a preclinical model of bortezomib chemotherapy-induced peripheral neuropathy (CIPN) and to test whether this is matched by changes in the physiological responses of spinal wide dynamic range neurons. Sprague-Dawley rats were treated with four injections of bortezomib at four doses, 0.05mg/kg, 0.10 mg/kg, 0.15 mg/kg, 0.20 mg/kg, or equal volume of saline. All doses of bortezomib above 0.05mg/kg produced showed significant dose-dependent mechanical hyperalgesia that was fully established at 30 days after treatment and that recovered to baseline levels by day 69 after treatment. Thermal, cold, and motor testing were all unaffected by treatment with bortezomib. Spinal wide dynamic range (WDR) neurons in rats with confirmed bortzomib-related CIPN showed an increase in number of evoked discharges to mechanical stimuli and exaggerated after-discharges in rats with bortezomib CIPN. PMID:24949562

  9. The role of sulfoglucuronosyl glycosphingolipids in the pathogenesis of monoclonal IgM paraproteinemia and peripheral neuropathy

    PubMed Central

    ARIGA, Toshio

    2011-01-01

    In IgM paraproteinemia and peripheral neuropathy, IgM M-protein secretion by B cells leads to a T helper cell response, suggesting that it is antibody-mediated autoimmune disease involving carbohydrate epitopes in myelin sheaths. An immune response against sulfoglucuronosyl glycosphingolipids (SGGLs) is presumed to participate in demyelination or axonal degeneration in the peripheral nervous system (PNS). SGGLs contain a 3-sulfoglucuronic acid residue that interacts with anti-myelin-associated glycoprotein (MAG) and the monoclonal antibody anti-HNK-1. Immunization of animals with sulfoglucuronosyl paragloboside (SGPG) induced anti-SGPG antibodies and sensory neuropathy, which closely resembles the human disease. These animal models might help to understand the disease mechanism and lead to more specific therapeutic strategies. In an in vitro study, destruction or malfunction of the blood-nerve barrier (BNB) was found, resulting in the leakage of circulating antibodies into the PNS parenchyma, which may be considered as the initial key step for development of disease. PMID:21785257

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

    PubMed

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

    2014-08-01

    Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased cleaved caspase-3 expression, induced the loss of primary afferent terminal fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn, indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of macrophage in vitro study. Intrathecal or systemic injection of CX3CL1 neutralizing antibody blocked paclitaxel-induced macrophage recruitment and neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia. Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy. PMID:24681252

  11. Recurrent Episodes of Stroke-Like Symptoms in a Patient with Charcot-Marie-Tooth Neuropathy X Type 1

    PubMed Central

    Wu, Ning; Said, Sarita; Sabat, Shyamsunder; Wicklund, Matthew; Stahl, Mark C.

    2015-01-01

    Charcot-Marie-Tooth disease (CMT), also known as hereditary motor sensory neuropathy, is a heterogeneous group of disorders best known for causing inherited forms of peripheral neuropathy. The X-linked form, CMTX1, is caused by mutations in the gap junction protein beta 1 (GJB1) gene, expressed both by peripheral Schwann cells and central oligodendrocytes. Central manifestations are known but are rare, and there are few case reports of leukoencephalopathy with transient or persistent neurological deficits in patients with this CMT subtype. Here, we report the case of a man with multiple male and female family members affected by neuropathy who carries a pathologic mutation in GJB1. He has experienced three transient episodes with variable neurological deficits over the course of 7 years with corresponding changes on magnetic resonance imaging (MRI). This case illustrates CMT1X as a rare cause of transient neurological deficit and demonstrates the evolution of associated reversible abnormalities on MRI over time. To the best of our knowledge, this report provides the longest period of serial imaging in a single patient with this condition in the English language literature. PMID:26955336

  12. Plantar Pressure in Diabetic Peripheral Neuropathy Patients with Active Foot Ulceration, Previous Ulceration and No History of Ulceration: A Meta-Analysis of Observational Studies

    PubMed Central

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

    2014-01-01

    Aims 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. Methods 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). Results Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290–0.811, p<0.001; and 0.762, 95% CI 0.303–1.221, p = 0.001, respectively). Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181– 0.753, p = 0.001). Statistical heterogeneity between studies was moderate. Conclusions Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy

  13. Prospective induction of peripheral neuropathy by the use of Tartarian Buckwheat.

    PubMed

    Yang, Fei; Yu, Sheng-Yuan; Wang, Yan; Wang, Rong-Fei; Jing, Feng

    2014-12-15

    Tartarian Buckwheat is an effective hypoglycemic medicinal herb. Its main active ingredients are flavonoids. We report here 5 cases of new onset polyneuropathy with dyskinesia prospectively induced by tartarian buckwheat products. Clinical and electrophysiological evidence along with laboratory tests were reviewed and analyzed. All patients were male, with an average age of 52.2 ± 10.9 years old (range: 40-66 years) and had a recent history of using tartarian buckwheat for diabetes therapy. The average time of use was 2.5 ± 1.0 months (range: 1.5-4 months). The average duration of the clinical course was 0.9 ± 0.2 months (range: 0.5-1 months). Symptoms included numbness and weakness of the limbs (5/5, 100%), hoarseness (4/5, 80%), dysphagia (1/5, 20%), bilateral facial paralysis (1/5, 20%), urinary disorders (3/5, 60%) and gonadal abnormality (4/4, 100%). Nerve conduction studies suggested more severe damages in motor nerves than sensory nerves. All the patients showed abnormality on Von Frey filaments determination. Hence, tartarian buckwheat products may cause toxic peripheral nerve lesion and the use of herbal medication needs to be better regulated and closely monitored. PMID:25300770

  14. A Case of Peripheral Neuropathy From Contact With Military Radar Equipment

    PubMed Central

    Tenenhaus, Mayer; Potenza, Bruce; Li, Andrew

    2010-01-01

    Complex early and late neuropathies resulting from direct and conductive electrical patterns of injury are disabling and extremely challenging to manage. We report a patient who suffered acute onset of right-hand weakness and decreased sensation following a radar equipment–related electrical injury. He received a carpal and Guyon tunnel release, regaining sensation and strength to his right hand by the first postoperative day. PMID:20076783

  15. Association of Thymidylate Synthase Polymorphisms with Acute Pancreatitis and/or Peripheral Neuropathy in HIV-Infected Patients on Stavudine-Based Therapy

    PubMed Central

    Torres, Ferran; Salazar, Juliana; Gutierrez, Maria del Mar; Mateo, Maria Gracia; Martínez, Esteban; Domingo, Joan Carles; Fernandez, Irene; Villarroya, Francesc; Ribera, Esteban; Vidal, Francesc; Baiget, Montserrat

    2013-01-01

    Background Low expression thymidylate synthase (TS) polymorphism has been associated with increased stavudine triphosphate intracellular (d4T-TP) levels and the lipodystrophy syndrome. The use of d4T has been associated with acute pancreatitis and peripheral neuropathy. However, no relationship has ever been proved between TS polymorphisms and pancreatitis and/or peripheral neuropathy. Methods We performed a case-control study to assess the relationship of TS and methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms with acute pancreatitis and/or peripheral neuropathy in patients exposed to d4T. Student’s t test, Pearson’s correlations, one-way ANOVA with Bonferroni correction and stepwise logistic regression analyses were done. Results Forty-three cases and 129 controls were studied. Eight patients (18.6%) had acute pancreatitis, and 35 (81.4%) had peripheral neuropathy. Prior AIDS was more frequent in cases than in controls (OR = 2.36; 95%CI 1.10–5.07, P = 0.0247). L7ow expression TS and MTHFR genotype associated with increased activity were more frequent in patients with acute pancreatitis and/or peripheral neuropathy than in controls (72.1% vs. 46.5%, OR = 2.97; 95%CI: 1.33–6.90, P = 0.0062, and 79.1% vs. 56.6%, OR = 2.90, 95%CI: 1.23–7.41, P = 0.0142, respectively). Independent positive or negative predictors for the development of d4T-associated pancreatitis and/or peripheral neuropathy were: combined TS and MTHFR genotypes (reference: A+A; P = 0.002; ORA+B = 0.34 [95%CI: 0.08 to 1.44], ORB+A = 3.38 [95%CI: 1.33 to 8.57], ORB+B = 1.13 [95%CI: 0.34 to 3.71]), nadir CD4 cell count >200 cells/mm3 (OR = 0.38; 95%CI: 0.17–0.86, P = 0.021), and HALS (OR = 0.39 95%CI: 0.18–0.85, P = 0.018). Conclusions Low expression TS plus a MTHFR genotype associated with increased activity is associated with the development of peripheral neuropathy in d4T-exposed patients. PMID:23468971

  16. Neuromyotonia in hereditary motor neuropathy.

    PubMed Central

    Hahn, A F; Parkes, A W; Bolton, C F; Stewart, S A

    1991-01-01

    Two siblings with a distal motor neuropathy experienced cramping and difficulty in relaxing their muscles after voluntary contraction. Electromyographic recordings at rest revealed repetitive high voltage spontaneous electrical discharges that were accentuated after voluntary contraction and during ischaemia. Regional neuromuscular blockage with curare indicated hyperexcitability of peripheral nerve fibres and nerve block suggested that the ectopic activity originated in proximal segments of the nerve. Symptoms were improved with diphenylhydantoin, carbamazepine and tocainide. Images PMID:1851512

  17. Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia

    PubMed Central

    Schmidt, Wolfgang M.; Rutledge, S. Lane; Schüle, Rebecca; Mayerhofer, Benjamin; Züchner, Stephan; Boltshauser, Eugen; Bittner, Reginald E.

    2015-01-01

    Hereditary ataxias comprise a group of genetically heterogeneous disorders characterized by clinically variable cerebellar dysfunction and accompanied by involvement of other organ systems. The molecular underpinnings for many of these diseases are widely unknown. Previously, we discovered the disruption of Scyl1 as the molecular basis of the mouse mutant mdf, which is affected by neurogenic muscular atrophy, progressive gait ataxia with tremor, cerebellar vermis atrophy, and optic-nerve thinning. Here, we report on three human individuals, from two unrelated families, who presented with recurrent episodes of acute liver failure in early infancy and are affected by cerebellar vermis atrophy, ataxia, and peripheral neuropathy. By whole-exome sequencing, compound-heterozygous mutations within SCYL1 were identified in all affected individuals. We further show that in SCYL1-deficient human fibroblasts, the Golgi apparatus is massively enlarged, which is in line with the concept that SCYL1 regulates Golgi integrity. Thus, our findings define SCYL1 mutations as the genetic cause of a human hepatocerebellar neuropathy syndrome. PMID:26581903

  18. Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia.

    PubMed

    Schmidt, Wolfgang M; Rutledge, S Lane; Schüle, Rebecca; Mayerhofer, Benjamin; Züchner, Stephan; Boltshauser, Eugen; Bittner, Reginald E

    2015-12-01

    Hereditary ataxias comprise a group of genetically heterogeneous disorders characterized by clinically variable cerebellar dysfunction and accompanied by involvement of other organ systems. The molecular underpinnings for many of these diseases are widely unknown. Previously, we discovered the disruption of Scyl1 as the molecular basis of the mouse mutant mdf, which is affected by neurogenic muscular atrophy, progressive gait ataxia with tremor, cerebellar vermis atrophy, and optic-nerve thinning. Here, we report on three human individuals, from two unrelated families, who presented with recurrent episodes of acute liver failure in early infancy and are affected by cerebellar vermis atrophy, ataxia, and peripheral neuropathy. By whole-exome sequencing, compound-heterozygous mutations within SCYL1 were identified in all affected individuals. We further show that in SCYL1-deficient human fibroblasts, the Golgi apparatus is massively enlarged, which is in line with the concept that SCYL1 regulates Golgi integrity. Thus, our findings define SCYL1 mutations as the genetic cause of a human hepatocerebellar neuropathy syndrome. PMID:26581903

  19. Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain

    PubMed Central

    Labuz, Dominika; Celik, Melih Ö.; Zimmer, Andreas; Machelska, Halina

    2016-01-01

    Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment. PMID:27605249

  20. Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain.

    PubMed

    Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina

    2016-01-01

    Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment. PMID:27605249

  1. Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

    PubMed Central

    Pop-Busui, Rodica; Lu, Jiang; Lopes, Neuza; Jones, Teresa L. Z.

    2009-01-01

    We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass-Angioplasty-Revascularization-Investigation-2-Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing versus insulin-providing treatments for diabetes. 2368 patients with type 2 diabetes and CAD were evaluated. DPN was defined as clinical examination score >2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression, adjusted for multiple covariates including age, sex, HbA1c, diabetes duration. 51% BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR1.57, 1.15, 2.13). Patients on sulfonylurea or combination of sulfonylurea/metformin/TZD had marginally higher rates of DPN than the metformin/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN. PMID:19335534

  2. The Rehabilitation of Oncological Patients Presenting Neuropathies

    PubMed Central

    MICU, ELENA CLAUDIA; IRSAY, LASZLO

    2014-01-01

    The International Association for the Study of Pain (IASP 2011) defines neuropathic pain as “the pain caused by an injury or disease of the somatosensory portion of the nervous system”. The central neuropathic pain is defined as “the pain caused by an injury or disease of the central somatosensory central nervous system”, whereas the peripheral neuropathic pain is defined as “the pain caused by an injury or disease of the peripheral somatosensory nervous system” [1]. The peripheral neuropathy describes any affection of the peripheral nervous system. The etiology is vast, there being a number of over 100 possible causes, which causes the global morbidity rate to reach approximately 2.4%. The chronic nature of the pain superposes the everyday routine and leads to the high intake of medication for pain alleviation. The number of cases of neuroplasia has always increased today. This disturbing diagnosis which can potentiate the signs and symptoms of peripheral neuropathy as well as reduce and limit the treatment options associated with neuropathies. The treatment presupposes a multidisciplinary approach, while the solution to prevent complications involves the control of risk factors and pathophysiological treatment. Chemotherapy-induced peripheral neuropathy (CPIN) is a significant disabling symptom that is tightly connected to the administration of neurotoxic cytostatic agents used for the treatment of neoplasia. CPIN compromises the quality of life and produces pain or discomfort [2]. I have sought to produce a presentation of the medicated and physical-kinetic treatment options that have proved their effectiveness during clinical studies or random trials and can be applied to cancer patients presenting with symptoms associated with peripheral neuropathy, namely with neuropathic pain, and support it with arguments. PMID:26528000

  3. Waldenstrom's Macroglobulinemia and Peripheral Neuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes with a Bleeding Diathesis and Rash.

    PubMed

    Haider, S; Latif, T; Hochhausler, A; Lucas, F; Abdel Karim, N

    2013-01-01

    We report a case of a 29-year-old male who presented with paraesthesia and skin lesions with excessive bleeding after skin biopsy leading to hematology consultation. He was found to have prolonged partial thromboplastin time (PTT) and monoclonal gammopathy on serum protein electrophoresis (SPEP). He experienced excessive bleeding leading to hospitalization after bone marrow biopsy and required blood transfusion. He was diagnosed with Waldenstrom's Macroglobulinemia (WM), based on the presence of IgM- κ type monoclonal (M) protein and infiltration of lymphoplasmacytic cells identified in bone marrow aspirates. He was noticed to have features of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome). This is a very rare case of WM with POEMS syndrome which responded to chemotherapy using bortezomib, steroids, and rituximab. PMID:24455363

  4. Late onset brachial artery thrombosis and total temporary peripheral neuropathy in a child with humerus supracondylar fracture: a case report.

    PubMed

    Ege, Tolga; Türkkan, Selim; Günay, Celalettin; Külahçı, Yalçın; Kürklü, Mustafa

    2015-01-01

    Pediatric supracondylar fractures of the humerus are generally associated with neurovascular complications due to the deformity and sharp nature of bone fragments. When treated inadequately, these injuries may result in catastrophic complications, such as Volkmann's contracture and amputation. To our knowledge, late onset brachial arterial thrombosis and total temporary peripheral neuropathy after surgery of pediatric supracondylar fracture in the setting of normal preoperative vascular examination has not been reported yet. In this study, a 2-year and 6- month-old girl, who had delayed brachial arterial thrombosis after a displaced humerus supracondylar fracture surgery treated with embolectomy, was reported. Total lesion of median, ulnar and radial nerves completely resolved four months after surgery. Close neurovascular monitoring on the postoperative phase especially in severely displaced supracondylar fractures is strongly emphasized even in the setting of well-perfused hand. PMID:25779718

  5. Central or peripheral delivery of an adenosine A1 receptor agonist improves mechanical allodynia in a mouse model of painful diabetic neuropathy.

    PubMed

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

    2015-01-29

    Diabetic peripheral neuropathy is a common complication of diabetes mellitus, and a significant proportion of individuals suffer debilitating pain that significantly affects their quality of life. Unfortunately, symptomatic treatment options have limited efficacy, and often carry significant risk of systemic adverse effects. Activation of the adenosine A1 receptor (A1R) by the analgesic small molecule adenosine has been shown to have antinociceptive benefits in models of inflammatory and neuropathic pain. The current study used a mouse model of painful diabetic neuropathy to determine the effect of diabetes on endogenous adenosine production, and if central or peripheral delivery of adenosine receptor agonists could alleviate signs of mechanical allodynia in diabetic mice. Diabetes was induced using streptozocin in male A/J mice. Mechanical withdrawal thresholds were measured weekly to characterize neuropathy phenotype. Hydrolysis of AMP into adenosine by ectonucleotidases was determined in the dorsal root ganglia (DRG) and spinal cord at 8 weeks post-induction of diabetes. AMP, adenosine and the specific A1R agonist, N(6)-cyclopentyladenosine (CPA), were administered both centrally (intrathecal) and peripherally (intraplantar) to determine the effect of activation of adenosine receptors on mechanical allodynia in diabetic mice. Eight weeks post-induction, diabetic mice displayed significantly decreased hydrolysis of extracellular AMP in the DRG; at this same time, diabetic mice displayed significantly decreased mechanical withdrawal thresholds compared to nondiabetic controls. Central delivery AMP, adenosine and CPA significantly improved mechanical withdrawal thresholds in diabetic mice. Surprisingly, peripheral delivery of CPA also improved mechanical allodynia in diabetic mice. This study provides new evidence that diabetes significantly affects endogenous AMP hydrolysis, suggesting that altered adenosine production could contribute to the development of

  6. Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial.

    PubMed

    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

    2016-02-01

    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 < 0.05) with older age (OR = 1.04 per year), female gender (OR = 1.64), Tuberculosis (TB; OR = 1.86), smoking (OR = 1.60), higher plasma creatinine (OR = 1.09 per 0.1 mg/dl increase), CD4 count (OR = 0.83 per doubling) and not consuming alcohol (OR = 0.55). SPN prevalence decreased to 17% by week 96 (p = 0.0002) following similar trends in all study groups (p = 0.30). Asymptomatic PN (APN) increased over the same period from 21 to 29% (p = 0.0002). Signs suggestive of PN (regardless of symptoms) returned to baseline levels by week 96. At weeks 48 and 96, after adjusting for time-updated associations above and baseline CD4 count and viral load, SPN was strongly associated with TB (p < 0.0001). In summary, SPN prevalence was significantly reduced with PI-based second-line 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. PMID:26323809

  7. Primary afferent input critical for maintaining spontaneous pain in peripheral neuropathy.

    PubMed

    Haroutounian, Simon; Nikolajsen, Lone; Bendtsen, Thomas F; Finnerup, Nanna B; Kristensen, Anders D; Hasselstrøm, Jørgen B; Jensen, Troels S

    2014-07-01

    Central sensitization after peripheral nerve injury may result in ectopic neuronal activity in the spinal cord dorsal horn, implying a potential autonomous pain-generating mechanism. This study used peripheral nerve blockade and systemic lidocaine administration, with detailed somatosensory assessment, to determine the contribution of primary afferent input in maintaining peripheral neuropathic pain. Fourteen patients with neuropathic pain (7 with unilateral foot pain due to peripheral nerve injury and 7 with bilateral pain in the feet due to distal polyneuropathy) underwent comprehensive characterization of somatosensory function by quantitative sensory testing. Patients were then administered an ultrasound-guided peripheral nerve block with lidocaine and intravenous lidocaine infusion in randomized order. The effect of these interventions on spontaneous pain intensity and on evoked cold, warm, pinprick, and brush responses was assessed at each session. All patients had sensory disturbances at baseline. The peripheral nerve block resulted in a complete abolition of ipsilateral pain within 10 min (median) in all patients, with lidocaine plasma concentrations being too low to account for a systemic effect of the drug. Intravenous lidocaine infusion reduced the spontaneous pain by 45.5% (±31.7%), and it reduced mechanical and thermal hypersensitivity in most patients who displayed such signs. However, the improvement in evoked hypersensitivity was not related to the effect of the drug on spontaneous pain intensity. This study demonstrated that regardless of the individual somatosensory phenotype and signs of central sensitization, primary afferent input is critical for maintaining neuropathic pain in peripheral nerve injury and distal polyneuropathy. PMID:24704366

  8. Leprosy: a 'common' and curable cause of peripheral neuropathy with skin lesions.

    PubMed

    Breen, D P; Deeb, J; Vaidya, S; Lockwood, D N; Radunovic, A

    2015-03-01

    Leprosy (or Hansen's disease) is a curable chronic infectious disease caused by the acid-fast bacillus Mycobacterium leprae. While leprosy remains one of the most common causes of neuropathy worldwide, its rarity in the UK means that many doctors are unfamiliar with the typical clinical features. This is problematic because early recognition and treatment is vital in order to minimise disease-related complications such as nerve injury. We describe a 75-year-old man who presented with multiple mononeuropathy (mononeuritis multiplex, particularly affecting the ulnar nerves) and typical granulomatous skin lesions, in whom the diagnosis was made on the basis of skin biopsy. We highlight the clinical features, investigations and treatment of the patient, and provide information about the epidemiology and pathogenesis of leprosy. PMID:25874829

  9. Surgical treatment of a tomaculous neuropathy.

    PubMed

    Taggart, T F; Allen, T R

    2001-08-01

    Compressive neuropathy of the ulnar nerve at the elbow is the second most common nerve entrapment in the upper limb. Eight possible anatomical points of constriction have been identified. The most common constriction being the intermuscular septum proximally or between the two heads of the flexor carpi ulnaris in the cubital canal distally. Surgical release is successful in 80-90% of cases. Certain rare genetic conditions can predispose susceptible peripheral nerves to similar compressive neuropathies but there is no literature on surgical treatment of such patients. We present a case of hereditary neuropathy with liability to pressure palsy (HNPP) often known as 'tomaculous' neuropathy, in a patient with ulnar nerve symptoms who underwent a surgical release. PMID:11523718

  10. Disrupted Sleep and Delayed Recovery from Chronic Peripheral Neuropathy are Distinct Phenotypes in a Rat Model of Metabolic Syndrome

    PubMed Central

    Muncey, Aaron R.; Saulles, Adam R.; Koch, Lauren G.; Britton, Steven L.; Baghdoyan, Helen A.; Lydic, Ralph

    2010-01-01

    Background 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. Methods Rats were from a breeding strategy that selected for low aerobic capacity runners (LCR) and high aerobic capacity runners (HCR). Four different phenotypes were quantified. Rats (n=12) underwent von Frey sensory testing, thermal nociceptive testing (n=12), electrographic recordings of sleep and wakefulness (n=16), and thermal nociceptive testing before and for six weeks after a unilateral chronic neuropathy of the sciatic nerve (n=14). Results Paw withdrawal latency to a thermal nociceptive stimulus was significantly (P<0.01) less in LCR than HCR rats. There were significant differences in sleep. LCR rats spent significantly (P<0.01) more time awake (18%) and less time in non-rapid eye movement sleep (−19%) than HCR rats. Non-rapid eye movement sleep episodes were of shorter duration (−34%) in LCR than HCR rats. Rapid eye movement sleep of LCR rats was significantly more fragmented than Rapid eye movement sleep of HCR rats. LCR rats required two weeks longer than HCR rats to recover from peripheral neuropathy. Conclusions Rodents with low aerobic capacity exhibit features homologous to human metabolic syndrome. This rodent model offers a novel tool for characterizing the mechanisms through which low aerobic function and obesity might confer increased risks for anesthesia. PMID:20938334

  11. Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort.

    PubMed

    Pop-Busui, Rodica; Lu, Jiang; Lopes, Neuza; Jones, Teresa L Z

    2009-03-01

    We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score >2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15-2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN. PMID:19335534

  12. Use of engineered Schwann cells in peripheral neuropathy: Hopes and hazards.

    PubMed

    Lehmann, Helmar C; Höke, Ahmet

    2016-05-01

    Many diseases of the peripheral nervous system affect the function of Schwann cells. Recent developments in stem cell technology offer the opportunity to engineer stem cell derived glial cell populations that reveal essential phenotypic characteristics of Schwann cells including growth support and myelination of peripheral axons. Potential applications of these cells include its use as platform for human cell-based disease models as well as potential source for cell transplantation strategies. In this review we provide an update on the latest developments in engineering Schwann cells as diagnostic tools or for cell replacement therapies in peripheral neuropathic conditions. This article is part of a Special Issue entitled PSC and the brain. PMID:26529642

  13. Foot Care Knowledge and Practices and the Prevalence of Peripheral Neuropathy Among People with Diabetes Attending a Secondary Care Rural Hospital in Southern India

    PubMed Central

    George, Hanu; Rakesh, PS; Krishna, Manjunath; Alex, Reginald; Abraham, Vinod Joseph; George, Kuryan; Prasad, Jasmin H.

    2013-01-01

    Background: Diabetes mellitus is a multifaceted disease and foot ulceration is one of its most common complications. Poor foot care knowledge and practices are important risk factors for foot problems among people with diabetes. Aims: To assess the knowledge and practices regarding foot care and to estimate the proportion of people with peripheral neuropathy among people with diabetes. Settings and Design: The cross-sectional study was conducted in 212 consecutive diabetes patients attending the out-patient department of a rural secondary care hospital. Materials and Methods: A questionnaire which included demographic details, knowledge questionnaire, and Nottingham assessment of functional foot care was administered. The Michigan Neuropathy Screening Instrument was used to identify peripheral neuropathy. Statistical Analysis Used: Descriptive analysis with frequency distribution for knowledge and practice scores, univariate analysis, and multiple logistic regressions to find significant variables associated with good knowledge and practice scores. Results: About 75% had good knowledge score and 67% had good foot care practice score. Male gender (OR 2.36, 95% CI 1.16–4.79), poor education status (OR 2.40, 95% CI 1.19–4.28), and lesser duration of diabetes (OR 2.24, 95% CI 1.15–4.41) were significantly associated with poor knowledge on foot care. Poor knowledge was associated with poor foot care practices (OR 3.43, 95% CI 1.75–6.72). The prevalence of neuropathy was 47% (95% CI 40.14–53.85) and it was associated with longer duration of the disease (OR 2.18, 95% CI 1.18–4.04). Conclusion: There exist deficiencies in knowledge and practices regarding foot care. Male gender, low education, and lesser duration of diabetes are associated with poor knowledge scores. The prevalence of diabetic peripheral neuropathy is high. PMID:24479039

  14. Influence of GSTM1, GSTT1, and GSTP1 Polymorphisms on Type 2 Diabetes Mellitus and Diabetic Sensorimotor Peripheral Neuropathy Risk

    PubMed Central

    Stoian, Adina; Bănescu, Claudia; Bălaşa, Rodica Ioana; Moţăţăianu, Anca; Stoian, Mircea; Moldovan, Valeriu G.; Voidăzan, Septimiu; Dobreanu, Minodora

    2015-01-01

    Background and Aims. Diabetic neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM). Genetic susceptibility and oxidative stress may play a role in the appearance of T2DM and diabetic neuropathy. We investigated the relation between polymorphism in genes related to oxidative stress such as GSTM1, GSTT1, and GSTP1 and the presence of T2DM and diabetic neuropathy (DN). Methods. Samples were collected from 84 patients with T2DM (42 patients with DN and 42 patients without DN) and 98 healthy controls and genotyped by using polymerase chain reaction and restriction fragment length polymorphism method. Results. GSTP1 Ile105Val polymorphism was associated with the risk of developing T2DM (p = 0.05) but not with the risk of developing DN in diabetic cases. GSTM1 and GSTT1 gene polymorphisms were associated with neither the risk of developing T2DM nor the risk of DN occurrence in diabetic patients. No association was observed between the patients with T2DM and DSPN (diabetic sensorimotor peripheral neuropathy) and T2DM without DSPN regarding investigated polymorphism. Conclusion. Our data suggest that GSTP1 gene polymorphisms may contribute to the development of T2DM in Romanian population. GSTM1, GSTT1, and GSTP1 gene polymorphisms are not associated with susceptibility of developing diabetic neuropathy in T2DM patients. PMID:26435566

  15. Comparison of Nerve Excitability Testing, Nerve Conduction Velocity, and Behavioral Observations for Acrylamide Induced Peripheral Neuropathy

    EPA Science Inventory

    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...

  16. Oxaliplatin-Induced Peripheral Neuropathy via TRPA1 Stimulation in Mice Dorsal Root Ganglion Is Correlated with Aluminum Accumulation.

    PubMed

    Park, Jin-Hee; Chae, Jisook; Roh, Kangsan; Kil, Eui-Joon; Lee, Minji; Auh, Chung-Kyun; Lee, Myung-Ah; Yeom, Chang-Hwan; Lee, Sukchan

    2015-01-01

    Oxaliplatin is a platinum-based anticancer drug used to treat metastatic colorectal, breast, and lung cancers. While oxaliplatin kills cancer cells effectively, it exhibits several side effects of varying severity. Neuropathic pain is commonly experienced during treatment with oxaliplatin. Patients describe symptoms of paresthesias or dysesthesias that are triggered by cold (acute neuropathy), or as abnormal sensory or motor function (chronic neuropathy). In particular, we found that aluminum levels were relatively high in some cancer patients suffering from neuropathic pain based on clinical observations. Based on these findings, we hypothesized that aluminum accumulation in the dorsal root ganglion (DRG) in the course of oxaliplatin treatment exacerbates neuropathic pain. In mice injected with oxaliplatin (three cycles of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest), we detected cold allodynia using the acetone test, but not heat hyperalgesia using a hot plate. However, co-treatment with aluminum chloride (AlCl3∙6H2O; 7 mg/kg i.p. for 14 days: equivalent 0.78 mg/kg of elemental Al) and oxaliplatin (1 cycle of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest) synergistically induced cold allodynia as well as increased TRPAl mRNA and protein expression. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis showed a significant increase in aluminum concentrations in the DRG of mice treated with aluminum chloride and oxaliplatin compared to aluminum chloride alone. Similarly, in a mouse induced-tumor model, aluminum concentrations were increased in DRG tissue and tumor cells after oxaliplatin treatment. Taken together, these findings suggest that aluminum accumulation in the DRG may exacerbate neuropathic pain in oxaliplatin-treated mice. PMID:25928068

  17. Oxaliplatin-Induced Peripheral Neuropathy via TRPA1 Stimulation in Mice Dorsal Root Ganglion Is Correlated with Aluminum Accumulation

    PubMed Central

    Roh, Kangsan; Kil, Eui-Joon; Lee, Minji; Auh, Chung-Kyun; Lee, Myung-Ah; Yeom, Chang-Hwan; Lee, Sukchan

    2015-01-01

    Oxaliplatin is a platinum-based anticancer drug used to treat metastatic colorectal, breast, and lung cancers. While oxaliplatin kills cancer cells effectively, it exhibits several side effects of varying severity. Neuropathic pain is commonly experienced during treatment with oxaliplatin. Patients describe symptoms of paresthesias or dysesthesias that are triggered by cold (acute neuropathy), or as abnormal sensory or motor function (chronic neuropathy). In particular, we found that aluminum levels were relatively high in some cancer patients suffering from neuropathic pain based on clinical observations. Based on these findings, we hypothesized that aluminum accumulation in the dorsal root ganglion (DRG) in the course of oxaliplatin treatment exacerbates neuropathic pain. In mice injected with oxaliplatin (three cycles of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest), we detected cold allodynia using the acetone test, but not heat hyperalgesia using a hot plate. However, co-treatment with aluminum chloride (AlCl3∙6H2O; 7 mg/kg i.p. for 14 days: equivalent 0.78 mg/kg of elemental Al) and oxaliplatin (1 cycle of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest) synergistically induced cold allodynia as well as increased TRPAl mRNA and protein expression. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis showed a significant increase in aluminum concentrations in the DRG of mice treated with aluminum chloride and oxaliplatin compared to aluminum chloride alone. Similarly, in a mouse induced-tumor model, aluminum concentrations were increased in DRG tissue and tumor cells after oxaliplatin treatment. Taken together, these findings suggest that aluminum accumulation in the DRG may exacerbate neuropathic pain in oxaliplatin-treated mice. PMID:25928068

  18. Spinal astrocyte gap junction and glutamate transporter expression contributes to a rat model of bortezomib-induced peripheral neuropathy

    PubMed Central

    Robinson, Caleb R.; Dougherty, Patrick M.

    2014-01-01

    There is increasing evidence implicating astrocytes in multiple forms of chronic pain, as well as in the specific context of chemotherapy-induced peripheral neuropathy (CIPN). However, it is still unclear what the exact role of astrocytes may be in the context of CIPN. Findings in oxaliplatin and paclitaxel models have displayed altered expression of astrocytic gap junctions and glutamate transporters as means by which astrocytes may contribute to observed behavioral changes. The current study investigated whether these changes were also generalizable to the bortezomib CIPN. Changes in mechanical sensitivity were verified in bortezomib-treated animals, and these changes were prevented by co-treatment with a glial activation inhibitor (minocycline), a gap junction decoupler (carbenoxolone), and by a glutamate transporter upregulator (ceftriaxone). Immunohistochemistry data at day 30 in bortezomib-treated animals showed increases in expression of GFAP and connexin 43 but decrease in GLAST expression. These changes were prevented by co-treatment with minocycline. Follow-up Western blotting data showed a shift in connexin 43 from a non-phosphorylated state to a phosphorylated state, indicating increased trafficking of expressed connexin 43 to the cell membrane. These data suggest that increases in behavioral sensitivity to cutaneous stimuli may be tied to persistent synaptic glutamate resulting from increased calcium flow between spinal astrocytes. PMID:25446343

  19. Peripheral Nerve Ultrasonography in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy: Correlations with Clinical and Neurophysiological Data.

    PubMed

    Merola, Aristide; Rosso, Michela; Romagnolo, Alberto; Peci, Erdita; Cocito, Dario

    2016-01-01

    Objective. This cross-sectional study analyzes the pattern of ultrasound peripheral nerve alterations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) at different stages of functional disability. Material and Methods. 22 CIDP and 10 MMN patients and a group of 70 healthy controls were evaluated with an ultrasound scan of the median, ulnar, peroneal, tibial, and sural nerves. Results were correlated with clinical disability scales and nerve conduction studies. Results. Patients with intermediate functional impairment showed relatively larger cross-sectional areas than subjects with either a milder (p < 0.05) or more severe impairment (p < 0.05), both in CIDP and in MMN. In addition, MMN was associated with greater side-to-side intranerve variability (p < 0.05), while higher cross-sectional areas were observed in CIDP (p < 0.05) and in nerve segments with predominantly demyelinating features (p < 0.05). Higher CSA values were observed in nerves with demyelinating features versus axonal damage (p < 0.05 for CIDP; p < 0.05 for MMN). Discussion and Conclusions. Greater extent of quantitative and qualitative US alterations was observed in patients at intermediate versus higher functional disability and in nerves with demyelinating versus axonal damage. CIDP and MMN showed differential US aspects, with greater side-to-side intranerve variability in MMN and higher cross-sectional areas in CIDP. PMID:27313890

  20. Peripheral Nerve Ultrasonography in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy: Correlations with Clinical and Neurophysiological Data

    PubMed Central

    Merola, Aristide; Rosso, Michela; Romagnolo, Alberto; Peci, Erdita; Cocito, Dario

    2016-01-01

    Objective. This cross-sectional study analyzes the pattern of ultrasound peripheral nerve alterations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) at different stages of functional disability. Material and Methods. 22 CIDP and 10 MMN patients and a group of 70 healthy controls were evaluated with an ultrasound scan of the median, ulnar, peroneal, tibial, and sural nerves. Results were correlated with clinical disability scales and nerve conduction studies. Results. Patients with intermediate functional impairment showed relatively larger cross-sectional areas than subjects with either a milder (p < 0.05) or more severe impairment (p < 0.05), both in CIDP and in MMN. In addition, MMN was associated with greater side-to-side intranerve variability (p < 0.05), while higher cross-sectional areas were observed in CIDP (p < 0.05) and in nerve segments with predominantly demyelinating features (p < 0.05). Higher CSA values were observed in nerves with demyelinating features versus axonal damage (p < 0.05 for CIDP; p < 0.05 for MMN). Discussion and Conclusions. Greater extent of quantitative and qualitative US alterations was observed in patients at intermediate versus higher functional disability and in nerves with demyelinating versus axonal damage. CIDP and MMN showed differential US aspects, with greater side-to-side intranerve variability in MMN and higher cross-sectional areas in CIDP. PMID:27313890

  1. Evidence that nerve growth factor promotes the recovery of peripheral neuropathy induced in mice by cisplatin: behavioral, structural and biochemical analysis.

    PubMed

    Aloe, L; Manni, L; Properzi, F; De Santis, S; Fiore, M

    2000-12-28

    In this study we investigate the neurotoxic action of Cisplatin (6 micrograms/g body weight for 5 treatment cycles during 15 weeks with a total dose of 30 micrograms/g), an antitumor drug, and its effect on the level of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in peripheral tissues. We found that Cisplatin in adult rodents impairs peripheral sensory function and both sympathetic and sensory peripheral innervation as shown by the hot-plate response, catecholamine distribution and substance P immunoreactivity respectively. These changes are associated with decreased NGF in intestine, paws, and bladder while NGF increased in the spinal cord. Also BDNF decreased in bladder and paws and increased in spinal cord and intestine. To further investigate the role of NGF in the pathogenesis of Cisplatin-induced peripheral neuropathies a group of animals was injected with NGF (1 microgram/g every 4 days for 4 times) following Cisplatin treatment and evaluated for sensory function, sympathetic and sensory innervation and BDNF levels. Data demonstrated that exogenous NGF administration is able to restore biochemical, structural and functional changes induced by Cisplatin. These findings suggest that the reduction of NGF availability could be a cause of Cisplatin-induced peripheral neuropathies and that NGF exogenous administration could prevent or reduce Cisplatin neurotoxicity also in cancer patients, reducing the side effects of chemotherapy. PMID:11269929

  2. [Radiation-induced neuropathy].

    PubMed

    Kolak, Agnieszka; Starosławska, Elzbieta; Kieszko, Dariusz; Cisek, Paweł; Patyra, Krzysztof Ireneusz; Surdyka, Dariusz; Dobrzyńska-Rutkowska, Aneta; Łopacka-Szatan, Karolina; Burdan, Franciszek

    2013-12-01

    Radiation-induced neuropathy is commonly observed among oncological patients. Radiation can affect the nervous tissue directly or indirectly by inducing vasculopathy or dysfunction of internal organs. Symptoms may be mild and reversible (e.g., pain, nausea, vomiting, fever, drowsiness, fatigue, paresthesia) or life-threatening (cerebral oedema, increased intracranial pressure, seizures). Such complications are clinically divided into peripheral (plexopathies, neuropathies of spinal and cranial nerves) and central neuropathy (myelopathy, encephalopathy, cognitive impairment). The degree of neuronal damages primarily depends on the total and fractional radiation dose and applied therapeutic methods. The conformal and megavoltage radiotherapy seems to be the safeties ones. Diagnostic protocol includes physical examination, imaging (in particular magnetic resonance), electromyography, nerve conduction study and sometimes histological examination. Prevention and early detection of neurological complications are necessary in order to prevent a permanent dysfunction of the nervous system. Presently their treatment is mostly symptomatic, but in same cases a surgical intervention is required. An experimental and clinical data indicates some effectiveness of different neuroprotective agents (e.g. anticoagulants, vitamin E, hyperbaric oxygen, pentoxifylline, bevacizumab, methylphenidate, donepezil), which should be administered before and/or during radiotherapy. PMID:24490474

  3. Hereditary neuropathy.

    PubMed

    Heidenreich, Wayne F

    2010-01-01

    A 58-year-old male presented with a history of slowly progressive bilateral hand weakness manifested by decreased grip strength and pinch strength associated with some pain in the first metacarpal-carpal joints with atrophy of the muscles of the web space. An evaluation based on history, physical exam, and judicious diagnostic testing yielded a finding of motor and sensory peripheral polyneuropathy and a working diagnosis of hereditary nerve pressure palsy syndrome (HNPP) or hereditary neuropathy with liability to pressure palsies. The clinical findings and diagnostic tests for sensory and motor peripheral neuropathy are discussed. The case details over time, hereditary features, and the natural history of this disorder lead to a favorable clinical and insurance medicine prognosis. PMID:21290997

  4. Late-onset Tay-Sachs disease: the spectrum of peripheral neuropathy in 30 affected patients.

    PubMed

    Shapiro, Barbara E; Logigian, Eric L; Kolodny, Edwin H; Pastores, Gregory M

    2008-08-01

    Late-onset Tay-Sachs (LOTS) disease is a chronic, progressive, lysosomal storage disorder caused by a partial deficiency of beta-hexosaminidase A (HEXA) activity. Deficient levels of HEXA result in the intracellular accumulation of GM2-ganglioside, resulting in toxicity to nerve cells. Clinical manifestations primarily involve the central nervous system (CNS) and lower motor neurons, and include ataxia, weakness, spasticity, dysarthria, dysphagia, dystonia, seizures, psychosis, mania, depression, and cognitive decline. The prevalence of peripheral nervous system (PNS) involvement in LOTS has not been well documented, but it has traditionally been thought to be very low. We examined a cohort of 30 patients with LOTS who underwent clinical and electrophysiologic examination, and found evidence of a predominantly axon loss polyneuropathy affecting distal nerve segments in the lower and upper extremities in eight patients (27%). PMID:18642377

  5. Clomipramine vs desipramine vs placebo in the treatment of diabetic neuropathy symptoms. A double-blind cross-over study.

    PubMed Central

    Sindrup, S H; Gram, L F; Skjold, T; Grodum, E; Brøsen, K; Beck-Nielsen, H

    1990-01-01

    1. The effect of clomipramine and desipramine on diabetic neuropathy symptoms was examined in a double-blind, randomised, placebo controlled, cross-over study for 2 + 2 + 2 weeks. Drug doses were adjusted according to the sparteine phenotype, i.e. extensive metabolisers were treated with 75 mg clomipramine day-1 and 200 mg desipramine day-1 whereas poor metabolisers were treated with 50 mg day-1 of both drugs. Nineteen patients completed the study. 2. Plasma concentration of clomipramine plus desmethylclomipramine was 70-510 nM in extensive metabolisers, vs 590 and 750 nM in two poor metabolisers. Desipramine levels were 130-910 nM, vs 860 and 880 nM. 3. Both clomipramine and desipramine significantly reduced the symptoms of neuropathy as measured by observer- and self rating in comparison with placebo. Clomipramine tended to be more efficacious than desipramine. Patients with a weak or absent response on clomipramine had lower plasma concentrations (clomipramine plus desmethyl-clomipramine less than 200 nM) than patients with a better response. For desipramine a relationship between plasma concentration and effect was not established. 4. Side effect ratings did not differ for clomipramine and desipramine and on both drugs three patients withdrew due to side effects. 5. Compared with earlier results obtained with imipramine dosed on the basis of plasma level monitoring, clomipramine and desipramine on fixed doses appeared less efficacious whereas the side effect profiles were the same. At least for clomipramine, appropriate dose adjustment on the basis of plasma level monitoring may increase the efficacy. PMID:2271367

  6. Evaluation of sural nerve automated nerve conduction study in the diagnosis of peripheral neuropathy in patients with type 2 diabetes mellitus

    PubMed Central

    Chatzikosma, Georgia; Pafili, Kalliopi; Demetriou, Maria; Vadikolias, Konstantinos; Maltezos, Efstratios

    2016-01-01

    Introduction New tests for improved diagnosis of diabetic peripheral neuropathy (DPN) are useful. Material and methods We evaluated the utility of automated nerve conduction study (NCS) of the sural nerve with a new portable device for the diagnosis of DPN in patients with type 2 diabetes mellitus (T2DM). This study included 114 T2DM patients (58 men) with mean age 64.60 ±8.61 years. Exclusion criteria were B12 depletion, alcohol abuse and other causes of peripheral neuropathy. The reference method was the Neuropathy Disability Score (NDS) with a threshold NDS ≥ 3. Sural nerve automated NCS was carried out with the portable NC-stat DPNCheck device. Sensory nerve conduction velocity and sensory nerve action potential amplitude were measured bilaterally. Automated NCS was considered abnormal when ≥ 1 of the two aforementioned neurophysiological parameters was abnormal in at least one leg. Results Examination with NC-stat DPNCheck exhibited 90.48% sensitivity, 86.11% specificity, 79.17% positive predictive value (PPV) and 93.94% negative predictive value (NPV). The positive likelihood ratio (LR+) was 6.51 and the negative likelihood ratio (LR–) was 0.11. Conclusions Sural nerve automated NCS with the NC-stat DPNCheck device exhibits high sensitivity and specificity for the diagnosis of DPN in T2DM. PMID:27186185

  7. Inherited neuropathies.

    PubMed

    Chance, P F; Reilly, M

    1994-10-01

    Charcot-Marie-Tooth neuropathy (CMT) type 1 is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), the X chromosome (CMTX), and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-Mb duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (P0) gene. The molecular defect in CMT1C is unknown. CMTX is associated with mutations in the connexin 32 gene. CMT2 is an axonal neuropathy of undetermined cause. One form of CMT2 maps to chromosome 1p36 (CMT2A). Dejerine-Sottas disease is a severe, infantile-onset demyelinating polyneuropathy that may be associated with point mutations in either the PMP22 gene or the P0 gene. Hereditary neuropathy with liability to pressure palsies (HNPP) is a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and may result from reduced expression of the PMP22 gene. Most examples of CMT1A and HNPP are reciprocal duplication or deletion syndromes originating from unequal crossover during germ cell meiosis. Familial amyloid polyneuropathy (FAP) is an autosomal dominant disorder that classically presents with a sensory peripheral neuropathy and early autonomic involvement. Transthyretin (TTR) is the most common constituent amyloid fibril protein deposited in FAP, and there are now 28 point mutations in the TTR gene described in TTR-related FAP. Liver transplantation looks promising as a treatment for TTR-related FAP. PMID:7804455

  8. Genome-wide association studies for taxane-induced peripheral neuropathy (TIPN) in ECOG-5103 and ECOG-1199

    PubMed Central

    Shen, Fei; Miller, Kathy D.; Flockhart, David A.; Jiang, Guanglong; Vance, Gail; Gardner, Laura; Vatta, Matteo; Bai, Shaochun; Lai, Dongbing; Koller, Daniel; Zhao, Fengmin; O'Neill, Anne; Smith, Mary Lou; Railey, Elda; White, Carol; Partridge, Ann; Sparano, Joseph; Davidson, Nancy E.

    2015-01-01

    Purpose Taxane induced peripheral neuropathy (TIPN) is an important survivorship issue for many cancer patients. Currently, there are no clinically implemented biomarkers to predict which patients might be at increased risk for TIPN. We present a comprehensive approach to identification of genetic variants to predict TIPN. Experimental Design We performed a genome wide association study (GWAS) in 3431 patients from the phase III adjuvant breast cancer trial, ECOG-5103 to compare genotypes with TIPN. We performed candidate validation of top SNPs for TIPN in another phase III adjuvant breast cancer trial, ECOG-1199. Results When evaluating for Grade 3-4 TIPN, 120 SNPs had a p-value <10−4 from patients of European descent (EA) in ECOG-5103. 30 candidate SNPs were subsequently tested in ECOG-1199 and SNP rs3125923 was found to be significantly associated with Grade 3-4 TIPN (p=1.7×10−3; OR=1.8). Race was also a major predictor of TIPN, with patients of African descent (AA) experiencing increased risk of Grade 2-4 TIPN (HR=2.1; p=5.6×10−16) and Grade 3-4 TIPN (HR=2.6; p=1.1×10−11) compared with others. A SNP in FCAMR, rs1856746, had a trend toward an association with Grade 2-4 TIPN in AA patients from the GWAS in ECOG-5103 (OR=5.5; p=1.6×10−7). Conclusion rs3125923 represents a validated SNP to predict Grade 3-4 TIPN. Genetically determined AA race represents the most significant predictor of TIPN. PMID:26138065

  9. Clinical utility of a DNA probe to 17p11.2 in screening of patients with a peripheral neuropathy

    SciTech Connect

    Blancato, J.; Precht, K.; Meck, J.

    1994-09-01

    We assessed the usefulness of in situ hybridization with a DNA probe to the area of chromosome 17 at p11.2 as a diagnostic tool for screening for Charcot Marte Tooth 1A (CMT 1A). In situ hybridization with a probe to 17p11.2 was performed on fixed lymphocytes from the following groups of individuals: (1) normal controls; (2) patients evoking a strong clinical suspicion of CMT 1A; and (3) 3 families with an apparent autosomal dominant peripheral neuropathy of unknown diagnoses. Group 2 patients had evidence of demyelination as defined by nerve conduction of less that 50% of the normal mean or terminal latency greater than 50% of the normal mean in conduction studies. Analysis of interphase cells hybridized with a cosmid DNA probe to 17p11.2 requires inclusion of a normal control with each trial and masked observer. Due to the size of the target DNA and the nature of the centromeric heterochromatin, the scoring of this probe is more subjective than centromere probes. For example, if the two 17 chromosomes are decondensed as in interphase, two tandem signals may be visualized as one. Results from duplication positive patients demonstrate a large proportion of cells with two closely aligned, but separate, signals with an additional single signal. Normal results demonstrate a majority of cells with two separate signals representing both normal homologues. None of the 3 families with questionable diagnosis revealed a duplication at the region, reinforcing our belief that a clinical diagnosis is the most discriminating tool available for diagnosis of CMT 1A. We concur with Boylan that molecular analysis for CMT 1A is useful for establishing a diagnosis of CMT 1A, but is not a primary differential diagnostic test. The yield in screening patients without physiologic evidence of demyelination is likely to be low. We further find that the use of in situ hybridization is a simple method of performing the duplication analysis.

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

    PubMed

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

    2006-01-01

    The medical records of 2239 patients (mean age=73 years) with established peripheral neuropathy (PN) were examined to determine whether treatment with MIRE was, in fact, associated with increased foot sensitivity to the Semmes Weinstein monofilament (SWM) 5.07 and a reduction in neuropathic pain. The PN in 1395 of these patients (62%) was due to diabetes. Prior to treatment with MIRE, of the 10 tested sites (5 on each foot), 7.1+/-2.9 were insensitive to the SWM 5.07, and 2078 patients (93%) exhibited loss of protective sensation defined by Medicare as a loss of sensation at two or more sites on either foot. After treatment, the number of insensate sites on both feet decreased to 2.4+/-2.6, an improvement of 66%. Of the 2078 (93%) patients initially presenting with loss of protective sensation, 1106 (53%) no longer had loss of protective sensation after treatment (P<.0001); 1563 patients (70%) also exhibited neuropathic pain in addition to sensory impairment. Prior to treatment with MIRE, pain measured on the 11-point visual analogue scale (VAS) was 7.2+/-2.2 points, despite the use of a variety of pain-relieving therapeutic agents. After treatment with MIRE, pain was reduced by 4.8+/-2.4 points, a 67% reduction. Therefore, MIRE appears to be associated with significant clinical improvement in foot sensation and, simultaneously, a reduction in neuropathic pain in a large cohort of primarily Medicare aged, community-dwelling patients, initially diagnosed with PN. The quality of life associated with these two outcomes cannot be underappreciated. PMID:16504836

  11. Predictors of Barefoot Plantar Pressure during Walking in Patients with Diabetes, Peripheral Neuropathy and a History of Ulceration

    PubMed Central

    Barn, Ruth; Waaijman, Roelof; Nollet, Frans; Woodburn, James; Bus, Sicco A.

    2015-01-01

    Objective 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. Methods 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. Results 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). Conclusion 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. PMID:25647421

  12. Pes cavus and hereditary neuropathies: when a relationship should be suspected.

    PubMed

    Piazza, S; Ricci, G; Caldarazzo Ienco, E; Carlesi, C; Volpi, L; Siciliano, G; Mancuso, M

    2010-12-01

    The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of diseases of the peripheral nervous system. Foot deformities, including the common pes cavus, but also hammer toes and twisting of the ankle, are frequently present in patients with hereditary peripheral neuropathy, and often represent one of the first signs of the disease. Pes cavus in hereditary peripheral neuropathies is caused by imbalance between the intrinsic muscles of the foot and the muscles of the leg. Accurate clinical evaluation in patients with pes cavus is necessary to exclude or confirm the presence of peripheral neuropathy. Hereditary peripheral neuropathies should be suspected in those cases with bilateral foot deformities, in the presence of family history for pes cavus and/or gait impairment, and in the presence of neurological symptoms or signs, such as distal muscle hypotrophy of limbs. Herein, we review the hereditary peripheral neuropathies in which pes cavus plays a key role as a "spy sign," discussing the clinical and molecular features of these disorders to highlight the importance of pes cavus as a helpful clinical sign in these rare diseases. PMID:20963465

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

    PubMed

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

    2015-03-01

    Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome, frequently affects the peripheral nervous system. We conducted a multicenter, double-blind, three-arm treatment period, randomized, pre-post trial to assess the efficacy of intravenous immunoglobulin (IVIg) administration for residual peripheral neuropathy in patients with EGPA that is in remission, indicated by laboratory indices. Twenty-three patients were randomly assigned into three groups, in which the timing of IVIg and placebo administration was different. Each group received one course of intervention and two courses of placebo at 2-week intervals. Treatment effects were assessed every 2 weeks for 8 weeks. The primary outcome measure, the amount of change in the manual muscle testing sum score 2 weeks after IVIg administration, significantly increased (p = 0.002). The results over time suggested that this effect continued until the last assessment was done 8 weeks later. The number of muscles with manual muscle testing scores of three or less (p = 0.004) and the neuropathic pain scores represented by the visual analogue scale (p = 0.005) also improved significantly 2 weeks after IVIg administration. This study indicates that IVIg treatment for EGPA patients with residual peripheral neuropathy should be considered even when laboratory indices suggest remission of the disease. PMID:25577176

  14. Effect of levetiracetam versus gabapentin on peripheral neuropathy and sciatic degeneration in streptozotocin-diabetic mice: Influence on spinal microglia and astrocytes.

    PubMed

    Reda, Heba M; Zaitone, Sawsan A; Moustafa, Yasser M

    2016-01-15

    Peripheral diabetic neuropathy develops in diabetic patients. The current study tested the antiallodynic and antihyperalgesic effects of the anticonvulsant drug, levetiracetam compared with the standard drug, gabapentin, in a model of streptozotocin-induced peripheral diabetic neuropathy. Male albino mice were injected intraperitoneally with streptozotocin (40mg/kg) for five consecutive days to induce type 1 diabetes mellitus. After development of peripheral diabetic neuropathy, mice were then treated orally with 10 doses of levetiracetam or gabapentin (or vehicle). The effect of multiple doses of levetiracetam on the histopathology of sciatic nerve and spinal cord was tested. Furthermore, the effect of levetiracetam on the spinal expression of microglia and astrocytes was examined in comparison with gabapentin. Results indicated that the highest dose of levetiracetam and all doses of gabapentin increased the withdrawal threshold in von Frey test. Furthermore, all doses of levetiracetam and gabapentin prolonged the reaction time exhibited by diabetic mice tested in hot plate test. Both drugs provided protection for the sciatic nerve and the spinal cord. In addition, levetiracetam (20 and 40mg/kg) decreased spinal immunostaining for CD11b (microglia marker) and glial fibrillary acidic protein (GFAP, astrocytes marker) however; the high dose of gabapentin (40mg/kg) reduced the spinal immunostaining for GFAP only. In conclusion, levetiracetam produced antiallodynic and antihyperalgesic effect in diabetic mice with favorable effects on sciatic nerve and spinal cord that were accompanied by downregulation of the spinal expression of microglia and astrocytes. Thus, levetiracetam may have promise in alleviating neuropathic pain in diabetic patients. PMID:26712375

  15. Hereditary Neuropathies

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Hereditary Neuropathies Information Page Synonym(s): Neuropathy - Hereditary Table of Contents ( ... and Information Publicaciones en Español What are Hereditary Neuropathies? Hereditary neuropathies are a group of inherited disorders ...

  16. Novel single base-pair deletion in exon 1 of XK gene leading to McLeod syndrome with chorea, muscle wasting, peripheral neuropathy, acanthocytosis and haemolysis.

    PubMed

    Wiethoff, Sarah; Xiromerisiou, Georgia; Bettencourt, Conceição; Kioumi, Anna; Tsiptsios, Iakovos; Tychalas, Athanasios; Evaggelia, Markousi; George, Kaltsounis; Makris, Vasileios; Hardy, John; Houlden, Henry

    2014-04-15

    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. PMID:24529944

  17. Occupational Exposure to Swine, Poultry, and Cattle and Antibody Biomarkers of Campylobacter jejuni Exposure and Autoimmune Peripheral Neuropathy

    PubMed Central

    Vegosen, Leora; Breysse, Patrick N.; Agnew, Jacqueline; Gray, Gregory C.; Nachamkin, Irving; Sheikh, Kazim; Kamel, Freya; Silbergeld, Ellen

    2015-01-01

    Introduction 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. Methods 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. Results 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. Conclusions 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

  18. Cardiovascular Risk Factors Increase the Risks of Diabetic Peripheral Neuropathy in Patients With Type 2 Diabetes Mellitus

    PubMed Central

    Yang, Chun-Pai; Lin, Cheng-Chieh; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Hwang, Kai-Lin; Yang, Sing-Yu; Chen, Hsuan-Ju; Li, Tsai-Chung

    2015-01-01

    Abstract This study aimed to examine whether poor glycemic control, measured by glycated hemoglobin A1C (HbA1c) and other cardiovascular risk factors, can predict diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (DM). Patients aged ≥30 years with type 2 DM, enrolled in the National Diabetes Care Management Program, and free of DPN (n = 37,375) in the period 2002 to 2004 were included and followed up until 2011. The related factors were analyzed using Cox proportional hazards regression models. For an average follow-up of 7.00 years, 8379 cases of DPN were identified, with a crude incidence rate of 32.04/1000 person-years. After multivariate adjustment, patients with HbA1c levels 7 to 8%, 8 to 9%, 9 to 10%, and ≥10% exhibited higher risk of DPN (adjusted HR: 1.11 [1.04–1.20], 1.30 [1.21–1.40], 1.32 [1.22–1.43], and 1.62 [1.51–1.74], respectively) compared with patients with HbA1c level 6 to 7%. There was a significant linear trend in DPN incidence with increasing HbA1c (P < 0.001) and significant HRs of DPN for patients with HbA1c level ≥7%, blood pressure ≥130/85 mm Hg, triglycerides (TG) ≥150 mg/dL, high density of lipoprotein-cholesterol (HDL-C) <40 mg/dL in males and <50 mg/dL in females, low density of lipoprotein-cholesterol (LDL-C) ≥100 mg/dL, and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Patients with type 2 DM and HbA1c ≥7.0% exhibit increased risk of DPN, demonstrating a linear relationship. The incidence of DPN is also associated with poor glucose control and cardiovascular risk factors like hypertension, hyper-triglyceridemia, low HDL-C, high LDL-C, and decreased eGFR. PMID:26496307

  19. Peptidergic intraepidermal nerve fibers in the skin contribute to the neuropathic pain in paclitaxel-induced peripheral neuropathy.

    PubMed

    Ko, Miau-Hwa; Hu, Ming-E; Hsieh, Yu-Lin; Lan, Chyn-Tair; Tseng, To-Jung

    2014-06-01

    Paclitaxel in chemotherapy-induced peripheral neuropathy (CIPN) is predominantly with a dose-limiting effect on neuropathic pain in clinical strategy. In the present study, the relationship between the neuropathic pain and nerve degeneration in paclitaxel CIPN was investigated. Adult male Sprague-Dawley (SD) rats were divided into three paclitaxel groups (0.5, 1.0, 2.0mg/kg) and a vehicle group with four intraperitoneal (i.p.) injections on alternating days. Our results demonstrated that the paclitaxel groups significantly exhibited the reductions of thermal hyperalgesia and mechanical allodynia. The neurotoxicity of paclitaxel conveyed the degeneration of intraepidermal nerve fibers (IENFs) in hindpaw glabrous skin. Nevertheless, the influence of paclitaxel to the peptidergic IENFs are even unknown. The skin innervation of protein gene product 9.5 (PGP 9.5)-immunoreactive (IR) IENFs in paclitaxel groups revealed the decreasing levels of density (73.54±0.72%, 63.17±1.77%, 61.79±2.68%, respectively; vs. vehicle group, p<0.05) throughout the entire experimental period. Additionally, the diminishing levels of density for peptidergic substance P (SP)-IR IENFs in paclitaxel groups were significantly shown (48.84±1.74%, 30.02±1.69%, 30.14±0.37%, respectively; vs. vehicle group, p<0.05). On the contrary, the density for peptidergic calcitonin gene-related peptide (CGRP)-IR IENFs in paclitaxel groups were revealed the similar decreasing levels (82.75±0.91%, 84.34±3.20%, 81.99±0.25%, respectively; vs. vehicle group, p<0.05). Linear regression analyses exhibited that densities of IENFs for PGP 9.5, SP, CGRP were correlated with withdrawal latencies (r(2)=0.77, p<0.0001; r(2)=0.75, p<0.0001; r(2)=0.28, p=0.0001, respectively) and mechanical thresholds (r(2)=0.43, p<0.0001; r(2)=0.73, p<0.0001; r(2)=0.40, p<0.0001, respectively). Therefore, the present results suggested that the development of neuropathic pain following paclitaxel injection induced the progressive

  20. Painful neuropathies: the emerging role of sodium channelopathies.

    PubMed

    Brouwer, Brigitte A; Merkies, Ingemar S J; Gerrits, Monique M; Waxman, Stephen G; Hoeijmakers, Janneke G J; Faber, Catharina G

    2014-06-01

    Pain is a frequent debilitating feature reported in peripheral neuropathies with involvement of small nerve (Aδ and C) fibers. Voltage-gated sodium channels are responsible for the generation and conduction of action potentials in the peripheral nociceptive neuronal pathway where NaV 1.7, NaV 1.8, and NaV 1.9 sodium channels (encoded by SCN9A, SCN10A, and SCN11A) are preferentially expressed. The human genetic pain conditions inherited erythromelalgia and paroxysmal extreme pain disorder were the first to be linked to gain-of-function SCN9A mutations. Recent studies have expanded this spectrum with gain-of-function SCN9A mutations in patients with small fiber neuropathy and in a new syndrome of pain, dysautonomia, and small hands and small feet (acromesomelia). In addition, painful neuropathies have been recently linked to SCN10A mutations. Patch-clamp studies have shown that the effect of SCN9A mutations is dependent upon the cell-type background. The functional effects of a mutation in dorsal root ganglion (DRG) neurons and sympathetic neuron cells may differ per mutation, reflecting the pattern of expression of autonomic symptoms in patients with painful neuropathies who carry the mutation in question. Peripheral neuropathies may not always be length-dependent, as demonstrated in patients with initial facial and scalp pain symptoms with SCN9A mutations showing hyperexcitability in both trigeminal ganglion and DRG neurons. There is some evidence suggesting that gain-of-function SCN9A mutations can lead to degeneration of peripheral axons. This review will focus on the emerging role of sodium channelopathies in painful peripheral neuropathies, which could serve as a basis for novel therapeutic strategies. PMID:25250524

  1. CaV3.2 T-type calcium channels in peripheral sensory neurons are important for mibefradil-induced reversal of hyperalgesia and allodynia in rats with painful diabetic neuropathy.

    PubMed

    Obradovic, Aleksandar Lj; Hwang, Sung Mi; Scarpa, Joseph; Hong, Sung Jun; Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

    2014-01-01

    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. PMID:24705276

  2. Contralateral ulnar neuropathy following total hip replacement and intraoperative positioning.

    PubMed

    O'Brien, S; Bennett, D; Spence, D J; Mawhinney, I; Beverland, D E

    2016-05-01

    Peripheral neuropathy is a rare but important complication of total hip arthroplasty (THA) and has previously been reported in the ipsilateral arm and associated with inflammatory arthritis. The results of 7004 primary hip arthroplasties performed between January 1993 and February 2009 were retrospectively reviewed to identify patients who reported ulnar neuropathy symptoms, with ten patients identified at mean follow-up of 57 months (range = 3-195 months). Eight patients experienced unilateral ulnar nerve symptoms in the contralateral upper limb post-surgery, one patient experienced symptoms in the ipsilateral upper limb and one patient experienced symptoms in both upper limbs. The incidence of post-THA ulnar neuropathy was 0.14%. All patients had a pre-operative diagnosis of osteoarthritis and none had diabetes, a previous history of neuropathy or inflammatory arthritis. All operations were primary arthroplasties and were performed under the care of a single surgeon in a single centre. Two of the ten patients (20%) had a general anaesthetic. The pattern of symptoms reported, i.e. mainly unilateral affecting the contralateral side with variable resolution, contrasts with previous studies and suggests that intraoperative patient positioning may be an important factor influencing ulnar neuropathy following THA. Attention to support and positioning of the contralateral arm may help reduce the incidence of this complication. PMID:26589446

  3. Fibered fluorescence microscopy (FFM) of intra epidermal nerve fibers--translational marker for peripheral neuropathies in preclinical research: processing and analysis of the data

    NASA Astrophysics Data System (ADS)

    Cornelissen, Frans; De Backer, Steve; Lemeire, Jan; Torfs, Berf; Nuydens, Rony; Meert, Theo; Schelkens, Peter; Scheunders, Paul

    2008-08-01

    Peripheral neuropathy can be caused by diabetes or AIDS or be a side-effect of chemotherapy. Fibered Fluorescence Microscopy (FFM) is a recently developed imaging modality using a fiber optic probe connected to a laser scanning unit. It allows for in-vivo scanning of small animal subjects by moving the probe along the tissue surface. In preclinical research, FFM enables non-invasive, longitudinal in vivo assessment of intra epidermal nerve fibre density in various models for peripheral neuropathies. By moving the probe, FFM allows visualization of larger surfaces, since, during the movement, images are continuously captured, allowing to acquire an area larger then the field of view of the probe. For analysis purposes, we need to obtain a single static image from the multiple overlapping frames. We introduce a mosaicing procedure for this kind of video sequence. Construction of mosaic images with sub-pixel alignment is indispensable and must be integrated into a global consistent image aligning. An additional motivation for the mosaicing is the use of overlapping redundant information to improve the signal to noise ratio of the acquisition, because the individual frames tend to have both high noise levels and intensity inhomogeneities. For longitudinal analysis, mosaics captured at different times must be aligned as well. For alignment, global correlation-based matching is compared with interest point matching. Use of algorithms working on multiple CPU's (parallel processor/cluster/grid) is imperative for use in a screening model.

  4. Phase 1/2 open-label dose-escalation study of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with painful diabetic peripheral neuropathy.

    PubMed

    Ajroud-Driss, Senda; Christiansen, Mark; Allen, Jeffrey A; Kessler, John A

    2013-06-01

    This study aimed to evaluate the safety and preliminary efficacy of intramuscular injections of plasmid DNA (VM202) expressing two isoforms of hepatocyte growth factor (HGF) in subjects with painful diabetic peripheral neuropathy (PDPN). Twelve patients in three cohorts (4, 8, and 16 mg) received two sets of VM202 injections separated by two weeks. Safety and tolerability were evaluated and the visual analog scale (VAS), the short form McGill questionnaire (SF-MPQ), and the brief pain inventory for patients with diabetic peripheral neuropathy (BPI-DPN) measured pain level throughout 12 months after treatment. No serious adverse events (AEs) were observed. The mean VAS was reduced from baseline by 47.2% (P = 0.002) at 6 months and by 44.1% (P = 0.005) at 12 months after treatment. The VAS scores for the 4, 8, and 16 mg dose cohorts at 6 months follow-up decreased in a dose-responsive manner, by 21% (P = 0.971), 53% (P = 0.014), and 62% (P = 0.001), respectively. The results with the BPI-DPN and SF-MPQ showed patterns similar to the VAS scores. In conclusion, VM202 treatment appeared to be safe, well tolerated, and sufficient to provide long term symptomatic relief and improvement in the quality of life in patients with PDPN. PMID:23609019

  5. Phase 1/2 Open-label Dose-escalation Study of Plasmid DNA Expressing Two Isoforms of Hepatocyte Growth Factor in Patients With Painful Diabetic Peripheral Neuropathy

    PubMed Central

    Ajroud-Driss, Senda; Christiansen, Mark; Allen, Jeffrey A; Kessler, John A

    2013-01-01

    This study aimed to evaluate the safety and preliminary efficacy of intramuscular injections of plasmid DNA (VM202) expressing two isoforms of hepatocyte growth factor (HGF) in subjects with painful diabetic peripheral neuropathy (PDPN). Twelve patients in three cohorts (4, 8, and 16 mg) received two sets of VM202 injections separated by two weeks. Safety and tolerability were evaluated and the visual analog scale (VAS), the short form McGill questionnaire (SF-MPQ), and the brief pain inventory for patients with diabetic peripheral neuropathy (BPI-DPN) measured pain level throughout 12 months after treatment. No serious adverse events (AEs) were observed. The mean VAS was reduced from baseline by 47.2% (P = 0.002) at 6 months and by 44.1% (P = 0.005) at 12 months after treatment. The VAS scores for the 4, 8, and 16 mg dose cohorts at 6 months follow-up decreased in a dose–responsive manner, by 21% (P = 0.971), 53% (P = 0.014), and 62% (P = 0.001), respectively. The results with the BPI-DPN and SF-MPQ showed patterns similar to the VAS scores. In conclusion, VM202 treatment appeared to be safe, well tolerated, and sufficient to provide long term symptomatic relief and improvement in the quality of life in patients with PDPN. PMID:23609019

  6. The gene responsible for a severe form of peripheral neuropathy and agenesis of the corpus callosum maps to chromosome 15q

    SciTech Connect

    Casaubon, L.K.; Melanson, M.; Marineau, C. |

    1996-01-01

    Peripheral neuropathy with or without agenesis of the corpus callosum (ACCPN) is a devastating neurodegenerative disorder that is transmitted as an autosomal recessive trait. Genealogical studies in a large number of affected French Canadian individuals suggest that ACCPN results from a single founder mutation. A genomewide search using 120 microsatellite DNA markers in 14 French Canadian families allowed the mapping of the ACCPN gene to a 5-cM region on chromosome 15q13-q15 that is flanked by markers D15S1040 and D15S118. A maximum two-point LOD score of 11.1 was obtained with the marker D15S971 at a recombination fraction of 0. Haplotype analysis and linkage disequilibrium support a founder effect. These findings are the first step in the identification of the gene responsible for ACCPN, which may shed some light on the numerous conditions associated with progressive peripheral neuropathy or agenesis of the corpus callosum. 28 refs., 2 figs., 3 tabs.

  7. Involvement of high mobility group box 1 in the development and maintenance of chemotherapy-induced peripheral neuropathy in rats.

    PubMed

    Nishida, Takeshi; Tsubota, Maho; Kawaishi, Yudai; Yamanishi, Hiroki; Kamitani, Natsuki; Sekiguchi, Fumiko; Ishikura, Hiroyasu; Liu, Keyue; Nishibori, Masahiro; Kawabata, Atsufumi

    2016-07-15

    Given that high mobility group box 1 (HMGB1), a nuclear protein, once released to the extracellular space, promotes nociception, we asked if inactivation of HMGB1 prevents or reverses chemotherapy-induced painful neuropathy in rats and also examined possible involvement of Toll-like receptor 4 (TLR4) and the receptor for advanced glycation endproduct (RAGE), known as targets for HMGB1. Painful neuropathy was produced by repeated i.p. administration of paclitaxel or vincristine in rats. Nociceptive threshold was determined by the paw pressure method and/or von Frey test in the hindpaw. Tissue protein levels were determined by immunoblotting. Repeated i.p. administration of the anti-HMGB1-neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, prevented the development of hyperalgesia and/or allodynia induced by paclitaxel or vincristine in rats. A single i.p. or intraplantar (i.pl.) administration of the antibody or rhsTM reversed the chemotherapy-induced neuropathy. A single i.pl. administration of a TLR4 antagonist or low molecular weight heparin, known to inhibit RAGE, attenuated the hyperalgesia caused by i.pl. HMGB1 and also the chemotherapy-induced painful neuropathy. Paclitaxel or vincristine treatment significantly decreased protein levels of HMGB1 in the dorsal root ganglia, but not sciatic nerves. HMGB1 thus participates in both development and maintenance of chemotherapy-induced painful neuropathy, in part through RAGE and TLR4. HMGB1 inactivation is considered useful to prevent and treat the chemotherapy-induced painful neuropathy. PMID:27474498

  8. Metabolic neuropathies and myopathies.

    PubMed

    D'Amico, Adele; Bertini, Enrico

    2013-01-01

    Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are β-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. On the other hand, lysosomal (mucopolysaccharidosis, Gaucher and Fabry diseases), mitochondriopathic (mitochondrial or nuclear mutations or mDNA depletion), peroxisomal (adrenomyeloneuropathy, Refsum disease, sterol carrier protein-2 deficiency, cerebrotendinous xanthomatosis, α-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are exercise intolerance with myalgias, cramps and recurrent myoglobinuria or limb weakness associated with elevation of serum creatine kinase. Carnitine palmitoyl transferase deficiency, followed by acid maltase deficiency, and lipin deficiency, are the most common cause of isolated rhabdomyolysis. Metabolic myopathies are frequently associated to extra-neuromuscular disorders particularly involving the heart, liver, brain, retina, skin, and kidney. PMID:23622366

  9. Diabetic neuropathy: electrophysiological and morphological study of peripheral nerve degeneration and regeneration in transgenic mice that express IFNbeta in beta cells.

    PubMed

    Serafín, Anna; Molín, Jessica; Márquez, Merce; Blasco, Ester; Vidal, Enric; Foradada, Laia; Añor, Sonia; Rabanal, Rosa M; Fondevila, Dolors; Bosch, Fàtima; Pumarola, Martí

    2010-05-01

    Diabetic neuropathy is one of the most frequent complications in diabetes but there are no treatments beyond glucose control, due in part to the lack of an appropriate animal model to assess an effective therapy. This study was undertaken to characterize the degenerative and regenerative responses of peripheral nerves after induced sciatic nerve damage in transgenic rat insulin I promoter / human interferon beta (RIP/IFNbeta) mice made diabetic with a low dose of streptozotocin (STZ) as an animal model of diabetic complications. In vivo, histological and immunohistological studies of cutaneous and sciatic nerves were performed after left sciatic crush. Functional tests, cutaneous innervation, and sciatic nerve evaluation showed pronounced neurological reduction in all groups 2 weeks after crush. All animals showed a gradual recovery but this was markedly slower in diabetic animals in comparison with normoglycemic animals. The delay in regeneration in diabetic RIP/IFNbeta mice resulted in an increase in active Schwann cells and regenerating neurites 8 weeks after surgery. These findings indicate that diabetic-RIP/IFNbeta animals mimic human diabetic neuropathy. Moreover, when these animals are submitted to nerve crush they have substantial deficits in nerve regrowth, similar to that observed in diabetic patients. When wildtype animals were treated with the same dose of STZ, no differences were observed with respect to nontreated animals, indicating that low doses of STZ and the transgene are not implicated in development of the degenerative and regenerative events observed in our study. All these findings indicate that RIP/IFNbeta transgenic mice are a good model for diabetic neuropathy. PMID:19918773

  10. Metabolic neuropathies

    MedlinePlus

    Neuropathy - metabolic ... can be caused by many different things. Metabolic neuropathy may be caused by: A problem with the ... one of the most common causes of metabolic neuropathies. People who are at the highest risk for ...

  11. A novel Gypsy founder mutation, p.Arg1109X in the CMT4C gene, causes variable peripheral neuropathy phenotypes

    PubMed Central

    Gooding, R; Colomer, J; King, R; Angelicheva, D; Marns, L; Parman, Y; Chandler, D; Bertranpetit, J; Kalaydjieva, L

    2005-01-01

    Background: Linkage, haplotype and sequencing analysis in a large Spanish Gypsy kindred with multiple members affected by autosomal recessive peripheral neuropathy led to the identification of a novel mutation, p.Arg1109X, in the CMT4C gene. The screening of further unrelated patients, and of a panel of ethnically matched controls, showed that p.Arg1109X is an ancestral mutation which occurs in Gypsy populations across Europe and is the most common cause of autosomal recessive Charcot–Marie–Tooth disease in Spanish Gypsies. Objective: To report the identification of a novel Gypsy founder mutation causing autosomal recessive CMT4C disease in a sample of homozygous affected individuals. Results: The mutation was associated with a surprisingly broad spectrum of neuropathy phenotypes, with variation in the age at onset, rate of progression, severity of muscle and sensory involvement, the presence of scoliosis, and cranial nerve involvement. Conclusions: Ascertainment and further studies of CMT4C patients in this population will provide a unique opportunity for characterising the full range of clinical manifestations of the disease in a genetically homogeneous sample. PMID:16326826

  12. Effect of deoxycorticosterone acetate-salt-induced hypertension on diabetic peripheral neuropathy in alloxan-induced diabetic WBN/Kob rats.

    PubMed

    Ozaki, Kiyokazu; Hamano, Hiroko; Matsuura, Tetsuro; Narama, Isao

    2016-01-01

    The relationship between hypertension and diabetic peripheral neuropathy (DPN) has recently been reported in clinical research, but it remains unclear whether hypertension is a risk factor for DPN. To investigate the effects of hypertension on DPN, we analyzed morphological features of peripheral nerves in diabetic rats with hypertension. Male WBN/Kob rats were divided into 2 groups: alloxan-induced diabetic rats with deoxycorticosterone acetate-salt (DOCA-salt) treatment (ADN group) and nondiabetic rats with DOCA-salt treatment (DN group). Sciatic, tibial (motor) and sural (sensory) nerves were subjected to qualitative and quantitative histomorphological analysis. Systolic blood pressure in the two groups exhibited a higher value (>140 mmHg), but there was no significant difference between the two groups. Endoneurial blood vessels in both groups presented endothelial hypertrophy and narrowing of the vascular lumen. Electron microscopically, duplication of basal lamina surrounding the endothelium and pericyte of the endoneurial vessels was observed, and this lesion appeared to be more frequent and severe in the ADN group than the DN group. Many nerve fibers of the ADN and DN groups showed an almost normal appearance, whereas morphometrical analysis of the tibial nerve showed a significant shift to smaller fiber and myelin sizes in the ADN group compared with DN group. In sural nerve, the fiber and axon-size significantly shifted to a smaller size in ADN group compared with the DN group. These results suggest that combined diabetes and hypertension could induce mild peripheral nerve lesions with vascular changes. PMID:26989296

  13. Effect of deoxycorticosterone acetate-salt-induced hypertension on diabetic peripheral neuropathy in alloxan-induced diabetic WBN/Kob rats

    PubMed Central

    Ozaki, Kiyokazu; Hamano, Hiroko; Matsuura, Tetsuro; Narama, Isao

    2015-01-01

    The relationship between hypertension and diabetic peripheral neuropathy (DPN) has recently been reported in clinical research, but it remains unclear whether hypertension is a risk factor for DPN. To investigate the effects of hypertension on DPN, we analyzed morphological features of peripheral nerves in diabetic rats with hypertension. Male WBN/Kob rats were divided into 2 groups: alloxan-induced diabetic rats with deoxycorticosterone acetate-salt (DOCA-salt) treatment (ADN group) and nondiabetic rats with DOCA-salt treatment (DN group). Sciatic, tibial (motor) and sural (sensory) nerves were subjected to qualitative and quantitative histomorphological analysis. Systolic blood pressure in the two groups exhibited a higher value (>140 mmHg), but there was no significant difference between the two groups. Endoneurial blood vessels in both groups presented endothelial hypertrophy and narrowing of the vascular lumen. Electron microscopically, duplication of basal lamina surrounding the endothelium and pericyte of the endoneurial vessels was observed, and this lesion appeared to be more frequent and severe in the ADN group than the DN group. Many nerve fibers of the ADN and DN groups showed an almost normal appearance, whereas morphometrical analysis of the tibial nerve showed a significant shift to smaller fiber and myelin sizes in the ADN group compared with DN group. In sural nerve, the fiber and axon-size significantly shifted to a smaller size in ADN group compared with the DN group. These results suggest that combined diabetes and hypertension could induce mild peripheral nerve lesions with vascular changes. PMID:26989296

  14. Establishment of a Novel In Vitro Model for Predicting Incidence and Severity of Microtubule-targeting Agent-induced Peripheral Neuropathy.

    PubMed

    Sawaguchi, Yuichi; Ueno, Satoshi; Nishiyma, Yukiko; Yamazaki, Ryuta; Matsuzaki, Takeshi

    2015-12-01

    Peripheral neuropathy (PN) is a major dose-limiting side-effect of microtubule-targeting agents (MTAs), considered to be induced by inhibition of axonal microtubules. Therefore, it was thought that a useful method for predicting the frequencies of severe sensory-PN (FPN) would be to evaluate the neurite-disrupting effects of MTAs. Using neurite outgrowth from neuron-like cell lines, we comprehensively evaluated the neurite-disrupting effects of several anti-cancer drugs including MTAs, and the reversibility of the effects of MTAs. MTAs that induce PN showed neurite-disrupting effects more strongly than MTAs and anticancer drugs that do not induce PN, but the effects were not related to the FPN. On the other hand, MTAs with high FPN exhibited lower reversibility than those with low FPN. These findings suggest that neurite-disrupting effects are associated with the incidence of PN, and the reversibility of the effects is associated with FPN. PMID:26637853

  15. Enhanced Excitability of Primary Sensory Neurons and Altered Gene Expression of Neuronal Ion Channels in Dorsal Root Ganglion in Paclitaxel-Induced Peripheral Neuropathy

    PubMed Central

    Zhang, Haijun; Dougherty, Patrick M.

    2014-01-01

    Background 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. Methods Intrinsic membrane properties of dorsal root ganglion (DRG) neurons were studied by intracellular recordings. Multiple-gene real-time Polymerase Chain Reaction array was used to investigate gene expression of DRG neuronal ion channels. Results Paclitaxel increased the incidence of spontaneous activity from 4.8% to 27.1% in large 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, 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 neurons. After paclitaxel, 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 upregulation of HCN1 (fold change 1.76 ± 0.06) and Nav1.7 (1.26 ± 0.02) and downregulation of Kir channels (Kir1.1, 0.73 ± 0.05, Kir3.4, 0.66 ± 0.06) in paclitaxel-treated animals. Conclusions The increased neuronal excitability and the changes in gene expression of some neuronal ion channels in DRG may provide insight into the molecular and cellular basis of paclitaxel neuropathy, which may lead to novel therapeutic strategies. PMID:24534904

  16. Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db-/db- mouse, a type 2 diabetes model.

    PubMed

    Shi, Tie-Jun Sten; Zhang, Ming-Dong; Zeberg, Hugo; Nilsson, Johanna; Grünler, Jacob; Liu, Su-Xing; Xiang, Qiong; Persson, Jonas; Fried, Kaj J; Catrina, Sergiu Bogdan; Watanabe, Masahiko; Arhem, Peter; Brismar, Kerstin; Hökfelt, Tomas G M

    2013-01-01

    Diabetic peripheral neuropathy (DPN) is the most common complication in both type 1 and type 2 diabetes. Here we studied some phenotypic features of a well-established animal model of type 2 diabetes, the leptin receptor-deficient db(-)/db(-) mouse, and also the effect of long-term (6 mo) treatment with coenzyme Q10 (CoQ10), an endogenous antioxidant. Diabetic mice at 8 mo of age exhibited loss of sensation, hypoalgesia (an increase in mechanical threshold), and decreases in mechanical hyperalgesia, cold allodynia, and sciatic nerve conduction velocity. All these changes were virtually completely absent after the 6-mo, daily CoQ10 treatment in db(-)/db(-) mice when started at 7 wk of age. There was a 33% neuronal loss in the lumbar 5 dorsal root ganglia (DRGs) of the db(-)/db(-) mouse versus controls at 8 mo of age, which was significantly attenuated by CoQ10. There was no difference in neuron number in 5/6-wk-old mice between diabetic and control mice. We observed a strong down-regulation of phospholipase C (PLC) β3 in the DRGs of diabetic mice at 8 mo of age, a key molecule in pain signaling, and this effect was also blocked by the 6-mo CoQ10 treatment. Many of the phenotypic, neurochemical regulations encountered in lumbar DRGs in standard models of peripheral nerve injury were not observed in diabetic mice at 8 mo of age. These results suggest that reactive oxygen species and reduced PLCβ3 expression may contribute to the sensory deficits in the late-stage diabetic db(-)/db(-) mouse, and that early long-term administration of the antioxidant CoQ10 may represent a promising therapeutic strategy for type 2 diabetes neuropathy. PMID:23267110

  17. [Immune-mediated neuropathies].

    PubMed

    Stoll, G; Reiners, K

    2016-08-01

    The Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are the most common immune-mediated polyneuropathies, which can show variable clinical and electrophysiological manifestations. Rarer immune-mediated neuropathies encompass paraproteinemic neuropathies (PPN), multifocal motor neuropathy (MMN) and vasculitic neuropathies. The diagnosis usually relies on the history of symptom evolution, distribution of nerve dysfunction and particularly on characteristic features in nerve conduction studies, aided by cerebrospinal fluid (CSF) examination and nerve biopsy findings. The therapeutic toolbox encompasses corticosteroids, immunoglobulins and plasmapheresis often accompanied by long-term immunosuppression. It is important to note that immune-mediated neuropathies selectively respond to treatment and contraindications need to be considered. Despite treatment a considerable number of patients suffer from permanent neurological deficits. PMID:27474733

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

    PubMed Central

    Griffiths, Lisa A.; Flatters, Sarah J.L.

    2015-01-01

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

  19. 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

    PubMed Central

    Ishibashi, Fukashi; Taniguchi, Miki; Kojima, Rie; Kawasaki, Asami; Kosaka, Aiko; Uetake, Harumi

    2015-01-01

    Aims/Introduction 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. Materials and Methods 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. Results 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 < 0.05 to P < 0.001), and further increased relative to the severity of neuropathy (P < 0.0001). All morphological changes of both nerves were negatively associated with motor and sensory nerve conduction velocity (P = 0.01 to P < 0.0001), and directly associated with 2,000-Hz current perception threshold (P = 0.009 to P < 0.001). The significant corneal C fiber pathology occurred before developing the 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. Conclusions 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. PMID:25969719

  20. Peptide Mimetic of the S100A4 Protein Modulates Peripheral Nerve Regeneration and Attenuates the Progression of Neuropathy in Myelin Protein P0 Null Mice

    PubMed Central

    Moldovan, Mihai; Pinchenko, Volodymyr; Dmytriyeva, Oksana; Pankratova, Stanislava; Fugleholm, Kåre; Klingelhofer, Jorg; Bock, Elisabeth; Berezin, Vladimir; Krarup, Christian; Kiryushko, Darya

    2013-01-01

    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. PMID:23508572

  1. Peripheral Neuropathy in Adolescents and Young Adults With Type 1 and Type 2 Diabetes From the SEARCH for Diabetes in Youth Follow-up Cohort

    PubMed Central

    Jaiswal, Mamta; Lauer, Abigail; Martin, Catherine L.; Bell, Ronny A.; Divers, Jasmin; Dabelea, Dana; Pettitt, David J.; Saydah, Sharon; Pihoker, Catherine; Standiford, Debra A.; Rodriguez, Beatriz L.; Pop-Busui, Rodica; Feldman, Eva L.

    2013-01-01

    OBJECTIVE To estimate the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in a pilot study among youth participating in the SEARCH for Diabetes in Youth study. RESEARCH DESIGN AND METHODS DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI) (examination for foot abnormalities, distal vibration perception, and ankle reflexes). An MNSI exam (MNSIE) score >2 is diagnostic for DPN. RESULTS The MNSIE was completed in 399 subjects, including 329 youth with type 1 diabetes (mean age 15.7 ± 4.3 years, duration 6.2 ± 0.9 years) and 70 with type 2 diabetes (mean age 21.6 ± 4.1 years, duration 7.6 ± 1.8 years). Glycated hemoglobin (A1C) was similar in both groups (8.8 ± 1.8% for type 1 vs. 8.5 ± 2.9% for type 2). The prevalence of DPN was significantly higher in youth with type 2 compared with those with type 1 diabetes (25.7 vs. 8.2%; P < 0.0001). In unadjusted analyses, diabetes type, older age, longer duration of diabetes, increased waist circumference, elevated blood pressure, lower HDL cholesterol, and presence of microalbuminuria (urinary albumin-to-creatinine ratio >30 mg/g) were associated with DPN. The association between diabetes type and DPN remained significant after adjustment for age and sex (odds ratio 2.29 [95% CI 1.05–5.02], P = 0.03). CONCLUSIONS DPN prevalence among youth with type 2 diabetes approached rates reported in adult populations with diabetes. Our findings suggest not only that youth with diabetes are at risk for DPN but also that many already show measurable signs of DPN. PMID:24144652

  2. The expanding spectrum of PRPS1-associated phenotypes: three novel mutations segregating with X-linked hearing loss and mild peripheral neuropathy.

    PubMed

    Robusto, Michela; Fang, Mingyan; Asselta, Rosanna; Castorina, Pierangela; Previtali, Stefano C; Caccia, Sonia; Benzoni, Elena; De Cristofaro, Raimondo; Yu, Cong; Cesarani, Antonio; Liu, Xuanzhu; Li, Wangsheng; Primignani, Paola; Ambrosetti, Umberto; Xu, Xun; Duga, Stefano; Soldà, Giulia

    2015-06-01

    Next-generation sequencing is currently the technology of choice for gene/mutation discovery in genetically-heterogeneous disorders, such as inherited sensorineural hearing loss (HL). Whole-exome sequencing of a single Italian proband affected by non-syndromic HL identified a novel missense variant within the PRPS1 gene (NM_002764.3:c.337G>T (p.A113S)) segregating with post-lingual, bilateral, progressive deafness in the proband's family. Defects in this gene, encoding the phosphoribosyl pyrophosphate synthetase 1 (PRS-I) enzyme, determine either X-linked syndromic conditions associated with hearing impairment (eg, Arts syndrome and Charcot-Marie-Tooth neuropathy type X-5) or non-syndromic HL (DFNX1). A subsequent screening of the entire PRPS1 gene in 16 unrelated probands from X-linked deaf families led to the discovery of two additional missense variants (c.343A>G (p.M115V) and c.925G>T (p.V309F)) segregating with hearing impairment, and associated with mildly-symptomatic peripheral neuropathy. All three variants result in a marked reduction (>60%) of the PRS-I activity in the patients' erythrocytes, with c.343A>G (p.M115V) and c.925G>T (p.V309F) affecting more severely the enzyme function. Our data significantly expand the current spectrum of pathogenic variants in PRPS1, confirming that they are associated with a continuum disease spectrum, thus stressing the importance of functional studies and detailed clinical investigations for genotype-phenotype correlation. PMID:25182139

  3. Differential expression of neuregulin-1 isoforms and downregulation of erbin are associated with Erb B2 receptor activation in diabetic peripheral neuropathy

    PubMed Central

    2013-01-01

    Background Aberrant neuron/glia interactions can contribute to a variety of neurodegenerative diseases and we have previously demonstrated that enhanced activation of Erb B2, which is a member of the epidermal growth factor receptor (EGFR) family, can contribute to the development of diabetic peripheral neuropathy (DPN). In peripheral nerves, Erb B receptors are activated by various members of the neuregulin-1 (NRG1) family including NRG1 Type I, NRG1 Type II and NRG1 Type III to regulate Schwann cell (SC) growth, migration, differentiation and dedifferentiation. Alternatively, Erb B2 activity can be negatively regulated by association with the Erb B2-interacting protein, erbin. Since the effect of diabetes on the expression of NRG1 isoforms and erbin in peripheral nerve are unknown, the current study determined whether changes in NRG1 isoforms and erbin may be associated with altered Erb B2 signaling in DPN. Results Swiss Webster mice were rendered diabetic with streptozotocin (STZ) and after 12 weeks of diabetes, treated with erlotinib, an inhibitor of Erb B2 activation. Inhibition of Erb B2 signaling partially reversed several pathophysiologic aspects of DPN including a pronounced sensory hypoalgesia, nerve conduction velocity deficits and the decrease in epidermal nerve fiber innervation. We also observed a decrease of NRG1 Type III but an increase of NRG1 Type I level in diabetic sural nerves at early stage of diabetes. With disease progression, we detected reduced erbin expression and enhanced MAPK pathway activity in diabetic mice. Inhibition of Erb B2 receptor suppressed MAPK pathway activity in treated-diabetic sural nerves. Conclusions These results support that hyperglycemia may impair NRG1/Erb B2 signaling by disrupting the balance between NRG1 isoforms, decreasing the expression of erbin and correspondingly activating the MAPK pathway. Together, imbalanced NRG1 isoforms and downregulated erbin may contribute to the dysregulation of Erb B2 signaling in

  4. Vasculitic neuropathy following exposure to minocycline

    PubMed Central

    Baratta, John M.; Dyck, P. James B.; Brand, Patricio; Thaisetthawatkul, Pariwat; Dyck, Peter J.; Engelstad, JaNean K.; Goodman, Brent

    2015-01-01

    Objective: To report 3 patients with minocycline-induced autoimmunity resulting in peripheral nerve vasculitis. Methods: We report 3 patients who, during minocycline treatment for acne vulgaris, developed subacute onset of pain and weakness caused by vasculitis in single and multiple mononeuropathy patterns. Results: Each patient underwent either a nerve or muscle biopsy that confirmed vasculitis. One patient additionally developed systemic symptoms (including fever, fatigue, and night sweats) and another had a posterior circulation stroke. Symptoms developed with either early or prolonged use of minocycline. Despite withdrawal of minocycline, patients needed long-term immunotherapy to gain neurologic improvement. Conclusions: Our findings suggest that the typical neuropathy associated with minocycline use is painful single or multiple mononeuropathy due to peripheral nerve vasculitis, which may also be accompanied by presumed CNS vasculitis (presenting as stroke). PMID:26601119

  5. Peripheral Immune Cell Populations Associated with Cognitive Deficits and Negative Symptoms of Treatment-Resistant Schizophrenia

    PubMed Central

    Turner, Lorinda; Mustafa, Syed; Hatton, Alex; Smith, Kenneth G. C.; Lyons, Paul A.; Bullmore, Edward T.

    2016-01-01

    Background Hypothetically, psychotic disorders could be caused or conditioned by immunological mechanisms. If so, one might expect there to be peripheral immune system phenotypes that are measurable in blood cells as biomarkers of psychotic states. Methods We used multi-parameter flow cytometry of venous blood to quantify and determine the activation state of 73 immune cell subsets for 18 patients with chronic schizophrenia (17 treated with clozapine), and 18 healthy volunteers matched for age, sex, BMI and smoking. We used multivariate methods (partial least squares) to reduce dimensionality and define populations of differentially co-expressed cell counts in the cases compared to controls. Results Schizophrenia cases had increased relative numbers of NK cells, naïve B cells, CXCR5+ memory T cells and classical monocytes; and decreased numbers of dendritic cells (DC), HLA-DR+ regulatory T-cells (Tregs), and CD4+ memory T cells. Likewise, within the patient group, more severe negative and cognitive symptoms were associated with decreased relative numbers of dendritic cells, HLA-DR+ Tregs, and CD4+ memory T cells. Motivated by the importance of central nervous system dopamine signalling for psychosis, we measured dopamine receptor gene expression in separated CD4+ cells. Expression of the dopamine D3 (DRD3) receptor was significantly increased in clozapine-treated schizophrenia and covaried significantly with differentiated T cell classes in the CD4+ lineage. Conclusions Peripheral immune cell populations and dopaminergic signalling are disrupted in clozapine-treated schizophrenia. Immuno-phenotypes may provide peripherally accessible and mechanistically specific biomarkers of residual cognitive and negative symptoms in this treatment-resistant subgroup of patients. PMID:27244229

  6. Clinical and pathological features of an autosomal recessive neuropathy.

    PubMed

    Bouldin, T W; Riley, E; Hall, C D; Swift, M

    1980-06-01

    Two siblings are described, ages 49 and 45 years, having a distinct hereditary motor and sensory neuropathy (HMSN) with severe peroneal nerve involvement. The neuropathic symptoms began in childhood. Both patients have sensorineural deafness. The proband was found to have a cardiac conduction abnormality in the absence of known ischemic heart disease. Electrodiagnostic studies were consistent with a demyelinating peripheral neuropathy. The presence of parental consanguinity and absence of affected individuals in succeeding or preceding generations suggested that the sensorimotor neuropathy in this family is inherited in an autosomal recessive manner. The sural nerve of the proband had significant loss of myelinated fibers and demyelination but few regenerating myelinated fibers and no onion-bulbs. The pathological findings, while nonspecific, are not characteristic of the hypertrophic, neuronal or intermediate types of HMSN. PMID:6247456

  7. Comparison of clinical effectiveness of laser acupuncture and amitriptyline in diabetic peripheral neuropathy (DPN): a sham controlled randomized clinical trial

    NASA Astrophysics Data System (ADS)

    Hassan Khan, Imran; Anwar, Shahzad; Hanif, Asif; Ayub, Muhammad; Jamil Raja, Arsalan

    2014-02-01

    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

  8. Non-Systemic Vasculitic Neuropathy: An Enigmatic Clinical Entity

    PubMed Central

    Lubana, Sandeep Singh; Singh, Navdeep; Sanelli-Russo, Susan; Abrudescu, Adriana

    2015-01-01

    Patient: Female, 63 Final Diagnosis: Non-systemic vasculitic peripheral neuropathy Symptoms: Paresthesia Medication: — Clinical Procedure: Sural nerve biopsy Specialty: Rheumatology Objective: Challenging differential diagnosis Background: Non-systemic vasculitic peripheral neuropathy is a rare condition characterized by necrotizing inflammation resulting in luminal narrowing of the vasa nervorum, leading to ischemic injury to peripheral nerves. Here, we present the case of 63-year-old woman with subacute onset of severe hyperesthesia of the lower extremities accompanied by foot drop. Case Report: A 63-year-old woman with prolonged history of uncontrolled diabetes mellitus presented with subacute onset of severe bilateral lower extremity hyperesthesia and motor weakness along with left-sided foot drop. She had multiple emergency room visits with no relief of her symptoms. High doses of analgesics were insufficient to control pain. Laboratory tests were positive only for high erythrocyte sedimentation rate and C-reactive protein. A skin biopsy obtained 5 cm above the left lateral malleolus revealed medium-sized dermal vasculitis with dense mononuclear infiltrate. Electromyography showed peripheral neuropathy. A nerve biopsy was needed to reveal the exact diagnosis. Conclusions: Diagnosis of non-systemic vasculitic peripheral neuropathy can be delayed or missed in patients with uncontrolled diabetes mellitus, leading to significant morbidity. Elevated markers of inflammation in the absence of a possible explanation should prompt the clinician to perform a nerve biopsy; however, it is an invasive procedure and is associated with complications of post-neuropathic pain and delayed wound healing. Magnetic resonance angiography of the lower limbs, if combined with skin biopsy, can save the patient from undergoing nerve biopsy. PMID:26167722

  9. Can medical herbs stimulate regeneration or neuroprotection and treat neuropathic pain in chemotherapy-induced peripheral neuropathy?

    PubMed

    Schröder, Sven; Beckmann, Kathrin; Franconi, Giovanna; Meyer-Hamme, Gesa; Friedemann, Thomas; Greten, Henry Johannes; Rostock, Matthias; Efferth, Thomas

    2013-01-01

    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

  10. Can Medical Herbs Stimulate Regeneration or Neuroprotection and Treat Neuropathic Pain in Chemotherapy-Induced Peripheral Neuropathy?

    PubMed Central

    Schröder, Sven; Beckmann, Kathrin; Franconi, Giovanna; Greten, Henry Johannes; Rostock, Matthias; Efferth, Thomas

    2013-01-01

    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

  11. Alcoholic neuropathy

    MedlinePlus

    Neuropathy - alcoholic; Alcoholic polyneuropathy ... The exact cause of alcoholic neuropathy is unknown. It likely includes both a direct poisoning of the nerve by the alcohol and the effect of poor nutrition ...

  12. Neuropathy Tests

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Neuropathy Share this page: Was this page helpful? Overview | ... of testing are: To diagnose the presence of neuropathy and distinguish it from other conditions that may ...

  13. Prevalence of Neuropathy and Peripheral Arterial Disease and the Impact of Treatment in People With Screen-Detected Type 2 Diabetes

    PubMed Central

    Charles, Morten; Ejskjaer, Niels; Witte, Daniel R.; Borch-Johnsen, Knut; Lauritzen, Torsten; Sandbaek, Annelli

    2011-01-01

    OBJECTIVE There is limited evidence on how intensive multifactorial treatment (IT) improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. We examined the effects of early detection and IT of type 2 diabetes in primary care on the prevalence of diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) 6 years later in a pragmatic, cluster-randomized parallel group trial. RESEARCH DESIGN AND METHODS A stepwise screening program in 190 general practices in Denmark was used to identify 1,533 people with type 2 diabetes. General practices were randomized to deliver either IT or routine care (RC) as recommended through national guidelines. Participants were followed for 6 years and measures of DPN and PAD were applied. RESULTS We found no statistically significant effect of IT on the prevalence of DPN and PAD compared with RC. The prevalence of an ankle brachial index ≤0.9 was 9.1% (95% CI 6.0–12.2) in the RC arm and 7.3% (5.0–9.6) in the IT arm. In participants tested for vibration detection threshold and light touch sensation, the prevalence of a least one abnormal test was 34.8% (26.7–43.0) in the RC arm and 30.1% (24.1–36.1) in the IT arm. CONCLUSIONS In a population with screen-detected type 2 diabetes, we did not find that screening followed by IT led to a statistically significant difference in the prevalence of DPN and PAD 6 years after diagnosis. However, treatment levels were high in both groups. PMID:21816977

  14. Targeting of CaV3.2 T-type calcium channels in peripheral sensory neurons for the treatment of painful diabetic neuropathy.

    PubMed

    Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

    2014-04-01

    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. PMID:24482063

  15. Correspondence between neurophysiological and clinical measurements of chemotherapy-induced peripheral neuropathy: secondary analysis of data from the CI-PeriNoms study

    PubMed Central

    Griffith, Kathleen A.; Dorsey, Susan G.; Renn, Cynthia L.; Zhu, Shijun; Johantgen, Mary E.; Cornblath, David R.; Argyriou, Andreas A.; Cavaletti, Guido; Merkies, Ingemar S. J.; Alberti, Paola; Postma, Tjeerd J.; Rossi, Emanuela; Frigeni, Barbara; Bruna, Jordi; Velasco, Roser; Kalofonos, Haralabos P.; Psimaras, Dimitri; Ricard, Damien; Pace, Andrea; Galie, Edvina; Briani, Chiara; Torre, Chiara Dalla; Faber, Catharina G.; Lalisang, Roy I.; Boogerd, Willem; Brandsma, Dieta; Koeppen, Susanne; Hense, Joerg; Storey, Dawn J.; Kerrigan, Simon; Schenone, Angelo; Fabbri, Sabrina; Valsecchi, Maria Grazia

    2014-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) lacks standardized clinical measurement. The objective of the current secondary analysis was to examine data from the CIPN Outcomes Standardization (CI-PeriNomS) study for associations between clinical examinations and neurophysiological abnormalities. Logistic regression estimated the strength of associations of vibration, pin, and monofilament examinations with lower limb sensory and motor amplitudes. Examinations were classified as normal (0), moderately abnormal (1), or severely abnormal (2). Among 218 participants, those with class 1 upper extremity (UE) and class 1 or 2 lower extremity (LE) monofilament abnormality were 2.79 (95%CI: 1.28-6.07), 3.49 (95%CI: 1.61-7.55) and 4.42 (95%CI: 1.35-14.46) times more likely to have abnormal sural nerve amplitudes, respectively, compared to individuals with normal examinations. Likewise, those with class 2 UE and class 1 or 2 LE vibration abnormality were 8.65 (95%CI: 1.81-41.42), 2.54 (95%CI: 1.19-5.41) and 7.47 (95%CI: 2.49-22.40) times more likely to have abnormal sural nerve amplitudes, respectively, compared to participants with normal examinations. Abnormalities in vibration and monofilament examinations are associated with abnormal sural nerve amplitudes and are useful in identifying CIPN. PMID:24814100

  16. Correspondence between neurophysiological and clinical measurements of chemotherapy-induced peripheral neuropathy: secondary analysis of data from the CI-PeriNomS study.

    PubMed

    Griffith, Kathleen A; Dorsey, Susan G; Renn, Cynthia L; Zhu, Shijun; Johantgen, Mary E; Cornblath, David R; Argyriou, Andreas A; Cavaletti, Guido; Merkies, Ingemar S J; Alberti, Paola; Postma, Tjeerd J; Rossi, Emanuela; Frigeni, Barbara; Bruna, Jordi; Velasco, Roser; Kalofonos, Haralabos P; Psimaras, Dimitri; Ricard, Damien; Pace, Andrea; Galie, Edvina; Briani, Chiara; Dalla Torre, Chiara; Faber, Catharina G; Lalisang, Roy I; Boogerd, Willem; Brandsma, Dieta; Koeppen, Susanne; Hense, Joerg; Storey, Dawn J; Kerrigan, Simon; Schenone, Angelo; Fabbri, Sabrina; Valsecchi, Maria Grazia

    2014-06-01

    Chemotherapy-induced peripheral neuropathy (CIPN) lacks standardized clinical measurement. The objective of the current secondary analysis was to examine data from the CIPN Outcomes Standardization (CI-PeriNomS) study for associations between clinical examinations and neurophysiological abnormalities. Logistic regression estimated the strength of associations of vibration, pin, and monofilament examinations with lower limb sensory and motor amplitudes. Examinations were classified as normal (0), moderately abnormal (1), or severely abnormal (2). Among 218 participants, those with class 1 upper extremity (UE) and classes 1 or 2 lower extremity (LE) monofilament abnormality were 2.79 (95% confidence interval [CI]: 1.28-6.07), 3.49 (95%CI: 1.61-7.55), and 4.42 (95%CI: 1.35-14.46) times more likely to have abnormal sural nerve amplitudes, respectively, compared to individuals with normal examinations. Likewise, those with class 2 UE and classes 1 or 2 LE vibration abnormality were 8.65 (95%CI: 1.81-41.42), 2.54 (95%CI: 1.19-5.41), and 7.47 (95%CI: 2.49-22.40) times more likely to have abnormal sural nerve amplitudes, respectively, compared to participants with normal examinations. Abnormalities in vibration and monofilament examinations are associated with abnormal sural nerve amplitudes and are useful in identifying CIPN. PMID:24814100

  17. Bone Marrow-Derived Mesenchymal Stem Cells Improve Diabetic Neuropathy by Direct Modulation of Both Angiogenesis and Myelination in Peripheral Nerves

    PubMed Central

    Han, Ji Woong; Choi, Dabin; Lee, Min Young; Huh, Yang Hoon; Yoon, Young-sup

    2016-01-01

    Recent evidence has suggested that diabetic neuropathy (DN) is pathophysiologically related to both impaired angiogenesis and a deficiency of neurotrophic factors in the nerves. It is widely known that vascular and neural growths are intimately associated. Mesenchymal stem cells (MSCs) promote angiogenesis in ischemic diseases and have neuroprotective effects, particularly on Schwann cells. Accordingly, we investigated whether DN could be improved by local transplantation of MSCs by augmenting angiogenesis and neural regeneration such as remyelination. In sciatic nerves of streptozotocin (STZ)-induced diabetic rats, motor and sensory nerve conduction velocities (NCVs) and capillary density were reduced, and axonal atrophy and demyelination were observed. After injection of bone marrow-derived MSCs (BM-MSCs) into hindlimb muscles, NCVs were restored to near-normal levels. Histological examination demonstrated that injected MSCs were preferentially and durably engrafted in the sciatic nerves, and a portion of the engrafted MSCs were distinctively localized close to vasa nervora of sciatic nerves. Furthermore, vasa nervora increased in density, and the ultrastructure of myelinated fibers in nerves was observed to be restored. Real-time RT-PCR experiments showed that gene expression of multiple factors involved in angiogenesis, neural function, and myelination were increased in the MSC-injected nerves. These findings suggest that MSC transplantation improved DN through direct peripheral nerve angiogenesis, neurotrophic effects, and restoration of myelination. PMID:25975801

  18. Peripheral neuropathy in the twitcher mouse: accumulation of extracellular matrix in the endoneurium and aberrant expression of ion channels.

    PubMed

    Kagitani-Shimono, Kuriko; Mohri, Ikuko; Yagi, Takashi; Taniike, Masako; Suzuki, Kinuko

    2008-05-01

    Globoid cell leukodystrophy (GLD; Krabbe's disease), caused by a genetic galactosylceramidase deficiency, affects both the central and peripheral nervous systems (CNS and PNS). Allogenic hematopoietic stem-cell transplantation (HSCT) has been beneficial for clinical improvement of this disease. However, recent reports by Siddiqi et al. suggested that none of their transplanted patients achieved complete normalization of their peripheral nerve function, despite the well-documented remyelination of the CNS and PNS in the treated patients. We hypothesized that the PNS dysfunction in GLD is due to altered Schwann cell-axon interactions, resulting in structural abnormalities of the node of Ranvier and aberrant expression of ion channels caused by demyelination and that the persistence of this altered interaction is responsible for the dysfunction of the PNS after HSCT. Since there has not been any investigation of the Schwann cell-axonal relationship in twitcher mice, an authentic model of GLD, we first investigated structural abnormalities, focusing on the node of Ranvier in untreated twitcher mice, and compared the results with those obtained after receiving bone marrow transplantation (BMT). As expected, we found numerous supernumerary Schwann cells that formed structurally abnormal nodes of Ranvier. Similar findings, though at somewhat variable extent, were detected in mice treated with BMT. Activated supernumerary Schwann cells expressed GFAP immunoreactivity and generated Alcian blue-positive extracellular matrix (ECM) in the endoneurial space. The processes of these supernumerary Schwann cells often covered and obliterated the nodal regions. Furthermore, the distribution of Na(+) channel immunoreactivity was diffuse without the concentration at the nodes of Ranvier as seen in wild-type mice. Neither K(+) channels nor Neurexin IV/ Caspr/ Paranoidin (NCP-1) were detected in the twi/twi sciatic nerve. The results of our study suggest the importance of normalization

  19. Diabetic Neuropathy: Mechanisms to Management

    PubMed Central

    Edwards, James L.; Vincent, Andrea; Cheng, Thomas; Feldman, Eva L.

    2014-01-01

    Neuropathy is the most common and debilitating complication of diabetes and results in pain, decreased motility, and amputation. Diabetic neuropathy encompasses a variety of forms whose impact ranges from discomfort to death. Hyperglycemia induces oxidative stress in diabetic neurons and results in activation of multiple biochemical pathways. These activated pathways are a major source of damage and are potential therapeutic targets in diabetic neuropathy. Though therapies are available to alleviate the symptoms of diabetic neuropathy, few options are available to eliminate the root causes. The immense physical, psychological, and economic cost of diabetic neuropathy underscores the need for causally targeted therapies. This review covers the pathology, epidemiology, biochemical pathways, and prevention of diabetic neuropathy, as well as discusses current symptomatic and causal therapies and novel approaches to identify therapeutic targets. PMID:18616962

  20. Pattern Recognition Approach to Neuropathy and Neuronopathy

    PubMed Central

    Barohn, Richard J; Amato, Anthony A.

    2014-01-01

    Synopsis Neuropathic disorders encompass those that affect the neuron’s cell body or neuronopathies, those affecting the peripheral process, or peripheral neuropathies. The peripheral neuropathies can be broadly subdivided into the myelinopathies and axonopathies. These conditions can be hereditary or acquired. Each of these disorders has distinct clinical features that enable neurologists to recognize the various patterns of presentation. Once a particular pattern is established, further laboratory studies can be performed to confirm the clinical impression. PMID:23642713

  1. Nerve Ultrasound as a Decisive Tool in Nonsystemic Vasculitic Neuropathy: A Case Report

    PubMed Central

    Leupold, Daniela; Felbecker, Ansgar; Tettenborn, Barbara; Hundsberger, Thomas

    2016-01-01

    Introduction The additional value of peripheral nerve ultrasound in acquired immune-mediated neuropathies has recently been reported. Its impact in vasculitic neuropathy is yet to be defined. We report electrophysiological and nerve ultrasound studies in a patient with nonsystemic vasculitic neuropathy at first diagnosis and in response to immunosuppression. Case Report A 44-year-old female presented with painful neuropathy and weakness of the intrinsic hand muscles. Electrodiagnostic studies revealed severe axonal neuropathy of the nerves of the left arm. On nerve ultrasound, massive and patchy swelling of these nerves was detected. Clinical, laboratory, and radiological evidence of nonneuromuscular involvement and systemic vasculitic diseases was absent. Hence, nonsystemic vasculitic neuropathy was diagnosed without the possibility of histological verification. After 6 months of systemic immunosuppression with steroids and cyclophosphamide, clinical symptoms improved in parallel with neurosonography. In contrast, electrophysiological studies remained pathological despite clinical improvement. Conclusions Neurosonography studies in nonsystemic vasculitic neuropathy are rare but might be an ancillary technique to guide noninvasive diagnosis and therapeutic monitoring. Morphological analysis of nerves and changes in response to treatment could be well visualized. Additionally, neurosonography might be useful to target nerve biopsy. PMID:27403131

  2. Evaluation of DNA damage in Type 2 diabetes mellitus patients with and without peripheral neuropathy: A study in South Indian population

    PubMed Central

    Prasad, Mukul; Bronson, Stephen Charles; Warrier, Tushar; Badarinath, Agnihotram; Rai, Shivam; Baid, Kaushal; Sitaraman, Sneha; George, Alex; Moses, Anand; Saraswathy, Radha; Vasuki, Ranganathan; Shanmugam, Alagianambi

    2015-01-01

    Background: The increasing incidence of Type 2 diabetes mellitus globally has collaterally increased the incidence of diabetes-associated complications such as neuropathy. Oxidative stress induced DNA damage is one of the mechanisms implicated in the pathogenesis of diabetic complications. Here we aimed to evaluate the extent of DNA damage in diabetes patients with and without clinical neuropathy using the Cytokinesis Block Micronucleus Cytome assay, in a group of South Indian population. Materials and Methods: The Cytokinesis Block Micronucleus Cytome assay was performed in lymphocyte cultures of 42 type 2 diabetes patients (22 with neuropathy and 20 without neuropathy) and 42 age and sex matched controls. Nuclear aberrations like Nuclear Buds, Nucleoplasmic Bridges and Micronuclei were analyzed. Results: The frequency of nuclear aberrations in diabetes patients with neuropathy was higher than compared to diabetes patients without neuropathy. The mean frequencies of nuclear aberrations per cell in diabetes patients with neuropathy and without neuropathy were 0.02 ± 0.02 and 0.01 ± 0.01, respectively. This was significantly higher than in the controls (0.002 ± 0.002) (P < 0.0001). An increasing trend of nuclear aberrations in correlation with the duration of diabetes was observed. Conclusion: This study highlights the use of the Cytokinesis Block Micronucleus Cytome assay as a potent tool for the identification of DNA damage, which may prove to be useful biomarker to assess the severity diabetes-associated complications such as neuropathy. Implementation of this technique at the clinical level would potentially enhance the quality of management of patients with diabetes and its complications like neuropathy. PMID:25810640

  3. Peripheral neurologic abnormalities among roofing workers: sentinel case and clinical screening.

    PubMed

    Herbert, R; Gerr, F; Luo, J; Harris-Abbott, D; Landrigan, P J

    1995-01-01

    Peripheral neuropathy developed in a 52-y-old roofer who was exposed to multiple solvents in one-ply roofing systems. Forty roofers who were exposed to various roofing systems were assessed by symptoms, occupational history, standardized physical examination, and measurement of vibrotactile thresholds of the upper and lower extremities. After exclusion of roofers who were predisposed to peripheral neuropathy, we detected abnormal vibrotactile thresholds in 42% (p < .001) of roofers' dominant toes and in 36% (p < .001) of roofers' nondominant toes; fewer roofers had abnormal sensory physical examinations or reported neuritic symptoms. Roofing workers may be at increased risk of peripheral neuropathy, perhaps resulting from exposure to solvents--particularly n-hexane, associated with one-ply roofing systems. PMID:7574888

  4. Subcutaneous Bortezomib in Multiple Myeloma Patients Induces Similar Therapeutic Response Rates as Intravenous Application But It Does Not Reduce the Incidence of Peripheral Neuropathy

    PubMed Central

    Minarik, Jiri; Pavlicek, Petr; Pour, Ludek; Pika, Tomas; Maisnar, Vladimir; Spicka, Ivan; Jarkovsky, Jiri; Krejci, Marta; Bacovsky, Jaroslav; Radocha, Jakub; Straub, Jan; Kessler, Petr; Wrobel, Marek; Walterova, Lenka; Sykora, Michal; Obernauerova, Jarmila; Brozova, Lucie; Gregora, Evzen; Adamova, Dagmar; Gumulec, Jaromir; Adam, Zdenek; Scudla, Vlastimil; Hajek, Roman

    2015-01-01

    Objective 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. Patients and methods 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. Results 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%. Conclusions 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. PMID:25875484

  5. Association of the Charcot-Marie-Tooth disease gene ARHGEF10 with paclitaxel induced peripheral neuropathy in NCCTG N08CA (Alliance).

    PubMed

    Boora, Ganesh K; Kulkarni, Amit A; Kanwar, Rahul; Beyerlein, Peter; Qin, Rui; Banck, Michaela S; Ruddy, Kathryn J; Pleticha, Josef; Lynch, Cynthia A; Behrens, Robert J; Züchner, Stephan; Loprinzi, Charles L; Beutler, Andreas S

    2015-10-15

    The predisposition of patients to develop polyneuropathy in response to toxic exposure may have a genetic basis. The previous study Alliance N08C1 found an association of the Charcot-Marie-Tooth disease (CMT) gene ARHGEF10 with paclitaxel chemotherapy induced peripheral neuropathy (CIPN) related to the three non-synonymous, recurrent single nucleotide variants (SNV), whereby rs9657362 had the strongest effect, and rs2294039 and rs17683288 contributed only weakly. In the present report, Alliance N08CA was chosen to attempt to replicate the above finding. N08CA was chosen because it is the methodologically most similar study (to N08C1) performed in the CIPN field to date. N08CA enrolled patients receiving the neurotoxic chemotherapy agent paclitaxel. Polyneuropathy was assessed by serial repeat administration of the previously validated patient reported outcome instrument CIPN20. A study-wide, Rasch type model was used to perform extreme phenotyping in n=138 eligible patients from which "cases" and "controls" were selected for genetic analysis of SNV performed by TaqMan PCR. A significant association of ARHGEF10 with CIPN was found under the pre-specified primary endpoint, with a significance level of p=0.024. As in the original study, the strongest association of a single SNV was seen for rs9657362 (odds ratio=3.56, p=0.018). To further compare results across the new and the previous study, a statistical "classifier" was tested, which achieved a ROC area under the curve of 0.60 for N08CA and 0.66 for N08C1, demonstrating good agreement. Retesting of the primary endpoint of N08C1 in the replication study N08CA validated the association of ARHGEF10 with CIPN. PMID:26143528

  6. Case report: a balance training program using the Nintendo Wii Fit to reduce fall risk in an older adult with bilateral peripheral neuropathy.

    PubMed

    Hakim, Renée Marie; Salvo, Charles J; Balent, Anthony; Keyasko, Michael; McGlynn, Deidre

    2015-02-01

    A recent systematic review supported the use of strength and balance training for older adults at risk for falls, and provided preliminary evidence for those with peripheral neuropathy (PN). However, the role of gaming systems in fall risk reduction was not explored. The purpose of this case report was to describe the use of the Nintendo® Wii™ Fit gaming system to train standing balance in a community-dwelling older adult with PN and a history of recurrent near falls. A 76-year-old patient with bilateral PN participated in 1 h of Nintendo® Wii™ Fit balance training, two times a week for 6 weeks. Examination was conducted using a Computerized Dynamic Posturography system (i.e. Sensory Organization Test (SOT), Limits of Stability (LOS), Adaptation Test (ADT) and Motor Control Test (MCT) and clinical testing with the Berg Balance Scale (BBS), Timed Up and Go (TUG), Activities-specific Balance Confidence (ABC) scale and 30-s Chair Stand. Following training, sensory integration scores on the SOT were unchanged. Maximum excursion abilities improved by a range of 37-86% on the LOS test. MCT scores improved for amplitude with forward translations and ADT scores improved for downward platform rotations. Clinical scores improved on the BBS (28/56-34/56), ABC (57.5-70.6%) and TUG (14.9-10.9 s) which indicated reduced fall risk. Balance training with a gaming system showed promise as a feasible, objective and enjoyable method to improve physical performance and reduce fall risk in an individual with PN. PMID:25515202

  7. Risk assessment and predicting outcomes in patients with depressive symptoms: a review of potential role of peripheral blood based biomarkers.

    PubMed

    Jani, Bhautesh D; McLean, Gary; Nicholl, Barbara I; Barry, Sarah J E; Sattar, Naveed; Mair, Frances S; Cavanagh, Jonathan

    2015-01-01

    Depression is one of the major global health challenges and a leading contributor of health related disability and costs. Depression is a heterogeneous disorder and current methods for assessing its severity in clinical practice rely on symptom count, however this approach is unreliable and inconsistent. The clinical evaluation of depressive symptoms is particularly challenging in primary care, where the majority of patients with depression are managed, due to the presence of co-morbidities. Current methods for risk assessment of depression do not accurately predict treatment response or clinical outcomes. Several biological pathways have been implicated in the pathophysiology of depression; however, accurate and predictive biomarkers remain elusive. We conducted a systematic review of the published evidence supporting the use of peripheral biomarkers to predict outcomes in depression, using Medline and Embase. Peripheral biomarkers in depression were found to be statistically significant predictors of mental health outcomes such as treatment response, poor outcome and symptom remission; and physical health outcomes such as increased incidence of cardiovascular events and deaths, and all-cause mortality. However, the available evidence has multiple methodological limitations which must be overcome to make any real clinical progress. Despite extensive research on the relationship of depression with peripheral biomarkers, its translational application in practice remains uncertain. In future, peripheral biomarkers identified with novel techniques and combining multiple biomarkers may have a potential role in depression risk assessment but further research is needed in this area. PMID:25698954

  8. Correlation between Patient-Reported Symptoms and Ankle-Brachial Index after Revascularization for Peripheral Arterial Disease.

    PubMed

    Je, Hyung Gon; Kim, Bo Hyun; Cho, Kyoung Im; Jang, Jae Sik; Park, Yong Hyun; Spertus, John

    2015-01-01

    Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial index (ABI), and to evaluate possible correlation between the two methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before, and three months after peripheral revascularization. Mean PAQ summary scores improved significantly three months after revascularization (+49.3 ± 15 points, p < 0.001). PAQ scores relating to patient symptoms showed the largest improvement following revascularization. The smallest increases were seen in reported treatment satisfaction (all p's < 0.001). As expected the ABI of treated limbs showed significant improvement post-revascularization (p < 0.001). ABI after revascularization correlated with patient-reported changes in the physical function and QoL domains of the PAQ. Twenty-two percent of PAD patients were identified as having a poor response to revascularization (increase in ABI < 0.15). Interestingly, poor responders reported improvement in symptoms on the PAQ, although this was less marked than in patients with an increase in ABI > 0.15 following revascularization. In conclusion, data from the current study suggest a significant correlation between improvement in patient-reported outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing peripheral revascularization. PMID:25993299

  9. Correlation between Patient-Reported Symptoms and Ankle-Brachial Index after Revascularization for Peripheral Arterial Disease

    PubMed Central

    Je, Hyung Gon; Kim, Bo Hyun; Cho, Kyoung Im; Jang, Jae Sik; Park, Yong Hyun; Spertus, John

    2015-01-01

    Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial index (ABI), and to evaluate possible correlation between the two methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before, and three months after peripheral revascularization. Mean PAQ summary scores improved significantly three months after revascularization (+49.3 ± 15 points, p < 0.001). PAQ scores relating to patient symptoms showed the largest improvement following revascularization. The smallest increases were seen in reported treatment satisfaction (all p’s < 0.001). As expected the ABI of treated limbs showed significant improvement post-revascularization (p < 0.001). ABI after revascularization correlated with patient-reported changes in the physical function and QoL domains of the PAQ. Twenty-two percent of PAD patients were identified as having a poor response to revascularization (increase in ABI < 0.15). Interestingly, poor responders reported improvement in symptoms on the PAQ, although this was less marked than in patients with an increase in ABI > 0.15 following revascularization. In conclusion, data from the current study suggest a significant correlation between improvement in patient-reported outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing peripheral revascularization. PMID:25993299

  10. [A case of asymmetric demyelinating neuropathy in a patient with chronic graft-versus-host disease].

    PubMed

    Matsumoto, Hideyuki; Seki, Naoko; Yamamoto, Tomotaka; Oshima, Kumi; Asai, Takashi; Motokura, Toru; Ugawa, Yoshikazu; Goto, Jun; Tsuji, Shoji

    2005-10-01

    A 47-year-old man, who suffered from acute lymphocytic leukemia at 45 years old and was treated with hematopoietic stem cell transplantation at 46 years old after the induction of complete remission by the standard chemotherapy, developed the symptoms of chronic graft-versus-host disease (cGVHD) such as dry eyes, dry mouth, skin thickening, skin scaling, skin pigmentation and impaired liver function. He was admitted to our hospital because of the acute development of diplopia and weakness of his left upper extremity accompanying with the exacerbation of other symptoms of cGVHD. Neurological examinations revealed the right abducens nerve palsy and asymmetric muscular weakness of the extremities; the proximal part of the left upper extremity and the distal part of the right upper extremity were markedly involved. Neurophysiological studies including magnetic motor root stimulation revealed demyelinating neuropathy specifically involving the motor nerves. On the basis of these findings, a diagnosis of peripheral neuropathy associated with cGVHD was made. Nighteen reports are available on peripheral neuropathy in cGVHD patients, but to date little is known about the pathophysiology of this condition. Most of those patients have been diagnosed as having symmetric demyelinating polyneuropathy, such as Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy. In this study, contrary to previous reports, the asymmetric involvement of motor nerves is noteworthy. Accumulation and further analyses of the cases like the present case are necessary to elucidate the pathogenesis of peripheral neuropathy in cGVHD. PMID:16318371

  11. 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

    ClinicalTrials.gov

    2014-12-29

    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

  12. Diabetic Neuropathies

    PubMed Central

    Russell, James W.; Zilliox, Lindsay A.

    2014-01-01

    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

  13. Sensory neuropathy in two Border collie puppies.

    PubMed

    Vermeersch, K; Van Ham, L; Braund, K G; Bhatti, S; Tshamala, M; Chiers, K; Schrauwen, E

    2005-06-01

    A peripheral sensory neuropathy was diagnosed in two Border collie puppies. Neurological, electrophysiological and histopathological examinations suggested a purely sensory neuropathy with mainly distal involvement. Urinary incontinence was observed in one of the puppies and histological examination of the vagus nerve revealed degenerative changes. An inherited disorder was suspected. PMID:15971901

  14. Effect of niacin ER/lovastatin on claudication symptoms in patients with peripheral artery disease.

    PubMed

    Hiatt, William R; Hirsch, Alan T; Creager, Mark A; Rajagopalan, Sanjay; Mohler, Emile R; Ballantyne, Christie M; Regensteiner, Judith G; Treat-Jacobson, Diane; Dale, Rita A; Rooke, Thom

    2010-06-01

    In patients with peripheral artery disease (PAD), statins may improve the symptoms of claudication. The Intermittent Claudication Proof of Principle (ICPOP) study tested the hypothesis that the combination of extended release niacin plus lovastatin would improve exercise performance in patients with PAD and claudication compared with a diet intervention. A phase 3 double-blind, parallel-group, multi-center, 28-week multi-national study evaluated subjects with a history of claudication who had an ankle-brachial index (ABI) < or = 0.90, a reproducible peak treadmill walking time (PWT) of 1-20 minutes, and a low-density lipoprotein (LDL)-cholesterol level < 160 mg/dl (< 4.1 mmol/l). Subjects were randomly assigned to low-dose niacin 1000 mg plus lovastatin 40 mg (low niacin-statin), high-dose niacin 2000 mg plus lovastatin 40 mg (high niacin-statin), or diet intervention (diet). The co-primary efficacy endpoint of percent change in PWT and claudication onset time (COT) at 28 weeks was assessed using a graded treadmill protocol. At completion, 385 subjects were analyzed for safety and 370 subjects were analyzed for efficacy. The primary efficacy analysis showed no statistical significance for overall treatment effect at week 28 for the co-primary endpoint of PWT and COT. The PWT component of the primary endpoint increased 26.5% on diet, 37.8% on high niacin-statin (p = 0.137) and 38.6% on low niacin-statin (p = 0.096). Flushing as the most common event leading to discontinuation and treatment was associated with increases in liver enzymes, fasting blood glucose concentration and a decrease in platelet count. PMID:20212073

  15. Early diabetic neuropathy: Triggers and mechanisms

    PubMed Central

    Dobretsov, Maxim; Romanovsky, Dmitry; Stimers, Joseph R

    2007-01-01

    Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major reason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also clear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on clinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia. PMID:17226897

  16. Molecular network-based analysis of Guizhi-Shaoyao-Zhimu decoction, a TCM herbal formula, for treatment of diabetic peripheral neuropathy

    PubMed Central

    Zhao, Ning; Li, Jian; Li, Li; Niu, Xu-yan; Jiang, Miao; He, Xiao-juan; Bian, Zhao-xiang; Zhang, Ge; Lu, Ai-ping

    2015-01-01

    Aim: Guizhi-Shaoyao-Zhimu decoction (GSZ), a traditional Chinese medicine (TCM) herbal formula, has been shown effective in the treatment of diabetic peripheral neuropathy (DPN). In this study, network analysis was performed to decipher the molecular mechanisms of GSZ in the treatment of DPN. Methods: The chemical components of the 3 herbs forming GSZ, ie, Ramulus Cinnamomi (Guizhi), Paeonia lactiflora (Shaoyao) and Rhizoma Anemarrhenae (Zhimu), were searched in Chinese medicine dictionaries, and their target proteins were identified in PubChem. DPN genes were searched in PubMed gene databases. Ingenuity Pathway Analysis (IPA) was used to build the GSZ pharmacological network and DPN molecular network. The canonical pathways between the two networks were compared to decipher the molecular mechanisms of GSZ in the treatment of DPN. Results: Sixty-one protein targets for Guizhi, 31 targets for Shaoyao, 47 targets for Zhimu, as well as 23 genes related to DPN were identified and uploaded to IPA. The primary functions of the DPN molecular network were inflammatory response, metabolic disease, cellular assembly and organization. As far as the pharmacological network functions were concerned, Guizhi target proteins were involved in neurological disease, inflammatory disease, cellular growth and proliferation, cell signaling, molecular transport, and nucleic acid metabolism, Shaoyao target proteins were related to neurological disease, inflammatory disease, and Zhimu target proteins focused on cell death and survival, cellular movement, immune cell trafficking, DNA replication, recombination and repair, and cell cycle. In the three-herb combination GSZ, several new network functions were revealed, including the inflammatory response, gene expression, connective tissue development and function, endocrine system disorders, and metabolic disease. The canonical pathway comparison showed that Shaoyao focused on IL-12 signaling and production in macrophages, and Zhimu focused

  17. Impact of Genetic Reduction of NMNAT2 on Chemotherapy-Induced Losses in Cell Viability In Vitro and Peripheral Neuropathy In Vivo.

    PubMed

    Slivicki, Richard A; Ali, Yousuf O; Lu, Hui-Chen; Hohmann, Andrea G

    2016-01-01

    Nicotinamide mononucleotide adenylyl transferases (NMNATs) are essential neuronal maintenance factors postulated to preserve neuronal function and protect against axonal degeneration in various neurodegenerative disease states. We used in vitro and in vivo approaches to assess the impact of NMNAT2 reduction on cellular and physiological functions induced by treatment with a vinca alkaloid (vincristine) and a taxane-based (paclitaxel) chemotherapeutic agent. NMNAT2 null (NMNAT2-/-) mutant mice die at birth and cannot be used to probe functions of NMNAT2 in adult animals. Nonetheless, primary cortical cultures derived from NMNAT2-/- embryos showed reduced cell viability in response to either vincristine or paclitaxel treatment whereas those derived from NMNAT2 heterozygous (NMNAT2+/-) mice were preferentially sensitive to vincristine-induced degeneration. Adult NMNAT2+/- mice, which survive to adulthood, exhibited a 50% reduction of NMNAT2 protein levels in dorsal root ganglia relative to wildtype (WT) mice with no change in levels of other NMNAT isoforms (NMNAT1 or NMNAT3), NMNAT enzyme activity (i.e. NAD/NADH levels) or microtubule associated protein-2 (MAP2) or neurofilament protein levels. We therefore compared the impact of NMNAT2 knockdown on the development and maintenance of chemotherapy-induced peripheral neuropathy induced by vincristine and paclitaxel treatment using NMNAT2+/- and WT mice. NMNAT2+/- did not differ from WT mice in either the development or maintenance of either mechanical or cold allodynia induced by either vincristine or paclitaxel treatment. Intradermal injection of capsaicin, the pungent ingredient in hot chili peppers, produced equivalent hypersensitivity in NMNAT2+/- and WT mice receiving vehicle in lieu of paclitaxel. Capsaicin-evoked hypersensitivity was enhanced by prior paclitaxel treatment but did not differ in either NMNAT2+/- or WT mice. Thus, capsaicin failed to unmask differences in nociceptive behaviors in either paclitaxel

  18. Impact of Genetic Reduction of NMNAT2 on Chemotherapy-Induced Losses in Cell Viability In Vitro and Peripheral Neuropathy In Vivo

    PubMed Central

    Slivicki, Richard A.; Ali, Yousuf O.; Lu, Hui-Chen; Hohmann, Andrea G.

    2016-01-01

    Nicotinamide mononucleotide adenylyl transferases (NMNATs) are essential neuronal maintenance factors postulated to preserve neuronal function and protect against axonal degeneration in various neurodegenerative disease states. We used in vitro and in vivo approaches to assess the impact of NMNAT2 reduction on cellular and physiological functions induced by treatment with a vinca alkaloid (vincristine) and a taxane-based (paclitaxel) chemotherapeutic agent. NMNAT2 null (NMNAT2-/-) mutant mice die at birth and cannot be used to probe functions of NMNAT2 in adult animals. Nonetheless, primary cortical cultures derived from NMNAT2-/- embryos showed reduced cell viability in response to either vincristine or paclitaxel treatment whereas those derived from NMNAT2 heterozygous (NMNAT2+/-) mice were preferentially sensitive to vincristine-induced degeneration. Adult NMNAT2+/- mice, which survive to adulthood, exhibited a 50% reduction of NMNAT2 protein levels in dorsal root ganglia relative to wildtype (WT) mice with no change in levels of other NMNAT isoforms (NMNAT1 or NMNAT3), NMNAT enzyme activity (i.e. NAD/NADH levels) or microtubule associated protein-2 (MAP2) or neurofilament protein levels. We therefore compared the impact of NMNAT2 knockdown on the development and maintenance of chemotherapy-induced peripheral neuropathy induced by vincristine and paclitaxel treatment using NMNAT2+/- and WT mice. NMNAT2+/- did not differ from WT mice in either the development or maintenance of either mechanical or cold allodynia induced by either vincristine or paclitaxel treatment. Intradermal injection of capsaicin, the pungent ingredient in hot chili peppers, produced equivalent hypersensitivity in NMNAT2+/- and WT mice receiving vehicle in lieu of paclitaxel. Capsaicin-evoked hypersensitivity was enhanced by prior paclitaxel treatment but did not differ in either NMNAT2+/- or WT mice. Thus, capsaicin failed to unmask differences in nociceptive behaviors in either paclitaxel

  19. Paclitaxel-induced increase in NCX activity in subpopulations of nociceptive afferents: A protective mechanism against chemotherapy-induced peripheral neuropathy?

    PubMed

    Yilmaz, Eser; Gold, Michael S

    2016-07-01

    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

  20. Cardiovascular Risk Factors Increase the Risks of Diabetic Peripheral Neuropathy in Patients With Type 2 Diabetes Mellitus: The Taiwan Diabetes Study.

    PubMed

    Yang, Chun-Pai; Lin, Cheng-Chieh; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Hwang, Kai-Lin; Yang, Sing-Yu; Chen, Hsuan-Ju; Li, Tsai-Chung

    2015-10-01

    This study aimed to examine whether poor glycemic control, measured by glycated hemoglobin A1C (HbA1c) and other cardiovascular risk factors, can predict diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (DM).Patients aged ≥30 years with type 2 DM, enrolled in the National Diabetes Care Management Program, and free of DPN (n = 37,375) in the period 2002 to 2004 were included and followed up until 2011. The related factors were analyzed using Cox proportional hazards regression models.For an average follow-up of 7.00 years, 8379 cases of DPN were identified, with a crude incidence rate of 32.04/1000 person-years. After multivariate adjustment, patients with HbA1c levels 7 to 8%, 8 to 9%, 9 to 10%, and ≥10% exhibited higher risk of DPN (adjusted HR: 1.11 [1.04-1.20], 1.30 [1.21-1.40], 1.32 [1.22-1.43], and 1.62 [1.51-1.74], respectively) compared with patients with HbA1c level 6 to 7%. There was a significant linear trend in DPN incidence with increasing HbA1c (P < 0.001) and significant HRs of DPN for patients with HbA1c level ≥7%, blood pressure ≥130/85 mm Hg, triglycerides (TG) ≥150 mg/dL, high density of lipoprotein-cholesterol (HDL-C) <40 mg/dL in males and <50 mg/dL in females, low density of lipoprotein-cholesterol (LDL-C) ≥100 mg/dL, and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m.Patients with type 2 DM and HbA1c ≥7.0% exhibit increased risk of DPN, demonstrating a linear relationship. The incidence of DPN is also associated with poor glucose control and cardiovascular risk factors like hypertension, hyper-triglyceridemia, low HDL-C, high LDL-C, and decreased eGFR. PMID:26496307

  1. Autonomic neuropathies

    NASA Technical Reports Server (NTRS)

    Low, P. A.

    1998-01-01

    A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

  2. Mechanosensitivity during lower extremity neurodynamic testing is diminished in individuals with Type 2 Diabetes Mellitus and peripheral neuropathy: a cross sectional study

    PubMed Central

    2010-01-01

    Background Type 2 Diabetes Mellitus (T2DM) and diabetic symmetrical polyneuropathy (DSP) impact multiple modalities of sensation including light touch, temperature, position sense and vibration perception. No study to date has examined the mechanosensitivity of peripheral nerves during limb movement in this population. The objective was to determine the unique effects T2DM and DSP have on nerve mechanosensitivity in the lower extremity. Methods This cross-sectional study included 43 people with T2DM. Straight leg raise neurodynamic tests were performed with ankle plantar flexion (PF/SLR) and dorsiflexion (DF/SLR). Hip flexion range of motion (ROM), lower extremity muscle activity and symptom profile, intensity and location were measured at rest, first onset of symptoms (P1) and maximally tolerated symptoms (P2). Results The addition of ankle dorsiflexion during SLR testing reduced the hip flexion ROM by 4.3° ± 6.5° at P1 and by 5.4° ± 4.9° at P2. Individuals in the T2DM group with signs of severe DSP (n = 9) had no difference in hip flexion ROM between PF/SLR and DF/SLR at P1 (1.4° ± 4.2°; paired t-test p = 0.34) or P2 (0.9° ± 2.5°; paired t-test p = 0.31). Movement induced muscle activity was absent during SLR with the exception of the tibialis anterior during DF/SLR testing. Increases in symptom intensity during SLR testing were similar for both PF/SLR and DF/SLR. The addition of ankle dorsiflexion induced more frequent posterior leg symptoms when taken to P2. Conclusions Consistent with previous recommendations in the literature, P1 is an appropriate test end point for SLR neurodynamic testing in people with T2DM. However, our findings suggest that people with T2DM and severe DSP have limited responses to SLR neurodynamic testing, and thus may be at risk for harm from nerve overstretch and the information gathered will be of limited clinical value. PMID:20799983

  3. α4-Integrin Antibody Treatment Blocks Monocyte/Macrophage Traffic to, Vascular Cell Adhesion Molecule-1 Expression in, and Pathology of the Dorsal Root Ganglia in an SIV Macaque Model of HIV-Peripheral Neuropathy.

    PubMed

    Lakritz, Jessica R; Thibault, Derek M; Robinson, Jake A; Campbell, Jennifer H; Miller, Andrew D; Williams, Kenneth C; Burdo, Tricia H

    2016-07-01

    Traffic of activated monocytes into the dorsal root ganglia (DRG) is critical for pathology in HIV peripheral neuropathy. We have shown that accumulation of recently recruited (bromodeoxyuridine(+) MAC387(+)) monocytes is associated with severe DRG pathology and loss of intraepidermal nerve fibers in SIV-infected macaques. Herein, we blocked leukocyte traffic by treating animals with natalizumab, which binds to α4-integrins. SIV-infected CD8-depleted macaques treated with natalizumab either early (the day of infection) or late (28 days after infection) were compared with untreated SIV-infected animals sacrificed at similar times. Histopathology showed diminished DRG pathology with natalizumab treatment, including decreased inflammation, neuronophagia, and Nageotte nodules. Natalizumab treatment resulted in a decrease in the number of bromodeoxyuridine(+) (early), MAC387(+) (late), CD68(+) (early and late), and SIVp28(+) (late) macrophages in DRG tissues. The number of CD3(+) T lymphocytes in DRGs was not affected by natalizumab treatment. Vascular cell adhesion molecule 1, an adhesion molecule that mediates leukocyte traffic, was diminished in DRGs of all natalizumab-treated animals. These data show that blocking monocyte, but not T lymphocyte, traffic to the DRG results in decreased inflammation and pathology, supporting a role for monocyte traffic and activation in HIV peripheral neuropathy. PMID:27157989

  4. Alcoholic neuropathy

    MedlinePlus

    ... objects in the shoes Guarding the extremities to prevent injury from pressure Alcohol must be stopped to prevent the damage from ... The only way to prevent alcoholic neuropathy is not to drink excessive amounts of alcohol.

  5. Handcuff neuropathies.

    PubMed

    Stone, D A; Laureno, R

    1991-01-01

    Compressive neuropathy due to tight application of handcuffs occurred in 5 patients. The superficial radial nerve was affected in 8 hands and the median nerve in two. Neurologic deficits persisted as long as 3 years after handcuffing. Nerve conduction studies helped to exclude malingering and other diagnoses. All patients had been intoxicated when handcuffed or had been arrested with force. The handcuff mechanism, which allows accidental overtightening after application, is an unrecognized factor in these neuropathies. PMID:1985280

  6. Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-05-22

    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

  7. Central and peripheral SEP defects in neurologically symptomatic and asymptomatic subjects with low vitamin B12 levels.

    PubMed

    Jones, S J; Yu, Y L; Rudge, P; Kriss, A; Gilois, C; Hirani, N; Nijhawan, R; Norman, P; Will, R

    1987-12-01

    Somatosensory evoked potentials (SEPs) following median nerve stimulation were abnormal in 7 patients with sensory impairment due to vitamin B12 deficiency. Extensor plantar reflexes indicated a central sensory pathway lesion in 4 cases and absent tendon jerks suggested peripheral neuropathy in 4, but median nerve SEPs indicated a predominantly central lesion without marked peripheral nerve involvement in 6 and an axonal neuropathy without CNS involvement in 1. The latter had evidence of central slowing of conduction in SEPs following posterior tibial nerve stimulation. Consequently, it is suggested that the brunt of sensory pathway involvement usually falls on the CNS, although peripheral neuropathy may occur as the major abnormality in some cases. In 2 patients SEPs showed a marked improvement following treatment with vitamin B12 injections, one consistent with restored central conduction and the other with recovery from peripheral neuropathy. No peripheral or central SEP abnormalities were seen in 18 dairy-produce eating vegetarians with low vitamin B12 levels, although 6 reported mild sensory symptoms suggestive of peripheral neuropathy and 3 had corroborative clinical signs. PMID:2831310

  8. Progression in idiopathic, diabetic, paraproteinemic, alcoholic, and B12 deficiency neuropathy.

    PubMed

    Sachedina, Shafina; Toth, Cory

    2013-09-01

    We determined prospectively the clinical and electrophysiological progression of idiopathic, diabetic, paraproteinemic, alcoholic, and B12 deficiency neuropathy in 606 subjects over 3 years. We hypothesized that idiopathic peripheral neuropathy would demonstrate slower progression when compared with other etiologies. Laboratory assessments were used to determine the etiology of peripheral neuropathy at baseline and after 3 years. When compared with peripheral neuropathy related to type 1 or type 2 diabetes mellitus, subjects with idiopathic peripheral neuropathy progressed much slower, but demonstrated similar rates of progression to that of the other groups. Overall, detectable progression was minimal over 3 years. After 3 years, only 3% of cases of idiopathic peripheral neuropathy had any potentially identifiable causes discovered. Clinical and electrophysiological detection of very slow progression for these five types of peripheral neuropathy is possible using currently established clinical scales and standard electrophysiological techniques. PMID:24028193

  9. [Clinical diversity, diagnosis and treatment of hereditary amyloid neuropathy].

    PubMed

    Sekijima, Yoshiki

    2014-01-01

    Hereditary amyloid neuropathy includes hereditary ATTR, hereditary AGel, hereditary AApoAI, and hereditary Aβ2M amyloidosis. Among these diseases, hereditary ATTR is the most common type of amyloidosis caused by mutation in the transthyretin (TTR) gene. Hereditary ATTR amyloidosis is a life-threatening, multi-symptom, gain-of-toxic-function disease that may present with peripheral neuropathy, autonomic neuropathy, cardiomyopathy, ophthalmopathy, and/or leptomeningeal amyloidosis. In addition to the clinical symptoms described above, proven amyloid deposition in biopsy specimens and identification of disease-causing mutations in the TTR gene are necessary to establish the diagnosis. Deposition of amyloid in tissue can be demonstrated by Congo red staining of biopsy materials. Liver transplantation has been shown to be an effective therapeutic strategy for ameliorating hereditary ATTR amyloidosis, however, large numbers of patients are not suitable transplant candidates because of their age and/or advanced disease status. Recently, the clinical effects of TTR tetramer stabilizers, tafamidis and diflunisal, were demonstrated in randomised clinical trials, and tafamidis has been approved for the treatment of hereditary ATTR amyloidosis in European countries and in Japan. With the availability of disease-modifying therapies, early diagnosis and therapy become increasingly important in ATTR amyloidosis. PMID:25672679

  10. The Clinical Spectrum of Isolated Peripheral Motor Dysfunction

    PubMed Central

    Sanderson, Alan B.; Arnold, W. David; Elsheikh, Bakri; Kissel, John T.

    2015-01-01

    Introduction Isolated peripheral motor dysfunction due to lower motor neuron or peripheral nerve disorders presents an interesting challenge to clinicians because of the diverse differential diagnosis with a broad range of prognoses. Methods We retrospectively reviewed clinical data of adults who presented over 12 years with muscle weakness, atrophy, or fasciculations, but without hyperreflexia or sensory involvement. Results In 119 patients, 52% had a motor neuron disease (MND), 13% had immune neuropathies, 11% had genetic neuronopathies, 10% had residual or post-polio syndrome, 5% had benign fasciculation, 1% had an infectious etiology, and 8% were not given a final diagnosis. Only MND patients had cognitive dysfunction or frontal release signs. Bulbar and respiratory symptoms virtually excluded consideration of immune neuropathy. Conclusions Only half of the patients were diagnosed with MND. A significant minority have treatable conditions. Cognitive involvement, frontal release signs, and bulbar or respiratory symptoms are strongly suggestive of MND. PMID:25042002

  11. Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.

    PubMed

    Chance, Phillip F

    2006-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often

  12. Diabetic autonomic neuropathy.

    PubMed

    Clarke, B F; Ewing, D J; Campbell, I W

    1979-10-01

    This review attempts to outline the present understanding of diabetic autonomic neuropathy. The clinical features have been increasinly recognised but knowledge of the localization and morphology of the lesions and their pathogenesis remains fragmentary. A metabolic causation as postulated in somatic nerves accords best with clinical observations. Most bodily systems, particularly the cardiovascular, gastrointestinal and urogenital, are involved with added disturbances of thermoregulatory function and pupillary reflexes. Possible effects on neuroendocrine and peptidergic secretion and respiratory control await definition. Current interest centres around the development of a new generation of tests of autonomic nerve function that are simple, non-invasive, reproducible and allow precision in diagnosis and accurate quantitation. Most are based on cardiovascular reflexes and abnormality in them is assumed to reflect autonomic damage elsewhere. Probably no single test suffices and a battery of tests reflecting both parasympathetic and sympathetic function is preferable. Little is known of the natural history. The prevalence may be greater than previously suspected and although symptoms are mild in the majority, a few develop florid features. The relation of control and duration of diabetes to the onset and progression of autonomic neuropathy is not clearly established. Once tests of autonomic function become abnormal they usually remain abnormal. Symptomatic autonomic neuropathy carries a greatly increased mortality rate possibly due to indirect mechanisms such as renal failure and direct mechanisms such as cardio-resiratory arrest. Improved treatment of some of the more disabling symptoms has been possible in recent years. PMID:387501

  13. Effect of glycemic control on corneal nerves and peripheral neuropathy in streptozotocin-induced diabetic C57Bl/6J mice

    PubMed Central

    Yorek, Matthew S.; Obrosov, Alexander; Shevalye, Hanna; Lupachyk, Sergey; Harper, Matthew M.; Kardon, Randy H.; Yorek, Mark A.

    2016-01-01

    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 to 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 to untreated diabetic mice. However, good control of blood glucose was not totally sufficient in preventing diabetic neuropathy. PMID:25403729

  14. Animal Models of Autoimmune Neuropathy

    PubMed Central

    Soliven, Betty

    2014-01-01

    The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy have been provided by ex vivo immunologic studies, biopsy materials, electrophysiologic studies, and experimental models. This review article summarizes earlier seminal observations and highlights the recent progress in our understanding of immunopathogenesis of autoimmune neuropathies based on data from animal models. PMID:24615441

  15. Analyzing Relationship Between Monoclonal Gammopathy of Undetermined Significance (MGUS) with Different Types of Neuropathy: An Observational Study.

    PubMed

    Nabi, Shahzaib; Kahlon, Pushpinderdeep; Bozorgnia, Farshid; Arshad, Adeel; Saleem, Akmam; Kuriakose, Philip

    2016-06-01

    To analyze multiple variables, including immunoglobulin subtypes in patients with monoclonal gammopathy of undetermined significance (MGUS) and different types of neuropathy. This was a retrospective, single center study done in a tertiary care hospital in the United States. The data was collected for years 2001-2011. Inclusion criteria were the presence of MGUS and neuropathy. Exclusion criteria were the presence of other factors such as diabetes, vitamin B12 deficiency, alcoholism etc. which can cause neuropathy. Patients with IgM MGUS were compared with patients having Non-IgM MGUS. A total of 281 patients were analyzed in this study. The average age at the time of diagnosis of MGUS and neuropathy was 68 years. The most common type of neuropathy was sensorimotor peripheral neuropathy (46 %). The most common location of neuropathy was the lower extremities (68 %). Among our patients, 52 % had their neuropathy symptoms for 1-5 years before presenting to the clinic. When IgM MGUS was compared with Non-IgM MGUS, a statistically significant difference was found in terms of race (White vs. Others, OR 4.43, 95 % CI 2.13, 9.19, p < 0.001) and survival status (OR 1.98, 95 % CI 1.01, 3.90, p = 0.046). Patients with MGUS are prone to develop different types of neuropathies. Caucasians are more likely to have IgM MGUS as compared to other races. IgM MGUS is generally related to worse outcomes as compared to Non-IgM MGUS. Medical therapies, including gabapentin and pregabalin are effective treatments and the response rate can be as high as 80-90 % with these medications. PMID:27065581

  16. Auditory Neuropathy Spectrum Disorder Masquerading as Social Anxiety

    PubMed Central

    Rao, Mukund G.; Mishra, Shree; Varambally, Shivarama; Nagarajarao, Shivashankar; Gangadhar, Bangalore N.

    2015-01-01

    The authors report a case of a 47-year-old man who presented with treatment-resistant anxiety disorder. Behavioral observation raised clinical suspicion of auditory neuropathy spectrum disorder. The presence of auditory neuropathy spectrum disorder was confirmed on audiological investigations. The patient was experiencing extreme symptoms of anxiety, which initially masked the underlying diagnosis of auditory neuropathy spectrum disorder. Challenges in diagnosis and treatment of auditory neuropathy spectrum disorder are discussed. PMID:26351622

  17. Symptoms, disability and handicap in unilateral peripheral vestibular disorders. Effects of early presentation and initiation of balance exercises.

    PubMed

    Bamiou, D E; Davies, R A; McKee, M; Luxon, L M

    2000-01-01

    The aim of this study was to obtain a profile of disability and handicap in patients with unilateral peripheral vestibular disorders presenting to a specialist tertiary care unit. Two validated questionnaires were sent to patients who had a unilateral peripheral vestibular disorder as defined by strict criteria. Some patients still suffered moderate handicap and disability 5 years after the initial symptoms related to a unilateral vestibular disorder, although the duration of symptoms (onset to questionnaire completion) did not correlate with severity of disability and handicap, as judged by questionnaire scores. However, patients presenting to the unit within 6 months of onset of vertigo commenced balance exercises significantly earlier and had significantly lower disability scores than patients presenting later. A high proportion of non-compliance with, and delay in initiation of, vestibular rehabilitation exercises was noted in the total patient sample, while compliance with, and early initiation of, Cooksey Cawthorne exercises were significantly correlated with low disability and questionnaire scores. These findings suggest that early referral to a specialist balance unit for patients with persistent dizziness is associated with better outcome. PMID:11195943

  18. Painful neuropathy in a diabetic patient resulting from lung cancer and not diabetes: A case report

    PubMed Central

    YAO, HE-BIN; CHEN, YA-NING; SHANG, JIAN; HAN, QIAO-JUN

    2015-01-01

    The current study reports the case of a 61-year-old man with diabetes who was suffering from generalized pain over the whole body and gradually progressive numbness. The patient was initially diagnosed with diabetic peripheral neuropathy and received treatment, however, the symptoms persisted. In October 2010, the patient was admitted to the Chinese People's Liberation Army Navy General Hospital (Beijing, China) for the treatment of diabetes, however, a full-body sharp pain was also described, which was relieved upon massaging the area. Causes, other than diabetes, were investigated for these symptoms. Chest computed tomography and positron emission tomography-computed tomography scans revealed a mass shadow in the right lower lobe of the lung, with multiple lymphatic metastases. Lung cancer was diagnosed with a tumor-node-metastasis stage of T1N3Mx. Following treatment of the cancer with chemotherapy and radiotherapy, the patient's symptoms were significantly improved. The present study reports a rare case of a paraneoplastic neurological syndrome (PNS) that presented as painful neuropathy resulting from lung cancer, which mimicked diabetic peripheral neuropathy. PMID:26788221

  19. DIABETIC NEUROPATHY PART 2: PROXIMAL AND ASSYMMETRIC PHENOTYPES

    PubMed Central

    Pasnoor, Mamatha; Dimachkie, Mazen M.; Barohn, Richard J.

    2014-01-01

    Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is most common type of diabetic neuropathy, there are many other subtypes of diabetic neuropathies which have been defined since the 1800’s. Included in these descriptions are patients with proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most of these requires tight and stable glycemic control. Spontaneous recovery is seen in most of these conditions with diabetic control Immunotherapies have been tried in some of these conditions but are quite controversial. PMID:23642718

  20. Rationale, Science, and Economics of Surgical Nerve Decompression for Diabetic Neuropathy Foot Complications.

    PubMed

    Nickerson, David Scott

    2016-04-01

    Nerve decompression is effective and safe for dealing with the pain and numbness symptoms of the frequent nerve compression entrapments in diabetic symmetric peripheral neuropathy (DSPN). Evidence has accumulated of balance and stability improvements and protection against diabetic foot ulceration, recurrence and its complication cascade. Nerve decompression proffers significant benefit versus the large socioeconomic costs of DSPN complications. Advancing understanding of the mechanism of nerve compression and altered axonal activity in diabetes clarifies the basis of clinical benefit. Clinicians should seek out and recognize nerve entrapments and consider advising nerve decompression for relief of DSPN symptoms and prevention of complications. PMID:27013417

  1. Prediction of protective sensory loss, neuropathy and foot ulceration in type 2 diabetes

    PubMed Central

    Paisey, R B; Darby, T; George, A M; Waterson, M; Hewson, P; Paisey, C F; Thomson, M P

    2016-01-01

    Objectives To prospectively determine clinical and biochemical characteristics associated with the development of peripheral neuropathy, loss of protective sensation, and foot ulceration in persons with type 2 diabetes mellitus (DM) over 7 years. Research design and methods Graded monofilament (MF) testing, vibration perception threshold, and neuropathy symptom questionnaires were undertaken in 206 participants with type 2 DM without peripheral vascular disease or history of foot ulceration and 71 healthy participants without DM at baseline and after 7 years. 6 monthly glycosylated hemoglobin (HbA1c) levels and annual serum lipid profiles were measured during follow-up of those with DM. Incident foot ulceration was recorded at follow-up. Results Taller stature and higher quartiles of serum triglyceride and HbA1c levels were associated with neuropathy at follow-up (p=0.008). Remission of baseline neuropathy was observed in 7 participants at follow-up. 9 participants with type 2 DM developed foot ulcers by the end of the study, only 1 at low risk. Mean HbA1c levels were higher in those who developed foot ulceration (p<0.0001). 1 participant with neuropathy throughout developed a Charcot foot. Failure to perceive 2 or more 2, 4 and 6 g MF stimuli at baseline predicted loss of protective sensation at follow-up. Conclusions Tall stature and worse metabolic control were associated with progression to neuropathy. Mean HbA1c levels were higher in those who developed foot ulcers. Graded MF testing may enrich recruitment to clinical trials and assignation of high risk for foot ulceration. PMID:27239314

  2. Glutamate carboxypeptidase II inhibition behaviorally and physiologically improves pyridoxine-induced neuropathy in rats.

    PubMed

    Potter, Michelle C; Wozniak, Krystyna M; Callizot, Noelle; Slusher, Barbara S

    2014-01-01

    Pyridoxine is used as a supplement for treating conditions such as vitamin deficiency as well as neurological disorders such as depression, epilepsy and autism. A significant neurologic complication of pyridoxine therapy is peripheral neuropathy thought to be a result of long-term and high dose usage. Although pyridoxine-induced neuropathy is transient and can remit after its withdrawal, the process of complete recovery can be slow. Glutamate carboxypeptidase II (GCP II) inhibition has been shown to improve symptoms of both chemotherapy- and diabetic-induced neuropathy. This study evaluated if GCP II inhibition could behaviorally and physiologically improve pyridoxine-induced neuropathy. In the current study, high doses of pyridoxine (400 mg/kg, twice a day for seven days) were used to induce neuropathy in rats. An orally bioavailable GCP II inhibitor, 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA), was administered daily at a dose of 30 mg/kg starting from the onset of pyridoxine injections. Body weight, motor coordination, heat sensitivity, electromyographical (EMG) parameters and nerve morphological features were monitored. The results show beneficial effects of GCP II inhibition including normalization of hot plate reaction time, foot fault improvements and increased open field distance travelled. H wave frequency, amplitude and latency as well as sensory nerve conduction velocity (SNCV) were also significantly improved by 2-MPPA. Lastly, GCP II inhibition resulted in morphological protection in the spinal cord and sensory fibers in the lumbar region dorsal root ganglia (DRG). In conclusion, inhibition of GCP II may be beneficial against the peripheral sensory neuropathy caused by pyridoxine. PMID:25254647

  3. N-hexane neuropathy in offset printers.

    PubMed Central

    Chang, C M; Yu, C W; Fong, K Y; Leung, S Y; Tsin, T W; Yu, Y L; Cheung, T F; Chan, S Y

    1993-01-01

    In an offset printing factory with 56 workers, 20 (36%) developed symptomatic peripheral neuropathy due to exposure to n-hexane. Another 26 workers (46%) were found to have subclinical neuropathy. The initial change in the nerve conduction study was reduced amplitude of the sensory action potentials, followed by reduced amplitude of the motor action potentials, reduction in motor conduction velocities and increase in distal latencies. These changes indicate primary axonal degeneration with secondary demyelination. Sural nerve biopsy in a severe case showed giant axonal swellings due to accumulation of 10nm neurofilaments, myelin sheath attenuation and widening of nodal gaps. The development of neuropathy bore no direct relationship to the duration of exposure, hence factors such as individual susceptibility may be important. Optic neuropathy and CNS involvement were uncommon and autonomic neuropathy was not encountered. Images PMID:8505647

  4. Diabetic corneal neuropathy.

    PubMed Central

    Schultz, R O; Peters, M A; Sobocinski, K; Nassif, K; Schultz, K J

    1983-01-01

    Corneal epithelial lesions can be found in approximately one-half of asymptomatic patients with diabetes mellitus. These lesions are transient and clinically resemble the keratopathy seen in staphylococcal keratoconjunctivitis. Staphylococcal organisms, however, can be isolated in equal percentages from diabetic patients without keratopathy. Diabetic peripheral neuropathy was found to be related to the presence of diabetic keratopathy after adjusting for age with analysis of covariance. The strongest predictor of both keratopathy and corneal fluorescein staining was vibration perception threshold in the toes (P less than 0.01); and the severity of keratopathy was directly related to the degree of diminution of peripheral sensation. Other predictors of keratopathy were: reduced tear breakup time (P less than 0.03), type of diabetes (P less than 0.01), and metabolic status as indicated by c-peptide fasting (P less than 0.01). No significant relationships were found between the presence of keratopathy and tear glucose levels, endothelial cell densities, corneal thickness measurements, the presence of S epidermidis, or with duration of disease. It is our conclusion that asymptomatic epithelial lesions in the nontraumatized diabetic cornea can occur as a manifestation of generalized polyneuropathy and probably represent a specific form of corneal neuropathy. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:6676964

  5. Giant Axonal Neuropathy

    MedlinePlus

    ... Diversity Find People About NINDS NINDS Giant Axonal Neuropathy Information Page Table of Contents (click to jump ... done? Clinical Trials Organizations What is Giant Axonal Neuropathy? Giant axonal neuropathy (GAN) is a rare inherited ...

  6. Multifocal Motor Neuropathy

    MedlinePlus

    ... Diversity Find People About NINDS NINDS Multifocal Motor Neuropathy Information Page Table of Contents (click to jump ... done? Clinical Trials Organizations What is Multifocal Motor Neuropathy? Multifocal motor neuropathy is a progressive muscle disorder ...

  7. Additional Types of Neuropathy

    MedlinePlus

    ... A A Listen En Español Additional Types of Neuropathy Charcot's Joint Charcot's Joint, also called neuropathic arthropathy, ... can stop bone destruction and aid healing. Cranial Neuropathy Cranial neuropathy affects the 12 pairs of nerves ...

  8. Imaging of neuropathies about the hip.

    PubMed

    Martinoli, Carlo; Miguel-Perez, Maribel; Padua, Luca; Gandolfo, Nicola; Zicca, Anna; Tagliafico, Alberto

    2013-01-01

    Neuropathies about the hip may be cause of chronic pain and disability. In most cases, these conditions derive from mechanical or dynamic compression of a segment of a nerve within a narrow osteofibrous tunnel, an opening in a fibrous structure, or a passageway close to a ligament or a muscle. Although the evaluation of nerve disorders primarily relies on neurological examination and electrophysiology, diagnostic imaging is currently used as a complement to help define the site and aetiology of nerve compression and exclude other disease possibly underlying the patient' symptoms. Diagnosis of entrapment neuropathies about the hip with US and MR imaging requires an in-depth knowledge of the normal imaging anatomy and awareness of the anatomic and pathologic factors that may predispose or cause a nerve injury. Accordingly, the aim of this article is to provide a comprehensive review of hip neuropathies with an emphasis on the relevant anatomy, aetiology, clinical presentation, and their imaging appearance. The lateral femoral cutaneous neuropathy (meiralgia paresthetica), femoral neuropathy, sciatic neuropathy, obturator neuropathy, superior and inferior gluteal neuropathies and pudendal neuropathy will be discussed. PMID:21549536

  9. Cardiovascular autonomic neuropathy

    PubMed Central

    McCarty, Niamh

    2016-01-01

    Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this disease, including weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which occurred 2 years after his type 1 diabetes diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic hypotension, which suggests sympathetic denervation. He did not have complete cardiovascular autonomic reflex testing, which would have been helpful, but improved with aggressive diabetes treatment and the increase of beta-blockade. It is important to identify these patients to understand their signs and symptoms and consider appropriate therapies. PMID:27034552

  10. Cardiovascular autonomic neuropathy.

    PubMed

    McCarty, Niamh; Silverman, Barry

    2016-04-01

    Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this disease, including weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which occurred 2 years after his type 1 diabetes diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic hypotension, which suggests sympathetic denervation. He did not have complete cardiovascular autonomic reflex testing, which would have been helpful, but improved with aggressive diabetes treatment and the increase of beta-blockade. It is important to identify these patients to understand their signs and symptoms and consider appropriate therapies. PMID:27034552

  11. Giant axonal neuropathy: MRS findings.

    PubMed

    Alkan, Alpay; Kutlu, Ramazan; Sigirci, Ahmet; Baysal, Tamer; Altinok, Tayfun; Yakinci, Cengiz

    2003-10-01

    Giant axonal neuropathy (GAN) is a rare genetic disease of childhood involving the central and peripheral nervous systems. Axonal loss with several giant axons filled with neurofilaments is the main histopathological feature of peripheral nerve biopsies in this disease. Routine neuroimaging studies reveal diffuse hyperintensities in cerebral and cerebellar white matter. In this case report, the authors present the brain magnetic resonance spectroscopic features (normal N-acetylaspartate/creatine and increased choline/creatine and myoinositol/creatine ratios), which might indicate the absence of neuroaxonal loss and the presence of significant demyelination and glial proliferation in white matter, of an 11-year-old boy diagnosed with GAN. PMID:14569833

  12. CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy

    PubMed Central

    2012-01-01

    Background The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2) to bind to N-type voltage-activated calcium channels (CaV2.2) [Brittain et al. Nature Medicine 17:822–829 (2011)]. Results and discussion Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K) that bound with greater affinity to Ca2+ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBD3 peptide. This mutant peptide, conjugated to the cell penetrating motif of the HIV transduction domain protein TAT, exhibited greater anti-nociception in a rodent model of AIDS therapy-induced peripheral neuropathy when compared to the parent TAT-CBD3 peptide. Remarkably, intraperitoneal administration of TAT-CBD3A6K produced none of the minor side effects (i.e. tail kinking, body contortion) observed with the parent peptide. Interestingly, excitability of dissociated small diameter sensory neurons isolated from rats was also reduced by TAT-CBD3A6K peptide suggesting that suppression of excitability may be due to inhibition of T- and R-type Ca2+ channels. TAT-CBD3A6K had no effect on depolarization-evoked calcitonin gene related peptide (CGRP) release compared to vehicle control. Conclusions Collectively, these results establish TAT-CBD3A6K as a peptide therapeutic with greater efficacy in an AIDS therapy-induced model of peripheral neuropathy than its parent peptide, TAT-CBD3. Structural modifications of the CBD3 scaffold peptide may result in peptides with selectivity against a particular subset of voltage-gated calcium channels resulting in a multipharmacology of action on the target. PMID

  13. MNGIE neuropathy: five cases mimicking chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Bedlack, Richard S; Vu, Tuan; Hammans, Simon; Sparr, Steven A; Myers, Bennett; Morgenlander, Joel; Hirano, Michio

    2004-03-01

    We report five patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) who had demyelinating peripheral neuropathy. The MNGIE neuropathy had clinical and electrodiagnostic features typical of acquired, rather than inherited, etiologies. In fact, three patients were actually treated for chronic inflammatory demyelinating polyneuropathy (CIDP). We discuss findings that may help distinguish patients with MNGIE from those with CIDP. PMID:14981734

  14. Lithium-Induced Motor Neuropathy: An Unusual Presentation

    PubMed Central

    Mohapatra, Satyakam; Sahoo, Manas Ranjan; Rath, Neelmadhav

    2016-01-01

    Peripheral neuropathy secondary to lithium is under-recognized. Most cases of polyneuropathy were reported with lithium intoxication. However, very few cases were reported without lithium toxicity. We present a case of motor neuropathy due to the use of lithium in a 26-year-old male with a therapeutic lithium level. PMID:27335523

  15. Management of Diabetic Neuropathy

    PubMed Central

    Ali, Raymond Azman

    2003-01-01

    Diabetes mellitus is the commonest cause of neuropathy worldwide. Diabetic neuropathy (DN) develops in about 4–10% of diabetic patients after 5 years and in 15% after 20 years. Four main mechanisms have been postulated to underlie the pathogenesis of DN. Diabetic neuropathy can be divided into symmetrical and asymmetrical neuropathies. Diabetic Autonomic Neuropathy (DAN) parallels the severity of DSN, and affects primarily the cardiovascular, gastrointestinal, genitourinary and integumentary systems. The cornerstone of treatment of diabetic neuropathy is optimization of glycaemic control. Future treatments for diabetic neuropathy should address the underlying pathogenesis. PMID:23386794

  16. Metabolic neuropathies

    MedlinePlus

    ... Neurology and General Medicine . 5th ed. Philadelphia, PA: Elsevier; 2014:chap 15. Patterson MC, Percy AK. Peripheral ... Infancy, Childhood, and Adolescence . 2nd ed. Philadelphia, PA: Elsevier; 2015:chap 19. Ralph JW, Aminoff MJ. Neuromuscular ...

  17. Deletion of KCC3 in parvalbumin neurons leads to locomotor deficit in a conditional mouse model of peripheral neuropathy associated with agenesis of the corpus callosum.

    PubMed

    Ding, Jinlong; Delpire, Eric

    2014-11-01

    Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC or ACCPN) is an autosomal recessive disease caused by the disruption of the SLC12A6 gene, which encodes the K-Cl cotransporter-3 (KCC3). A ubiquitous deletion of KCC3 in mice leads to severe locomotor deficits similar to ACCPN patients. However, the underlying pathological mechanism leading to the disease remains unclear. Even though a recent study suggests that the neuropathic features of ACCPN are mostly due to neuronal loss of KCC3, the specific cell type responsible for the disease is still unknown. Here we established four tissue specific KCC3 knockout mouse lines to explore the cell population origin of ACCPN. Our results showed that the loss of KCC3 in parvalbumin-positive neurons led to significant locomotor deficit, suggesting a crucial role of these neurons in the development of the locomotor deficit. Interestingly, mice in which KCC3 deletion was driven by the neuron-specific enolase (NSE) did not develop any phenotype. Furthermore, we demonstrated that nociceptive neurons targeted with Nav1.8-driven CRE and Schwann cells targeted with a desert hedgehog-driven CRE were not involved in the development of ACCPN. Together, these results establish that the parvalbumin-positive neuronal population is an important player in the pathogenic development of ACCPN. PMID:25116249

  18. Repeated monitoring of corneal nerves by confocal microscopy as an index of peripheral neuropathy in type-1 diabetic rodents and the effects of topical insulin

    PubMed Central

    Chen, Debbie K.; Frizzi, Katie E.; Guernsey, Lucie S.; Ladt, Kelsey; Mizisin, Andrew P.; Calcutt, Nigel A.

    2013-01-01

    We developed a reliable imaging and quantitative analysis method for in vivo corneal confocal microscopy in rodents and used it to determine whether models of type-1 diabetes replicate the depletion of corneal nerves reported in diabetic patients. Quantification was reproducible between observers and stable across repeated time points in two rat strains. Longitudinal studies were performed in normal and streptozotocin-diabetic rats, with innervation of plantar paw skin quantified using standard histological methods after 40 weeks of diabetes. Diabetic rats showed an initial increase, then a gradual reduction in occupancy of nerves in the sub-basal plexus so that values were significantly lower at week 40 (68±6%) than age-matched controls (80±2%). No significant loss of stromal or intra-epidermal nerves was detected. In a separate study, insulin was applied daily to the eye of control and streptozotocin-diabetic mice and this treatment prevented depletion of nerves of the sub-basal plexus. Longitudinal studies are viable in rodents using corneal confocal microscopy and depletion of distal corneal nerves precedes detectable loss of epidermal nerves in the foot, suggesting that diabetic neuropathy is not length dependent. Loss of insulin-derived neurotrophic support may contribute to the pathogenesis of corneal nerve depletion in type 1 diabetes. PMID:24147903

  19. Autonomic neuropathy

    MedlinePlus

    ... blood pressure, heart rate, sweating, bowel and bladder emptying, and digestion. ... Difficulty beginning to urinate Feeling of incomplete bladder emptying Leaking urine Other symptoms may include: Sweating too ...

  20. Giant axonal neuropathy: visual and oculomotor deficits.

    PubMed

    Kirkham, T H; Guitton, D; Coupland, S G

    1980-08-01

    Giant axonal neuropathy, a generalised disorder or neurofilaments, presents as a chronic, progressive peripheral neuropathy in childhood. Evidence for central nervous system involvement is demonstrated in this study of four male patients with giant axonal neuropathy who had defective visual function and abnormal ocular motility. The visual system was studied by electroretinography, which showed normal retinal function, and by visual evoked potentials, which showed disease of both optic nerves and retrochiasmal visual pathways. The ocular motility disorder, studied by electrooculography, comprised defective pursuit, inability to maintain eccentric gaze with gaze paretic and rebound nystagmus, abnormal optokinetic responses and failure of suppression of the vestibulo-ocular reflex by fixation. These findings suggested involvement by giant axonal neuropathy of the cerebellar and brain stem pathways important in the control of ocular motility. PMID:7192592

  1. Bicycling induced pudendal nerve pressure neuropathy.

    PubMed

    Silbert, P L; Dunne, J W; Edis, R H; Stewart-Wynne, E G

    1991-01-01

    Pudendal neuropathies are well recognised as part of more generalised peripheral neuropathies; however, focal abnormalities of the pudendal nerve due to cycling-related injuries have been infrequently reported. We describe two patients who developed pudendal neuropathies secondary to pressure effects on the perineum from racing-bicycle saddles. Both were male competitive athletes, one of whom developed recurrent numbness of the penis and scrotum after prolonged cycling; the other developed numbness of the penis, an altered sensation of ejaculation, with disturbance of micturition and reduced awareness of defecation. Both patients improved with alterations in saddle position and riding techniques. We conclude that pudendal nerve pressure neuropathy can result from prolonged cycling, particularly when using a poor riding technique. PMID:1821826

  2. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society.

    PubMed

    2010-06-01

    Revision of the guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy, published in 2005, has become appropriate due to publication of more relevant papers. Most of the new studies focused on small fiber neuropathy (SFN), a subtype of neuropathy for which the diagnosis was first developed through skin biopsy examination. This revision focuses on the use of this technique to diagnose SFN. Task force members searched the Medline database from 2005, the year of the publication of the first EFNS guideline, to June 30(th), 2009. All pertinent papers were rated according to the EFNS and PNS guidance. After a consensus meeting, the task force members created a manuscript that was subsequently revised by two experts (JML and JVS) in the field of peripheral neuropathy and clinical neurophysiology, who were not previously involved in the use of skin biopsy. Distal leg skin biopsy with quantification of the linear density of intraepidermal nerve fibers (IENF), using generally agreed upon counting rules, is a reliable and efficient technique to assess the diagnosis of SFN (level A recommendation). Normative reference values are available for bright-field immunohistochemistry (level A recommendation) but not yet for confocal immunofluorescence or the blister technique. The morphometric analysis of IENF density, either performed with bright-field or immunofluorescence microscopy, should always refer to normative values matched for age (level A recommendation). Newly established laboratories should undergo adequate training in a well established skin biopsy laboratory and provide their own stratified age and gender-matched normative values, intra- and interobserver reliability, and interlaboratory agreement. Quality control of the procedure at all levels is mandatory (Good Practice Point). Procedures to quantify subepidermal nerve fibers and autonomic innervated structures, including erector pili muscles, and skin vessels are under development but need to

  3. [Not only optic neuropathy: new molecular and clinical aspects of OPA1 gene mutations].

    PubMed

    Ołdak, Monika; Sciezyńska, Aneta; Szulborski, Kamil; Szaflik, Jacek P; Szaflik, Jerzy

    2014-01-01

    Autosomal dominant optic nerve atrophy is the most frequent dominantly inherited optic neuropathy. The main causesof the disease are OPA1 gene mutations, which are detected in about 60% of patients. Encoded by the nuclear genome the OPA1 protein plays an important role in a wide variety of processes crucial to the proper functioning of mitochondria, the role of OPAl in many of them has been discovered recently. A detailed study of patients with mutations in the OPA1 gene has shown that about 20% of them present symptoms of a multiple system disease, which may include hearing loss, progressive external ophthalmoplegia, ataxia, myopathy, peripheral neuropathy, spastic paraparesis and multiple sclerosis-like illness. This clinical manifestation is difficult to differentiate from other neurodegenerative diseases, that is why genetic testing is very important in order to determine the molecular basis of the disease in these patients. PMID:25137924

  4. Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation.

    PubMed

    Komirishetty, Prashanth; Areti, Aparna; Sistla, Ramakrishna; Kumar, Ashutosh

    2016-08-01

    Neuropathic pain is initiated or caused due to the primary lesion or dysfunction in the nervous system and is proposed to be linked to a cascade of events including excitotoxicity, oxidative stress, neuroinflammation and apoptosis. Oxidative/nitrosative stress aggravates the neuroinflammation and neurodegeneration through poly (ADP) ribose polymerase (PARP) overactivation. Hence, the present study investigated the antioxidant and anti-inflammatory effects of the phytoconstituent; morin in chronic constriction injury (CCI) induced neuropathy. Neuropathic pain was induced by chronic constriction of the left sciatic nerve in rats, and the effect of morin (15 and 30 mg/kg, p.o.) was evaluated by measuring behavioural and biochemical changes. Mechanical, chemical and thermal stimuli confirmed the CCI-induced neuropathic pain and treatment with morin significantly improved these behavioural deficits and improved the sciatic functional index by the 14th day after CCI induction. After 14 days of CCI induction, oxidative/nitrosative stress and inflammatory markers were elevated in rat lumbar spinal cord. Oxidative stress induced PARP overactivation resulted in depleted levels of ATP and elevated levels of poly (ADP) ribose (PAR). Treatment with morin reduced the levels of nitrites, restored glutathione levels and abrogated the oxidant induced DNA damage. It also mitigated the increased levels of TNF-α and IL-6. Protein expression studies confirmed the PARP inhibition and anti-inflammatory activity of morin. Findings of this study suggest that morin, by virtue of its antioxidant properties, limited PARP overactivation and neuroinflammation and protected against CCI induced functional, behavioural and biochemical deficits. PMID:27084773

  5. Severe Acute Axonal Neuropathy following Treatment with Arsenic Trioxide for Acute Promyelocytic Leukemia: a Case Report

    PubMed Central

    Kühn, Marcus; Sammartin, Kety; Nabergoj, Mitja; Vianello, Fabrizio

    2016-01-01

    Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide. PMID:27158436

  6. Tetrahydrocurcumin exerts protective effect on vincristine induced neuropathy: Behavioral, biochemical, neurophysiological and histological evidence.

    PubMed

    Greeshma, N; Prasanth, K G; Balaji, Bhaskar

    2015-08-01

    Hyperalgesia, allodynia, delayed motor nerve conduction velocity, oxidative stress and axonal damage are signs and symptoms of chemotherapy induced peripheral neuropathy (CIPN). Present treatment/preventive strategies of CIPN are futile and the neuropathy may even lead to discontinuation of chemotherapy. In this study, we evaluated the protective effect of tetrahydrocurcumin (THC) 40 and 80mg/kg in experimental vincristine induced neuropathy in rats. Hyperalgesia was assessed by hot plate (thermal), Randall-Selitto (mechanical) test, allodynia was assessed by cold plate (thermal) test, functional loss was measured by sciatic function index, nociception was evaluated by formalin test. Neurophysiological recordings were carried out to assess motor nerve conduction velocity. Total calcium levels, oxidative stress and TNF-α was measured in sciatic nerve tissue homogenate to assess neuropathy. Histopathological changes was observed on sciatic nerve to assess the protective effect of THC against the vincristine. Pregabalin was used as a standard in this study. Rats administered with THC at 80mg/kg significantly attenuated the vincristine induced neuropathic pain manifestations which may be due to its multiple actions including anti-nociceptive, anti-inflammatory, neuroprotective, calcium inhibitory and antioxidant effect. This study delineates that THC can be a promising candidate for the prevention of CIPN by chemotherapeutic agents. PMID:26102012

  7. Immunotherapy Prospects for Painful Small-fiber Sensory Neuropathies and Ganglionopathies.

    PubMed

    Oaklander, Anne Louise

    2016-01-01

    The best-known peripheral neuropathies are those affecting the large, myelinated motor and sensory fibers. These have well-established immunological causes and therapies. Far less is known about the somatic and autonomic "small fibers"; the unmyelinated C-fibers, thinly myelinated A-deltas, and postganglionic sympathetics. The small fibers sense pain and itch, innervate internal organs and tissues, and modulate the inflammatory and immune responses. Symptoms of small-fiber neuropathy include chronic pain and itch, sensory impairment, edema, and skin color, temperature, and sweating changes. Small-fiber polyneuropathy (SFPN) also causes cardiovascular, gastrointestinal, and urological symptoms, the neurologic origin of which often remains unrecognized. Routine electrodiagnostic study does not detect SFPN, so skin biopsies immunolabeled to reveal axons are recommended for diagnostic confirmation. Preliminary evidence suggests that dysimmunity causes some cases of small-fiber neuropathy. Several autoimmune diseases, including Sjögren and celiac, are associated with painful small-fiber ganglionopathy and distal axonopathy, and some patients with "idiopathic" SFPN have evidence of organ-specific dysimmunity, including serological markers. Dysimmune SFPN first came into focus in children and teenagers as they lack other risk factors, for example diabetes or toxic exposures. In them, the rudimentary evidence suggests humoral rather than cellular mechanisms and complement consumption. Preliminary evidence supports efficacy of corticosteroids and immunoglobulins in carefully selected children and adult patients. This paper reviews the evidence of immune causality and the limited data regarding immunotherapy for small-fiber-predominant ganglionitis, regional neuropathy (complex regional pain syndrome), and distal SFPN. These demonstrate the need to develop case definitions and outcome metrics to improve diagnosis, enable prospective trials, and dissect the mechanisms of

  8. Degenerative myelopathy associated with a missense mutation in the superoxide dismutase 1 (SOD1) gene progresses to peripheral neuropathy in Pembroke Welsh corgis and boxers.

    PubMed

    Shelton, G Diane; Johnson, Gayle C; O'Brien, Dennis P; Katz, Martin L; Pesayco, Jill P; Chang, Brian J; Mizisin, Andrew P; Coates, Joan R

    2012-07-15

    Canine degenerative myelopathy (DM) is an adult-onset, fatal neurodegenerative disease with many similarities to an upper-motor-neuron-onset form of human amyotrophic lateral sclerosis (ALS), that results from mutations in the superoxide dismutase (SOD1) gene. DM occurs in many dog breeds, including the Pembroke Welsh Corgi and Boxer. The initial upper motor neuron degeneration produces spastic paraparesis and affected dogs develop general proprioceptive ataxia in the pelvic limbs. Dog owners usually elect euthanasia when their dog becomes paraplegic. When euthanasia is delayed, lower motor neuron signs including ascending tetraparesis, flaccid paralysis and widespread muscle atrophy emerge. For this study, muscle and peripheral nerve specimens were evaluated at varying disease stages from DM-affected Pembroke Welsh Corgis and Boxers that were homozygous for the SOD1 mutation and had spinal cord histopathology consistent with DM. Comparisons were made with age- and breed-matched control dogs. Here we provide evidence that Pembroke Welsh Corgis and Boxers with chronic DM develop muscle atrophy consistent with denervation, peripheral nerve pathology consistent with an axonopathy, and to a lesser degree demyelination. Canine DM has been proposed as a potential spontaneous animal disease model of human ALS. The results of this study provide further support that canine DM recapitulates one form of the corresponding human disorder and should serve as a valuable animal model to develop therapeutic strategies. PMID:22542607

  9. [Orofacial pain - Trigeminal neuralgia and posttraumatic trigeminal neuropathy: Common features and differences].

    PubMed

    Thieme, V

    2016-02-01

    Neuropathic pain is the result of a lesion or disease of the somatosensory system in the peripheral or central nervous system. Classical trigeminal neuralgia and posttraumatic trigeminal neuropathy are pain disorders which oral and maxillofacial surgeons and dentists are confronted with in the differential diagnostics in routine daily practice. The etiopathogenesis of classical trigeminal neuralgia is attributable to pathological blood vessel-nerve contact in the trigeminal nerve root entry zone to the brain stem. The typical pain symptoms are characterized by sudden stabbing pain attacks. The pharmaceutical prophylaxis is based on the individually titrated administration of anticonvulsant drugs. The indications for interventional treatment are dependent on the course, response to drug treatment, resilience and wishes of the patient. The neuropathic mechanism of posttraumatic trigeminal neuropathy originates from nerve damage, which leads to peripheral and central sensitization with lowering of the pain threshold and multiple somatosensory disorders. The prophylaxis consists of avoidance of excessive acute and long-lasting pain stimuli. Against the background of the biopsychosocial pain model, the treatment of posttraumatic trigeminal neuropathy necessitates a multimodal, interdisciplinary concept. PMID:26815785

  10. Electrophysiological investigation of toxic neuropathies.

    PubMed

    Le Quesne, P M

    1982-01-01

    Electrophysiological changes are correlated with pathological processes. Marked slowing of conduction is found in segmental demyelination due to delayed nodal excitation or short lengths of continuous conduction. Secondary demyelination causes slow conduction in hexacarbon neuropathy. Slight reduction in maximal conduction velocity is attributable to selective damage to large fibres in acrylamide neuropathy. Sensory nerve action potential amplitude is a sensitive measure of peripheral nerve function and comparison of abnormalities in different nerve segments may indicate the nature of the underlying pathological change. Other abnormalities may be elucidated by double stimuli; eg repetitive activity due to cholinesterase inhibition only occurs after the first of two closely spaced stimuli. Activity-related excitability changes may be detected by measuring the amplitude of the response to a submaximal stimulus at varying times after a maximal shock and is increased and prolonged by the pyrethroid deltamethrin. PMID:6962658

  11. The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms

    NASA Technical Reports Server (NTRS)

    Suarez, G. A.; Opfer-Gehrking, T. L.; Offord, K. P.; Atkinson, E. J.; O'Brien, P. C.; Low, P. A.

    1999-01-01

    OBJECTIVE: To develop a new specific instrument called the Autonomic Symptom Profile to measure autonomic symptoms and test its validity. BACKGROUND: Measuring symptoms is important in the evaluation of quality of life outcomes. There is no validated, self-completed questionnaire on the symptoms of patients with autonomic disorders. METHODS: The questionnaire is 169 items concerning different aspects of autonomic symptoms. The Composite Autonomic Symptom Scale (COMPASS) with item-weighting was established; higher scores indicate more or worse symptoms. Autonomic function tests were performed to generate the Composite Autonomic Scoring Scale (CASS) and to quantify autonomic deficits. We compared the results of the COMPASS with the CASS derived from the Autonomic Reflex Screen to evaluate validity. RESULTS: The instrument was tested in 41 healthy controls (mean age 46.6 years), 33 patients with nonautonomic peripheral neuropathies (mean age 59.5 years), and 39 patients with autonomic failure (mean age 61.1 years). COMPASS scores correlated well with the CASS, demonstrating an acceptable level of content and criterion validity. The mean (+/-SD) overall COMPASS score was 9.8 (+/-9) in controls, 25.9 (+/-17.9) in the patients with nonautonomic peripheral neuropathies, and 52.3 (+/-24.2) in the autonomic failure group. Scores of symptoms of orthostatic intolerance and secretomotor dysfunction best predicted the CASS on multiple stepwise regression analysis. CONCLUSIONS: We describe a questionnaire that measures autonomic symptoms and present evidence for its validity. The instrument shows promise in assessing autonomic symptoms in clinical trials and epidemiologic studies.

  12. Neuropathy secondary to drugs

    MedlinePlus

    Neuropathy secondary to drugs is a loss of sensation or movement in a part of the body ... weakness. Many medicines may affect the development of neuropathy, including: Heart or blood pressure drugs: Amiodarone Hydralazine ...

  13. Neuropathy secondary to drugs

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000700.htm Neuropathy secondary to drugs To use the sharing features on this page, please enable JavaScript. Neuropathy secondary to drugs is a loss of sensation ...

  14. Comorbid anxiety-like behavior and locus coeruleus impairment in diabetic peripheral neuropathy: A comparative study with the chronic constriction injury model.

    PubMed

    Alba-Delgado, Cristina; Cebada-Aleu, Alberto; Mico, Juan Antonio; Berrocoso, Esther

    2016-11-01

    Anxiety frequently appears in patients with diabetic neuropathic pain, a highly prevalent clinical condition. However, the neurobiological mechanisms of this comorbidity are poorly known. Anxiogenic phenotype has been associated with alterations of the noradrenergic locus coeruleus (LC) after peripheral nerve entrapment. We have examined the sensorial (pain) and affective (anxiety) behaviors, and the LC activity in streptozotocin (STZ)-induced diabetic rats. A comparative study with the chronic constriction injury (CCI) model of sciatic nerve was also carried out. Diabetic nociceptive hypersensitivity was observed to appear gradually, reaching their maximum at fourth week. In contrast, CCI displayed a sharp decrease in their sensorial threshold at seventh day. In both models, anxiety-like phenotype was evident after four weeks but not earlier, coincident with the LC alterations. Indeed, STZ animals showed reduced LC firing activity, tyrosine hydroxylase, pCREB and noradrenaline transporter levels, contrary to observed in CCI animals. However, in both models, enhanced LC alpha2-adrenoceptor sensitivity was presented at this time point. This study demonstrated that diabetes induced anxiety-like behavior comorbid with LC impairment at long-term. However, the nociceptive sensitivity time-course, as well as the LC functions, showed distinct features compared to the CCI model, indicating that specific neuroplastic mechanisms are at play in every model. PMID:27328428

  15. Inherited Neuropathies

    PubMed Central

    Li, Jun

    2013-01-01

    With a prevalence of 1 in 2500 people, inherited peripheral nerve diseases, collectively called Charcot-Marie-Tooth disease (CMT), are among the most common inherited neurologic disorders. Patients with CMT typically present with chronic muscle weakness and atrophy in limbs, sensory loss in the feet and hands, and foot deformities. Clinical similarities between patients often require genetic testing to achieve a precise diagnosis. In this article, the author reviews the clinical and pathologic features of CMT, and demonstrates how electrodiagnostic and genetic tools are used to assist in the diagnosis and symptomatic management of the diseases. Several cases are presented to illustrate the diagnostic processes. PMID:23117945

  16. Treatment of gastrointestinal autonomic neuropathy.

    PubMed

    Törnblom, Hans

    2016-03-01

    The symptoms caused by gastrointestinal autonomic neuropathy in diabetes mellitus is important to highlight since it affects a large proportion of people with diabetes, regardless of whether this is type 1 or type 2. Gastroparesis and general signs of bowel dysfunction, such as constipation, diarrhoea and abdominal pain are most often encountered and involve both pharmacological and non-pharmacological treatment options. This mini-review summarises a presentation given at the 'Diagnosis and treatment of autonomic diabetic neuropathy in the gut' symposium at the 2015 annual meeting of the EASD. It is accompanied by another mini-review on a topic from this symposium (by Azpiroz and Malagelada, DOI: 10.1007/s00125-015-3831-1 ) and a commentary by the Session Chair, Péter Kempler (DOI: 10.1007/s00125-015-3826-y ). PMID:26634570

  17. An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy

    PubMed Central

    Achilli, Francesca; Bros-Facer, Virginie; Williams, Hazel P.; Banks, Gareth T.; AlQatari, Mona; Chia, Ruth; Tucci, Valter; Groves, Michael; Nickols, Carole D.; Seburn, Kevin L.; Kendall, Rachel; Cader, Muhammed Z.; Talbot, Kevin; van Minnen, Jan; Burgess, Robert W.; Brandner, Sebastian; Martin, Joanne E.; Koltzenburg, Martin; Greensmith, Linda; Nolan, Patrick M.; Fisher, Elizabeth M. C.

    2009-01-01

    SUMMARY Mutations in the enzyme glycyl-tRNA synthetase (GARS) cause motor and sensory axon loss in the peripheral nervous system in humans, described clinically as Charcot-Marie-Tooth type 2D or distal spinal muscular atrophy type V. Here, we characterise a new mouse mutant, GarsC201R, with a point mutation that leads to a non-conservative substitution within GARS. Heterozygous mice with a C3H genetic background have loss of grip strength, decreased motor flexibility and disruption of fine motor control; this relatively mild phenotype is more severe on a C57BL/6 background. Homozygous mutants have a highly deleterious set of features, including movement difficulties and death before weaning. Heterozygous animals have a reduction in axon diameter in peripheral nerves, slowing of nerve conduction and an alteration in the recovery cycle of myelinated axons, as well as innervation defects. An assessment of GARS levels showed increased protein in 15-day-old mice compared with controls; however, this increase was not observed in 3-month-old animals, indicating that GARS function may be more crucial in younger animals. We found that enzyme activity was not reduced detectably in heterozygotes at any age, but was diminished greatly in homozygous mice compared with controls; thus, homozygous animals may suffer from a partial loss of function. The GarsC201R mutation described here is a contribution to our understanding of the mechanism by which mutations in tRNA synthetases, which are fundamentally important, ubiquitously expressed enzymes, cause axonopathy in specific sets of neurons. PMID:19470612

  18. Entrapment neuropathies III: lower limb.

    PubMed

    Beltran, Luis S; Bencardino, Jenny; Ghazikhanian, Varand; Beltran, Javier

    2010-11-01

    Clinicians frequently encounter compressive neuropathies of the lower extremity. The clinical history and physical examination, along with electrodiagnostic testing and imaging studies, lead to the correct diagnosis. The imaging characteristics of the compression neuropathies can include acute and chronic changes in the nerves and the muscles they innervate. We provide a detailed review of compression neuropathies of the lower extremity with an emphasis on magnetic resonance (MR) imaging characteristics. We discuss the clinical presentation, etiology, anatomical location, and MR imaging appearance of these neuropathies, including the piriformis syndrome, iliacus syndrome, saphenous neuropathy, obturator neuropathy, lateral femoral cutaneous neuropathy (meralgia paresthetica), proximal tibial neuropathy, common peroneal neuropathy, deep peroneal neuropathy, superficial peroneal neuropathy, tarsal tunnel syndrome, Baxter's neuropathy, jogger's foot, sural neuropathy, and Morton's neuroma. PMID:21072728

  19. [Electron microscopy as a tool for the diagnosis of neuropathies].

    PubMed

    Vallat, Jean-Michel; Richard, Laurence; Sindou, Philippe; Magy, Laurent

    2008-12-01

    Ultrastructural examination of a peripheral nerve biopsy may be particularly useful and sometimes indispensable for identification of the type of nerve lesion and of the aetiologies of peripheral neuropathies. The ultrastructural findings have, anyway, to be correlated with the clinical findings, the electrophysiological examination and the laboratory investigations. In this presentation, the various causes of peripheral neuropathies for which nerve biopsy study by electron microscope can provide diagnostic information are discussed. The principal aetiologies that will benefit from such an ultrastructural study are toxic, infectious, haemopathic and storage disorders. Chiefly for Charcot-Marie-Tooth sporadic cases, there are still indications for nerve biopsy to orientate diagnostic research in molecular biology. Sometimes, the electron microscopic examination will help to determine not only the cause of the peripheral neuropathy, but also the mechanism of nerve lesions which may induce specific and efficient treatments. PMID:19084717

  20. Hereditary neuropathy with liability to pressure palsies and amyotrophic lateral sclerosis.

    PubMed

    Bhatt, Archit; Farooq, Muhammad U; Aburashed, Rany; Kassab, Mounzer Y; Majid, Arshad; Bhatt, Shaila; Naravetla, Bharath; Dhaliwal, Gurmail

    2009-06-01

    A 56-year-old male with recurrent painless focal neuropathies and a family history of peripheral neuropathy of unknown etiology presented with progressively worsening of impaired sensations and weakness in his lower extremities. His initial electrodiagnostic evaluation was suggestive of severe sensory and motor peripheral polyneuropathy. The genetic testing was performed for familial causes of peripheral neuropathy as there was a family history of peripheral neuropathy of unknown etiology. The patient was found to have 1.5-Mb deletion in the PMP22 gene which was confirmatory of hereditary neuropathy with liability to pressure palsies (HNPP). He developed progressive upper and lower extremity weakness, bulbar dysfunction and widespread fasciculations during the course of his illness. He was subsequently diagnosed with amyotrophic lateral sclerosis (ALS). This is the second reported case of HNPP associated with ALS. We discuss significant clinical and electrodiagnostic findings of this interesting case. PMID:19238316

  1. Rheumatoid neuropathy: a histological and electrophysiological study

    PubMed Central

    Weller, R. O.; Bruckner, F. E.; Chamberlain, M. Anne

    1970-01-01

    Peripheral nerves in five patients with rheumatoid neuropathy were examined electrophysiologically and by sural nerve biopsy. There was close correlation between the clinical severity of the disease and the degree of nerve damage found histologically and by EMG. Group 1 patients with a mild distal sensory neuropathy showed varying degrees of axonal degeneration in the large myelinated fibres and some segmental demyelination. Group 2 patients with a severe, rapidly progressive sensori-motor neuropathy had extensive loss of myelinated fibres. In one case all the large fibres had degenerated. The second case had lost both large and small myelinated fibres together with many of the non-myelinated axons. The major nerve damage in both groups appeared to be axonal degeneration but some segmental demyelination was detected. Occlusive vascular disease in the vasa nervorum was considered to be the major cause of the nerve damage. Images PMID:4320255

  2. Mechanisms-based classifications of musculoskeletal pain: part 2 of 3: symptoms and signs of peripheral neuropathic pain in patients with low back (± leg) pain.

    PubMed

    Smart, Keith M; Blake, Catherine; Staines, Anthony; Thacker, Mick; Doody, Catherine

    2012-08-01

    As a mechanisms-based classification of pain 'peripheral neuropathic pain' (PNP) refers to pain arising from a primary lesion or dysfunction in the peripheral nervous system. Symptoms and signs associated with an assumed dominance of PNP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of PNP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol. Patients' pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of two symptoms and one sign predictive of PNP, including: 'Pain referred in a dermatomal or cutaneous distribution', 'History of nerve injury, pathology or mechanical compromise' and 'Pain/symptom provocation with mechanical/movement tests (e.g. Active/Passive, Neurodynamic) that move/load/compress neural tissue'. This cluster was found to have high levels of classification accuracy (sensitivity 86.3%, 95% CI: 78.0-92.3; specificity 96.0%, 95% CI: 93.4-97.8; diagnostic odds ratio 150.9, 95% CI: 69.4-328.1). Pattern recognition of this empirically-derived cluster of symptoms and signs may help clinicians identify an assumed dominance of PNP mechanisms in patients with low back pain disorders in a way that might usefully inform subsequent patient management. PMID:22465002

  3. Diabetic Neuropathies: The Nerve Damage of Diabetes

    MedlinePlus

    ... falling in response to normal body functions and physical activity. Digestive System Nerve damage to the digestive system most commonly ... neuropathy on the basis of symptoms and a physical exam. During the exam, the doctor ... temperature, or light touch. Foot Exams Experts recommend ...

  4. Pathogenesis and treatment of immune-mediated neuropathies.

    PubMed

    Lehmann, Helmar C; Meyer Zu Horste, Gerd; Kieseier, Bernd C; Hartung, Hans-Peter

    2009-07-01

    Immune-mediated neuropathies represent a heterogeneous spectrum of peripheral nerve disorders that can be classified according to time course, predominant involvement of motor/sensory fibers, distribution of deficits and paraclinical parameters such as electrophysiology and serum antibodies. In the last few years, significant advances have been achieved in elucidating underlying pathomechanisms, which made it possible to identify potential therapeutic targets. In this review, we discuss the latest development in pathogenesis and treatment of immune-mediated neuropathies. PMID:21179533

  5. An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome.

    PubMed

    Jacobs, J M; Wilson, J

    1992-01-01

    We present clinical and laboratory data from a patient with Waardenburg's syndrome type II comprising iris heterochromia and deafness, complicated by Hirschsprung's disease--a known association--and an unusual demyelinating peripheral neuropathy--a unique association. The neuropathy is characterised by excessive focal folding of myelin sheaths. It is our view that, although both disorders could represent the consequences of neural crest embryopathy, it is more likely that they are associated by chance. PMID:1636383

  6. Inherited mitochondrial neuropathies.

    PubMed

    Finsterer, Josef

    2011-05-15

    Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations. MIDs in which polyneuropathy is an inconstant feature among others is the MELAS syndrome, MERRF syndrome, LHON, Mendelian PEO, KSS, Leigh syndrome, MNGIE, SANDO; MIRAS, MEMSA, AHS, MDS (hepato-cerebral form), IOSCA, and ADOA syndrome. In the majority of the cases polyneuropathy presents in a multiplex neuropathy distribution. Nerve conduction studies may reveal either axonal or demyelinated or mixed types of neuropathies. If a hereditary neuropathy is due to mitochondrial dysfunction, the management of these patients is at variance from non-mitochondrial hereditary neuropathies. Patients with mitochondrial hereditary neuropathy need to be carefully investigated for clinical or subclinical involvement of other organs or systems. Supportive treatment with co-factors, antioxidants, alternative energy sources, or lactate lowering agents can be tried. Involvement of other organs may require specific treatment. Mitochondrial neuropathies should be included in the differential diagnosis of hereditary neuropathies. PMID:21402391

  7. Pathogenesis of immune-mediated neuropathies.

    PubMed

    Dalakas, Marinos C

    2015-04-01

    Autoimmune neuropathies occur when immunologic tolerance to myelin or axonal antigens is lost. Even though the triggering factors and the underling immunopathology have not been fully elucidated in all neuropathy subsets, immunological studies on the patients' nerves, transfer experiments with the patients' serum or intraneural injections, and molecular fingerprinting on circulating autoantibodies or autoreactive T cells, indicate that cellular and humoral factors, either independently or in concert with each other, play a fundamental role in their cause. The review is focused on the main subtypes of autoimmune neuropathies, mainly the Guillain-Barré syndrome(s), the Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), the Multifocal Motor Neuropathy (MMN), and the IgM anti-MAG-antibody mediated neuropathy. It addresses the factors associated with breaking tolerance, examines the T cell activation process including co-stimulatory molecules and key cytokines, and discusses the role of antibodies against peripheral nerve glycolipids or glycoproteins. Special attention is given to the newly identified proteins in the nodal, paranodal and juxtaparanodal regions as potential antigenic targets that could best explain conduction failure and rapid recovery. New biological agents against T cells, cytokines, B cells, transmigration and transduction molecules involved in their immunopathologic network, are discussed as future therapeutic options in difficult cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. PMID:24949885

  8. Neuropathy of nitroimidazole radiosensitizers: clinical and pathological description

    SciTech Connect

    Wasserman, T.H.; Nelson, J.S.; VonGerichten, D.

    1984-09-01

    The dose limiting toxicity of the nitroimidazole radiosensitizers is peripherial neuropathy. Improved pharmacology of newer drugs has eliminated the encephalopathy. Peripheral neuropathies are predominently mild to moderate paresthesias of both hands and feet. Subjective changes occur with or without minimal objective changes on neurologic exam. All of the neuropathies occurred within 30 days of the last drug dose and are of varible duration. Sural nerve biopsies from patients indicate progressive axonal degeneration affecting both large and small caliber myelinated fibers. Axonal damage appears to be more severe in the distal portion of the nerves. More data are needed for correlation of clinical and pathological changes.

  9. Retinoic acid reduces solvent-induced neuropathy and promotes neural regeneration in mice.

    PubMed

    Palencia, Guadalupe; Hernández-Pedro, Norma; Saavedra-Perez, David; Peña-Curiel, Omar; Ortiz-Plata, Alma; Ordoñez, Graciela; Flores-Estrada, Diana; Sotelo, Julio; Arrieta, Oscar

    2014-08-01

    In humans, exposure to organic solvents (OS) is frequent in work activities or as a recreational inhalant, inducing severe neuropathy (secondary to demyelization of peripheral nerves). We have previously shown that all-trans retinoic acid (ATRA) increases local content of neural growth factor (NGF), improving peripheral neuropathy of diverse origins. In this study, we evaluated the effect of ATRA on OS-induced peripheral neuropathy in experimental mice. Two simultaneous experiments were performed. The first one aimed to evaluate ATRA for the prevention of damage induced by OS, the second to test ATRA as an OS-induced neuropathy treatment. Nociceptive threshold latency and NGF concentration in serum and in peripheral nerves were determined. Morphological changes and evidence of sciatic nerve regeneration were evaluated. Mice exposed to OS developed neuropathy and axonal degeneration. ATRA diminished the effects of OS inhalation on sensorial changes and nerve morphology. Treatment with ATRA reversed sensorial and nerve morphological changes of OS-induced neuropathy, and this was associated with increased contents of NGF. Similar to previous experiences on diabetic and toxic neuropathy, ATRA reduced and partially reversed the peripheral neuropathy caused by OS exposure. These favorable effects apparently are due to local production of NGF induced by neural regeneration in response to the administration of retinoic acid. PMID:24647975

  10. Hereditary neuropathy with liability to pressure palsies: the first publication (1947).

    PubMed

    Koehler, Peter J

    2003-04-01

    The first report of hereditary neuropathy with liability to pressure palsies (HNPP) was published in Dutch in 1947. The present paper makes it accessible in the English language. de Jong described two families, but only the cases from the first family may be considered to have had HNPP. Five persons from three generations had recurring peripheral neuropathies. de Jong hypothesized a hereditary disposition for the occurrence of neuropathies, but suggested a relationship with low vitamin B(1) levels. PMID:12682341

  11. Painful Traumatic Trigeminal Neuropathy.

    PubMed

    Rafael, Benoliel; Sorin, Teich; Eli, Eliav

    2016-08-01

    This article discusses neuropathic pain of traumatic origin affecting the trigeminal nerve. This syndrome has been termed painful traumatic trigeminal neuropathy by the International Headache Society and replaces atypical odontalgia, deafferentation pain, traumatic neuropathy, and phantom toothache. The discussion emphasizes the diagnosis and the early and late management of injuries to the trigeminal nerve and subsequent painful conditions. PMID:27475512

  12. Diagnosis and Treatment of Pain in Small Fiber Neuropathy

    PubMed Central

    Hovaguimian, Alexandra

    2011-01-01

    Small fiber neuropathy manifests in a variety of different diseases and often results in symptoms of burning pain, shooting pain, allodynia, and hyperesthesia. Diagnosis of small fiber neuropathy is determined primarily by the history and physical exam, but functional neurophysiologic testing and skin biopsy evaluation of intraepidermal nerve fiber density can provide diagnostic confirmation. Management of small fiber neuropathy depends on the underlying etiology with concurrent treatment of associated neuropathic pain. A variety of recent guidelines propose the use of antidepressants, anticonvulsants, opioids, topical therapies, and nonpharmacologic treatments as part of the overall management of neuropathic pain. Unfortunately, little data about the treatment of pain specifically in small fiber neuropathy exist because most studies combine mixed neuropathic pain syndromes in the analysis. Additional studies targeting the treatment of pain in small fiber neuropathy are needed to guide decision making. PMID:21286866

  13. Hereditary neuropathy with liability to pressure palsies occurring during military training.

    PubMed

    Delacour, H; Bompaire, F; Biale, L; Sallansonnet-Froment, M; Ceppa, F; Burnat, P

    2012-03-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant peripheral neuropathy characterized by recurrent isolated nerve palsies, which are precipitated by trivial compression and trauma. Although HNPP has been well-described in literature, it often goes unrecognized. We report a case of HNPP occurring during military training to promote recognition and proper management of this entity. PMID:22545374

  14. Guillain Barré syndrome and other immune mediated neuropathies: diagnosis and classification.

    PubMed

    Eldar, Adi Hersalis; Chapman, Joab

    2014-01-01

    Immune mediated neuropathies are uncommon but important to diagnose because they are potentially treatable. This chapter summarizes the clinical approach to diagnosis of Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and related neuropathies which are thought to be caused by direct autoimmune attack on peripheral nerves. PMID:24434363

  15. Identifying Common Genetic Risk Factors of Diabetic Neuropathies

    PubMed Central

    Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879

  16. Neuropathy associated with chronic low level exposure to n-hexane

    SciTech Connect

    Ruff, R.L.; Petito, C.K.; Acheson, L.S.

    1981-05-01

    Concentrations of n-hexane greater than the threshold limit value (TLV) of 500 ppm are known to produce peripheral neuropathy. This report describes the case of a worker who developed peripheral neuropathy, with a histologic pattern characteristic of n-hexane toxicity, after chronic on-the-job exposure to n-hexane at concentrations less than 450 ppm. We suggest that the current TLV for n-hexane be reevaluated.

  17. Tumor necrosis factor-alpha antagonists and neuropathy.

    PubMed

    Stübgen, Joerg-Patrick

    2008-03-01

    Tumor necrosis factor (TNF)-alpha plays an important role in many aspects of immune system development, immune-response regulation, and T-cell-mediated tissue injury. The evidence that TNF-alpha, released by autoreactive T cells and macrophages, may contribute to the pathogenesis of immune-mediated demyelinating neuropathies is reviewed. TNF-alpha antagonists (infliximab, etanercept, adalimumab) are indicated for the treatment of advanced inflammatory rheumatic and bowel disease, but these drugs can induce a range of autoimmune diseases that also attack the central and peripheral nervous systems. Case histories and series report on the association between anti-TNF-alpha treatment and various disorders of peripheral nerve such as Guillain-Barré syndrome, Miller Fisher syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy with conduction block, mononeuropathy multiplex, and axonal sensorimotor polyneuropathies. The proposed pathogeneses of TNF-alpha-associated neuropathies include both a T-cell and humoral immune attack against peripheral nerve myelin, vasculitis-induced nerve ischemia, and inhibition of signaling support for axons. Most neuropathies improve over a period of months by withdrawal of the TNF-alpha antagonist, with or without additional immune-modulating treatment. Preliminary observations suggest that TNF-alpha antagonists may be useful as an antigen-nonspecific treatment approach to immune-mediated neuropathies in patients with a poor response to, or intolerance of, standard therapies, but further studies are required. PMID:18041052

  18. Transcriptomic analyses of genes and tissues in inherited sensory neuropathies.

    PubMed

    Sapio, Matthew R; Goswami, Samridhi C; Gross, Jacklyn R; Mannes, Andrew J; Iadarola, Michael J

    2016-09-01

    Inherited sensory neuropathies are caused by mutations in genes affecting either primary afferent neurons, or the Schwann cells that myelinate them. Using RNA-Seq, we analyzed the transcriptome of human and rat DRG and peripheral nerve, which contain sensory neurons and Schwann cells, respectively. We subdivide inherited sensory neuropathies based on expression of the mutated gene in these tissues, as well as in mouse TRPV1 lineage DRG nociceptive neurons, and across 32 human tissues from the Human Protein Atlas. We propose that this comprehensive approach to neuropathy gene expression leads to better understanding of the involved cell types in patients with these disorders. We also characterize the genetic "fingerprint" of both tissues, and present the highly tissue-specific genes in DRG and sciatic nerve that may aid in the development of gene panels to improve diagnostics for genetic neuropathies, and may represent specific drug targets for diseases of these tissues. PMID:27343803

  19. Temperature sensitive auditory neuropathy.

    PubMed

    Zhang, Qiujing; Lan, Lan; Shi, Wei; Yu, Lan; Xie, Lin-Yi; Xiong, Fen; Zhao, Cui; Li, Na; Yin, Zifang; Zong, Liang; Guan, Jing; Wang, Dayong; Sun, Wei; Wang, Qiuju

    2016-05-01

    Temperature sensitive auditory neuropathy is a very rare and puzzling disorder. In the present study, we reported three unrelated 2 to 6 year-old children who were diagnosed as auditory neuropathy patients who complained of severe hearing loss when they had fever. Their hearing thresholds varied from the morning to the afternoon. Two of these patients' hearing improved with age, and one patient received positive results from cochlear implant. Genetic analysis revealed that these three patients had otoferlin (OTOF) homozygous or compound heterozygous mutations with the genotypes c.2975_2978delAG/c.4819C>T, c.4819C>T/c.4819C>T, or c.2382_2383delC/c.1621G>A, respectively. Our study suggests that these gene mutations may be the cause of temperature sensitive auditory neuropathy. The long term follow up results suggest that the hearing loss in this type of auditory neuropathy may recover with age. PMID:26778470

  20. Ultrasound of Peripheral Nerves

    PubMed Central

    Suk, Jung Im; Walker, Francis O.; Cartwright, Michael S.

    2013-01-01

    Over the last decade, neuromuscular ultrasound has emerged as a useful tool for the diagnosis of peripheral nerve disorders. This article reviews sonographic findings of normal nerves including key quantitative ultrasound measurements that are helpful in the evaluation of focal and possibly generalized peripheral neuropathies. It also discusses several recent papers outlining the evidence base for the use of this technology, as well as new findings in compressive, traumatic, and generalized neuropathies. Ultrasound is well suited for use in electrodiagnostic laboratories where physicians, experienced in both the clinical evaluation of patients and the application of hands-on technology, can integrate findings from the patient’s history, physical examination, electrophysiological studies, and imaging for diagnosis and management. PMID:23314937

  1. Lower Limb Arteriovenous Communications in Diabetes Mellitus: A Potential Reason for Aggravation of Ischemic Symptoms

    SciTech Connect

    Hamady, Mohamad S.; Yu, Dominic F.; Sayer, Gabriel L.; Edmonds, Michael E.; Walters, Huw L.; Sidhu, Paul S.

    2006-10-15

    The aim of this study was to assess the prevalence and to evaluate the clinical associations of arteriovenous communications in patients with diabetes mellitus (DM) and lower limb peripheral arterial ischemia. Peripheral arteriography of DM patients from an eight-year period (1993-2000) was evaluated retrospectively by two observers. The presence of arteriovenous communications, defined as occurring without evidence of a preceding precipitating event, and the distribution and severity of the vascular disease were evaluated. The type (non-insulin-dependent DM or insulin-dependent DM) and the duration of the DM, the presenting symptoms, and the presence of a peripheral neuropathy were documented by a review of the clinical records. A total of 348 arteriography studies in 285 DM patients were evaluated (duration of DM: median, 16 years; range, 7-42 years); an arteriovenous communication was present in 14/285 patients (4.9%), 9 male and 5 female (median age, 71 years; range, 17-84 years). Symptoms were those of a peripheral leg ulcer (n = 11), claudication (n = 3), and gangrene (n = 1), with symptoms ipsilateral to the side of the arteriovenous communication in 13/14 patients. The sites of the arteriovenous communications were infra popliteal (n = 7), popliteal (n = 3), superficial femoral artery (n = 3), and common femoral artery (n = 1). Features of a peripheral neuropathy were found in 12/14 and ipsilateral to the side of the communication in 11/12. Arteriovenous communications in the peripheral femoral arterial system of patients with DM is an uncommon finding. Although not proven in the current study, arteriovenous communications might be associated with more severe symptoms than that attributable to the underlying vascular disease alone.

  2. Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence

    PubMed Central

    Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

    2016-01-01

    ABSTRACT Background: Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. Case presentation: A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. Discussion: CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. Conclusion: In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration. PMID:27105248

  3. [Ultrasonographic diagnosis of inflammatory neuropathies].

    PubMed

    Sugimoto, Takamichi; Ochi, Kazuhide; Hosomi, Naohisa; Matsumoto, Masayasu

    2014-03-01

    Ultrasonographic nerve enlargement has primarily been reported in patients with inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy, Guillain-Barre syndrome, vasculitic neuropathy and leprosy. Nerve ultrasonography is a promising diagnostic supportive tool for inflammatory neuropathies. The ultrasonographic findings that are currently useful are 1) nerve enlargement primarily suggests the existence of inflammatory or demyelinating neuropathies and 2) for patients with CIDP or demyelinating Charcot-Marie-Tooth disease, the pattern of nerve enlargement is noted, and this pattern is useful for discriminating between these diseases. More precise evidence of ultrasonographic findings for inflammatory neuropathies should be established in the future. PMID:24607946

  4. Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain

    PubMed Central

    Sagen, Jacqueline; Castellanos, Daniel A; Hama, Aldric T

    2016-01-01

    Background A consequence of HIV infection is sensory neuropathy, a debilitating condition that degrades the quality of life of HIV patients. Furthermore, life-extending antiretroviral treatment may exacerbate HIV sensory neuropathy. Analgesics that relieve other neuropathic pains show little or no efficacy in ameliorating HIV sensory neuropathy. Thus, there is a need for analgesics for people with this particular pain. While lidocaine is used in the management of painful peripheral neuropathies, another local anesthetic mepivacaine, with a potentially improved bioavailability, could be utilized for the management of HIV neuropathic pain. Methods The efficacy of topical anesthetics was evaluated in a preclinical rodent model of painful peripheral neuropathy induced by epineural administration of the HIV envelope protein gp120 delivered using saturated oxidized cellulose implanted around the sciatic nerve. Beginning at 2 weeks following gp120 administration, the effects of local anesthetics topically applied via gauze pads were tested on heat and mechanical hyperalgesia in the hind paw. Rats were tested using several concentrations of mepivacaine or lidocaine during the following 2 weeks. Results By 2 weeks following epineural gp120 implantation, the ipsilateral hind paw developed significant hypersensitivity to noxious pressure and heat hyperalgesia. A short-lasting, concentration-dependent amelioration of pressure and heat hyperalgesia was observed following topical application of mepivacaine to the ipsilateral plantar hind paw. By contrast, topical lidocaine ameliorated heat hyperalgesia in a concentration-dependent manner but not pressure hyperalgesia. Equipotent concentrations of mepivacaine and lidocaine applied topically to the tail of mice significantly increased tail withdrawal latencies in the tail flick test, demonstrating that both local anesthetics attenuate responding to a brief noxious stimulus. Conclusion These findings showed that mepivacaine, rather

  5. Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies

    PubMed Central

    Berthelot, Jade; Jiner, Jennifer; Perrin-Tricaud, Claire; Fernando, Ruani; Chrast, Roman; Lenaers, Guy

    2016-01-01

    Schwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth diseases, that are commonly associated with a process of demyelination. However, the early molecular events that trigger the demyelination program in these diseases remain unknown. Here, we used virally delivered fluorescent probes and in vivo time-lapse imaging in a mouse model of demyelination to investigate the underlying mechanisms of the demyelination process. We demonstrated that mitochondrial calcium released by voltage-dependent anion channel 1 (VDAC1) after sciatic nerve injury triggers Schwann cell demyelination via ERK1/2, p38, JNK, and c-JUN activation. In diabetic mice, VDAC1 activity was altered, resulting in a mitochondrial calcium leak in Schwann cell cytoplasm, thereby priming the cell for demyelination. Moreover, reduction of mitochondrial calcium release, either by shRNA-mediated VDAC1 silencing or pharmacological inhibition, prevented demyelination, leading to nerve conduction and neuromuscular performance recovery in rodent models of diabetic neuropathy and Charcot-Marie-Tooth diseases. Therefore, this study identifies mitochondria as the early key factor in the molecular mechanism of peripheral demyelination and opens a potential opportunity for the treatment of demyelinating peripheral neuropathies. PMID:26878172

  6. [2013: what's new in inflammatory neuropathies].

    PubMed

    Kuntzer, T

    2014-12-01

    Several high-quality publications were published in 2013 and some major trials studies were started. In Guillain-Barré syndrome, events included the launch of IGOS and a better understanding of diagnostic limits, the effect of influenza vaccination, and better care, but uncertainty remains about analgesics. A new mouse model was also described. In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), diagnostic pitfalls can be recalled. Our knowledge of underlying pathophysiological processes has improved, and the value of monitoring with function and deficit scores has been demonstrated. IVIG can sometimes be effective longer than expected, but CIDP remains sensitive to corticosteroids, particularly with the long-term beneficial effects of megadose dexamethasone. The impact of fingolimod remains to be demonstrated in an ongoing trial. Advances concerning multifocal motor neuropathy, inflammatory plexopathy, and neuropathy with anti -MAG activity are discussed but treatments already recognized as effective should not be changed. Imaging of peripheral nerve progresses. PMID:25459118

  7. β-Tubulin mutations that cause severe neuropathies disrupt axonal transport

    PubMed Central

    Niwa, Shinsuke; Takahashi, Hironori; Hirokawa, Nobutaka

    2013-01-01

    Microtubules are fundamental to neuronal morphogenesis and function. Mutations in tubulin, the major constituent of microtubules, result in neuronal diseases. Here, we have analysed β-tubulin mutations that cause neuronal diseases and we have identified mutations that strongly inhibit axonal transport of vesicles and mitochondria. These mutations are in the H12 helix of β-tubulin and change the negative charge on the surface of the microtubule. This surface is the interface between microtubules and kinesin superfamily motor proteins (KIF). The binding of axonal transport KIFs to microtubules is dominant negatively disrupted by these mutations, which alters the localization of KIFs in neurons and inhibits axon elongation in vivo. In humans, these mutations induce broad neurological symptoms, such as loss of axons in the central nervous system and peripheral neuropathy. Thus, our data identified the critical region of β-tubulin required for axonal transport and suggest a molecular mechanism for human neuronal diseases caused by tubulin mutations. PMID:23503589

  8. β-Tubulin mutations that cause severe neuropathies disrupt axonal transport.

    PubMed

    Niwa, Shinsuke; Takahashi, Hironori; Hirokawa, Nobutaka

    2013-05-15

    Microtubules are fundamental to neuronal morphogenesis and function. Mutations in tubulin, the major constituent of microtubules, result in neuronal diseases. Here, we have analysed β-tubulin mutations that cause neuronal diseases and we have identified mutations that strongly inhibit axonal transport of vesicles and mitochondria. These mutations are in the H12 helix of β-tubulin and change the negative charge on the surface of the microtubule. This surface is the interface between microtubules and kinesin superfamily motor proteins (KIF). The binding of axonal transport KIFs to microtubules is dominant negatively disrupted by these mutations, which alters the localization of KIFs in neurons and inhibits axon elongation in vivo. In humans, these mutations induce broad neurological symptoms, such as loss of axons in the central nervous system and peripheral neuropathy. Thus, our data identified the critical region of β-tubulin required for axonal transport and suggest a molecular mechanism for human neuronal diseases caused by tubulin mutations. PMID:23503589

  9. Compression neuropathy of the peroneal nerve secondary to a ganglion cyst.

    PubMed

    Greer-Bayramoglu, Rebecca J; Nimigan, André S; Gan, Bing Siang

    2008-01-01

    Peripheral neuropathies caused by ganglion cysts are rare, particularly in the lower extremities. The case of a 45-year-old man with a two-month history of foot drop and swelling in the region of the right fibular head is presented. Physical examination and electromyogram studies verified a peroneal nerve palsy. Magnetic resonance imaging revealed a lobulated, multilocular, cystic-appearing mass extending around the fibular neck. Surgical decompression of the nerve with removal of the mass and careful articular branch ligation was performed. Surgical pathology reports confirmed the diagnosis of a ganglion cyst. The patient regained full function within four months of the decompression. Pertinent findings on physical examination are discussed, as well as electromyogram and magnetic resonance imaging results. If symptoms persist, early surgical decompression (between the third and fourth months) is recommended. PMID:19721802

  10. Compression neuropathy of the peroneal nerve secondary to a ganglion cyst

    PubMed Central

    Greer-Bayramoglu, Rebecca J; Nimigan, André S; Gan, Bing Siang

    2008-01-01

    Peripheral neuropathies caused by ganglion cysts are rare, particularly in the lower extremities. The case of a 45-year-old man with a two-month history of foot drop and swelling in the region of the right fibular head is presented. Physical examination and electromyogram studies verified a peroneal nerve palsy. Magnetic resonance imaging revealed a lobulated, multilocular, cystic-appearing mass extending around the fibular neck. Surgical decompression of the nerve with removal of the mass and careful articular branch ligation was performed. Surgical pathology reports confirmed the diagnosis of a ganglion cyst. The patient regained full function within four months of the decompression. Pertinent findings on physical examination are discussed, as well as electromyogram and magnetic resonance imaging results. If symptoms persist, early surgical decompression (between the third and fourth months) is recommended. PMID:19721802

  11. Measurement of current perception thresholds using the Neurometer® – applicability in diabetic neuropathy

    PubMed Central

    INCEU, GEORGETA VICTORIA; VERESIU, IOAN ANDREI

    2015-01-01

    The incidence of diabetes mellitus is continuously growing worldwide, while the specific chronic complications that it induces have a negative impact on life expectancy andquality, entailing extremely high costs of healthcare services. Diabetic peripheral neuropathy is one of the most common chronic complications of diabetes, affecting almost half of diabetic people during life. This review aims at summarizing the evidence on the advantages and the usefulness of current perception threshold measurement for peripheral diabetic neuropathy assessment. Among the different methods used for the screening and diagnosis of diabetic neuropathy, measurement of current perception threshold using the Neurometer® has the ability to assess three sub-types of nerve fiber by producing transcutaneous electrical stimuli at frequencies of 2000, 250 and 5 Hz. Current evidence shows that this method provides a useful, noninvasive evaluation technique of patients with peripheral nervous system disorders, being able to detect neuropathy in the earliest and asymptomatic stages. PMID:26733741

  12. Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess.

    PubMed

    Ghavanini, Amer A; Kimpinski, Kurt

    2014-09-01

    Pyridoxine deficiency and excess have been implicated as a cause for peripheral neuropathy. As a result, unrelated neuropathies are often treated with pyridoxine based on questionable evidence. However, neurological practitioners frequently discourage patients from taking pyridoxine in excess of 50 mg/d given concerns around the development of a toxic sensory neuronopathy. There is no systematic review to support either of the 2 practices. To address this gap in knowledge, we reviewed the available literature on neuropathy attributed to pyridoxine deficiency and excess. Based on the current limited data, it can be concluded that very low doses of daily pyridoxine are required to prevent peripheral neuropathy. There is inadequate evidence to support routine pyridoxine supplementation in patients with disorders of peripheral nervous system. Supplementation with pyridoxine at doses greater than 50 mg/d for extended duration may be harmful and should be discouraged. PMID:25137514

  13. Partial Amelioration of Peripheral and Central Symptoms of Huntington’s Disease via Modulation of Lipid Metabolism

    PubMed Central

    Chen, Jane Y.; Tran, Conny; Hwang, Lin; Deng, Gang; Jung, Michael E.; Faull, Kym F.; Levine, Michael S.; Cepeda, Carlos

    2016-01-01

    Background Huntington’s disease (HD) is a fatal, inherited neurodegenerative disorder characterized by uncontrollable dance-like movements, as well as cognitive deficits and mood changes. A feature of HD is a metabolic disturbance that precedes neurological symptoms. In addition, brain cholesterol synthesis is significantly reduced, which could hamper synaptic transmission. Objective Alterations in lipid metabolism as a potential target for therapeutic intervention in the R6/2 mouse model of HD were examined. Methods Electrophysiological recordings in vitro examined the acute effects of cholesterol-modifying drugs. In addition, behavioral testing, effects on synaptic activity, and measurements of circulating and brain tissue concentrations of cholesterol and the ketone β-hydroxybutyrate (BHB), were examined in symptomatic R6/2 mice and littermate controls raised on normal chow or a ketogenic diet (KD). Results Whole-cell voltage clamp recordings of striatal medium-sized spiny neurons (MSNs) from symptomatic R6/2 mice showed increased frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) compared with littermate controls. Incubation of slices in cholesterol reduced the frequency of large-amplitude sIPSCs. Addition of BHB or the Liver X Receptor (LXR) agonist T0901317 reduced the frequency and amplitude of sIPSCs. Surprisingly, incubation in simvastatin to reduce cholesterol levels also decreased the frequency of sIPSCs. HD mice fed the KD lost weight more gradually, performed better in an open field, had fewer stereotypies and lower brain levels of cholesterol than mice fed a regular diet. Conclusions Lipid metabolism represents a potential target for therapeutic intervention in HD. Modifying cholesterol or ketone levels acutely in the brain can partially rescue synaptic alterations, and the KD can prevent weight loss and improve some behavioral abnormalities. PMID:27031732

  14. Multifocal motor neuropathy.

    PubMed

    Muley, Suraj Ashok; Parry, Gareth J

    2012-09-01

    Multifocal motor neuropathy (MMN) was first described in 1988 as a purely motor neuropathy affecting multiple motor nerves. The diagnosis was based entirely on demonstrating electrophysiological evidence of a conduction block (CB) that selectively affected motor axons, with sparing of sensory axons even through the site of motor CB. Subsequently, a similar disorder was reported but with absence of demonstrable CB on routine nerve conduction studies and there is still some debate as to whether MMN without CB is related to MMN. MMN is thought to be an inflammatory neuropathy related to an immune attack on motor nerves. The conventional hypothesis is that the primary pathology is segmental demyelination, but recent research raises the possibility of a primary axonopathy. Anti-GM1 antibodies can be found in some patients but it is unclear whether these antibodies are pathogenic. Intravenous immunoglobulin is the mainstay of treatment but other immunosuppressive treatments can also be effective. PMID:22743043

  15. POEMS syndrome with opticneuritis as initial symptom: a case report.

    PubMed

    Liu, Yuanyuan; Lu, Weiping; Zhang, Hong; Li, Xiang

    2015-08-01

    Polyneuropathy, Organomegaly, Endocrinopathy, M-protein and Skin changes syndrome is a rare paraneoplastic syndrome from a plasma cell dyscrasia, which most commonly presents with peripheral neuropathy. We report a 30-year-old female with blurred vision and vision loss as reasons for her initial treatment; the patient was diagnosed with bilateral opticneuritis. Five months later, the patient started to have lower extremity numbness and fatigue. Initial laboratory tests did not reveal positive monoclonal immunoglobulin. Therefore, simple peripheral neuropathy was considered for diagnosis, and the patient was treated in the Department of Neurology in our hospital; however, the symptom was not alleviated. Seven months later, the patient showed symptoms of cough, dyspnea, along with rough skin, pigmentation and drooping of both feet. Chest CT revealed bronchiectasis and infection of lungs, destruction of thoracic bones and ribs. Further examination indicated that the patient had splenomegaly, hypothyroidism and monoclonal IgA-λ chain zone, which led to a clear diagnosis of Polyneuropathy, Organomegaly, Endocrinopathy, M-protein and Skin changes syndrome. PMID:25820707

  16. Entrapment in anti myelin-associated glycoprotein neuropathy.

    PubMed

    Faber, Catharina G; Notermans, Nicolette C; Wokke, John H J; Franssen, Hessel

    2009-04-01

    Anti-myelin associated glycoprotein (MAG) neuropathy is a chronic disorder in which IgM antibodies react with Schwann cell glycoproteins, including MAG and peripheral myelin protein 22 (PMP22). Nerve conduction studies show features of axon loss and predominantly distal slowing consistent with demyelination. Because a genetic loss of PMP22 function yields hereditary neuropathy with liability to pressure palsies (HNPP), loss of PMP22 function due to anti- MAG antibodies may result in increased sensitivity to entrapment. We investigated this by performing standardized electrophysiological studies in 16 patients with anti-MAG neuropathy and 16 disease controls with genetically confirmed HNPP. Disproportionate slowing relative to adjacent segments occurred in similar proportions of patients with anti-MAG neuropathy and HNPP, and was of the same magnitude in each group. Affected were the elbow, carpal tunnel and the wrist-hand segments of the median and ulnar nerves. However, in anti-MAG neuropathy as compared to HNPP, absolute values of distal motor latencies and conduction velocities outside entrapment sites were slower and amplitudes were lower. In conclusion, increased sensitivity for entrapment may occur in anti-MAG neuropathy and contribute to part of the nerve damage. PMID:19306083

  17. Network analysis of gene expression in peripheral blood identifies mTOR and NF-κB pathways involved in antipsychotic-induced extrapyramidal symptoms.

    PubMed

    Mas, S; Gassó, P; Parellada, E; Bernardo, M; Lafuente, A

    2015-10-01

    To identify the candidate genes for pharmacogenetic studies of antipsychotic (AP)-induced extrapyramidal symptoms (EPS), we propose a systems biology analytical approach, based on protein-protein interaction network construction and functional annotation analysis, of changes in gene expression (Human Genome U219 Array Plate) induced by treatment with risperidone or paliperidone in peripheral blood. 12 AP-naïve patients with first-episode psychosis participated in the present study. Our analysis revealed that, in response to AP treatment, constructed networks were enriched for different biological processes in patients without EPS (ubiquitination, protein folding and adenosine triphosphate (ATP) metabolism) compared with those presenting EPS (insulin receptor signaling, lipid modification, regulation of autophagy and immune response). Moreover, the observed differences also involved specific pathways, such as anaphase promoting complex /cdc20, prefoldin/CCT/triC and ATP synthesis in no-EPS patients, and mammalian target of rapamycin and NF-κB kinases in patients with EPS. Our results showing different patterns of gene expression in EPS patients, offer new and valuable markers for pharmacogenetic studies. PMID:25623440

  18. High doses of cobalt induce optic and auditory neuropathy.

    PubMed

    Apostoli, Pietro; Catalani, Simona; Zaghini, Anna; Mariotti, Andrea; Poliani, Pietro Luigi; Vielmi, Valentina; Semeraro, Francesco; Duse, Sarah; Porzionato, Andrea; Macchi, Veronica; Padovani, Alessandro; Rizzetti, Maria Cristina; De Caro, Raffaele

    2013-09-01

    The adverse biological effects of continuous exposure to cobalt and chromium have been well defined. In the past, this toxicity was largely an industrial issue concerning workers exposed in occupational setting. Nevertheless, recent reports have described a specific toxicity mediated by the high levels of cobalt and chromium released by metallic prostheses, particularly in patients who had received hip implants. Clinical symptoms, including blindness, deafness and peripheral neuropathy, suggest a specific neurotropism. However, little is known about the neuropathological basis of this process, and experimental evidence is still lacking. We have investigated this issue in an experimental setting using New Zealand White rabbits treated with repeated intravenous injections of cobalt and chromium, alone or in combination. No evident clinical or pathological alterations were associated after chromium administration alone, despite its high levels in blood and tissue while cobalt-chromium and cobalt-treated rabbits showed clinical signs indicative of auditory and optic system toxicity. On histopathological examination, the animals showed severe retinal and cochlear ganglion cell depletion along with optic nerve damage and loss of sensory cochlear hair cells. Interestingly, the severity of the alterations was related to dosages and time of exposure. These data confirmed our previous observation of severe auditory and optic nerve toxicity in patients exposed to an abnormal release of cobalt and chromium from damaged hip prostheses. Moreover, we have identified the major element mediating neurotoxicity to be cobalt, although the molecular mechanisms mediating this toxicity still have to be defined. PMID:23069009

  19. Duplication at Xq28 involving IKBKG is associated with progressive macrocephaly, recurrent infections, ectodermal dysplasia, benign tumors, and neuropathy.

    PubMed

    van Asbeck, Ellyze; Ramalingam, Arivudainambi; Dvorak, Chris; Chen, Tian-Jian; Morava, Eva

    2014-07-01

    Duplications on Xq28 are common, although quite variable in size, but usually include the MECP2 gene. Here, we present a patient with a unique, small, 167-kb duplication at Xq28, not including MECP2. The most important gene in the duplicated region was IKBKG, mutations in which can cause a variety of distinct syndromes. Our patient's symptoms overlapped with different IKBKG-associated phenotypes, including hypohidrotic ectodermal dysplasia, incontinentia pigmenti, immunodeficiency, recurrent isolated invasive pneumococcal disease and anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis, and lymphedema. In addition, she also had peripheral neuropathy, gastroparesis and various benign tumors, but no intellectual disability. Mixed syndromal presentation in several patients with IKBKG defect implies that IKBKG-related phenotypes are more like a spectrum, rather than distinct syndromes. We also suggest our patient's multisystem phenotype to be a novel contiguous gene syndrome, in which the key features include immune deficiency, macrocephaly, skin abnormalities, gastroparesis, peripheral small-fiber neuropathy, and benign tumors. PMID:24721901

  20. [Diagnosis and therapy of auditory synaptopathy/neuropathy].

    PubMed

    Moser, T; Strenzke, N; Meyer, A; Lesinski-Schiedat, A; Lenarz, T; Beutner, D; Foerst, A; Lang-Roth, R; von Wedel, H; Walger, M; Gross, M; Keilmann, A; Limberger, A; Steffens, T; Strutz, J

    2006-11-01

    Pathological auditory brainstem responses (lack of responses, elevated thresholds and perturbed waveforms) in combination with present otoacoustic emissions are typical audiometric findings in patients with a hearing impairment that particularly affects speech comprehension or complete deafness. This heterogenous group of disorders first described as "auditory neuropathy" includes dysfunction of peripheral synaptic coding of sound by inner hair cells (synaptopathy) and/or of the generation and propagation of action potentials in the auditory nerve (neuropathy). This joint statement provides prevailing background information as well as recommendations on diagnosis and treatment. The statement focuses on the handling in the german language area but also refers to current international statements. PMID:17041780

  1. Somatostatin and counterregulatory hormone responses to hypoglycaemia in diabetics with and without autonomic neuropathy.

    PubMed

    Fernandez-Castaner, M; Webb, S; Levy, I; Rios, M; Casamitjana, R; Bergua, M; Figuerola, D; Rivera, F

    1985-04-01

    Blood glucose, somatostatin and counterregulatory hormone responses to an i.v. bolus of insulin were studied in insulin-dependent diabetics with different degrees of autonomic neuropathy, after 24 hours of optimised control with an artificial pancreas. There was no plasma catecholamine response in patients with a sympathetic autonomic neuropathy. A normal somatostatin response to hypoglycemia was absent in patients with autonomic neuropathy. Glucagon did not respond in diabetics, independently of the degree of neuropathy. In all diabetics, cortisol and GH were stimulated. Absence of warning symptoms was observed in patients with catecholamine deficiency. Despite different hormone behaviour, blood glucose fall and recovery were similar in all diabetic groups. It is concluded that the glucagon response to insulin hypoglycaemia is reduced in all type 1 longstanding diabetics, whereas catecholamine and somatostatin responses are only abolished in those with autonomic neuropathy. Patients with sympathetic neuropathy would be considered at increased risk severe hypoglycaemia. PMID:2861121

  2. Ulnar nerve entrapment neuropathy at the elbow: relationship between the electrophysiological findings and neuropathic pain

    PubMed Central

    Halac, Gulistan; Topaloglu, Pinar; Demir, Saliha; Cıkrıkcıoglu, Mehmet Ali; Karadeli, Hasan Huseyin; Ozcan, Muhammet Emin; Asil, Talip

    2015-01-01

    [Purpose] Ulnar nerve neuropathies are the second most commonly seen entrapment neuropathies of the upper extremities after carpal tunnel syndrome. In this study, we aimed to evaluate pain among ulnar neuropathy patients by the Leeds assessment of neuropathic symptoms and signs pain scale and determine if it correlated with the severity of electrophysiologicalfindings. [Subjects and Methods] We studied 34 patients with clinical and electrophysiological ulnar nerve neuropathies at the elbow. After diagnosis of ulnar neuropathy at the elbow, all patients underwent the Turkish version of the Leeds assessment of neuropathic symptoms and signs pain scale. [Results] The ulnar entrapment neuropathy at the elbow was classified as class-2, class-3, class-4, and class-5 (Padua Distal Ulnar Neuropathy classification) for 15, 14, 4, and 1 patient, respectively. No patient included in class-1 was detected. According to Leeds assessment of neuropathic symptoms and signs pain scale, 24 patients scored under 12 points. The number of patients who achieved more than 12 points was 10. Groups were compared by using the χ2 test, and no difference was detected. There was no correlation between the Leeds assessment of neuropathic symptoms and signs pain scale and electromyographic findings. [Conclusion] We found that the severity of electrophysiologic findings of ulnar nerve entrapment at the elbow did not differ between neuropathic and non-neuropathic groups as assessed by the Leeds assessment of neuropathic symptoms and signs pain scale. PMID:26311956

  3. Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients.

    PubMed

    Goullee, Hayley; Wadley, Antonia L; Cherry, Catherine L; Allcock, Richard J N; Black, Michael; Kamerman, Peter R; Price, Patricia

    2016-08-01

    HIV-associated sensory neuropathy (HIV-SN) is the most common neurological condition associated with HIV. HIV-SN has characteristics of an inflammatory pathology caused by the virus itself and/or by antiretroviral treatment (ART). Here, we assess the impact of single-nucleotide polymorphisms (SNPs) in a cluster of three genes that affect inflammation and neuronal repair: P2X7R, P2X4R and CAMKK2. HIV-SN status was assessed using the Brief Peripheral Neuropathy Screening tool, with SN defined by bilateral symptoms and signs. Forty-five SNPs in P2X7R, P2X4R and CAMKK2 were genotyped using TaqMan fluorescent probes, in DNA samples from 153 HIV(+) black Southern African patients exposed to stavudine. Haplotypes were derived using the fastPHASE algorithm, and SNP genotypes and haplotypes associated with HIV-SN were identified. Optimal logistic regression models included demographics (age and height), with SNPs (model p < 0.0001; R (2) = 0.19) or haplotypes (model p < 0.0001; R (2) = 0.18, n = 137 excluding patients carrying CAMKK2 haplotypes perfectly associated with SN). Overall, CAMKK2 exhibited the strongest associations with HIV-SN, with two SNPs and six haplotypes predicting SN status in black Southern Africans. This gene warrants further study. PMID:26785644

  4. Anti-allodynic effect of theoesberiven F in a vincristine-induced neuropathy model

    PubMed Central

    Bang, Seunguk; Kim, Yee Suk; Jeong, Sang Rok

    2016-01-01

    Allodynia is a main symptom of the peripheral neuropathy induced by vincristine treatment. Theoesberiven F, a combination of Melilotus extract and proxyphylline, is currently used for the treatment of inflammatory conditions due to its potent anti-inflammatory and analgesic properties. The anti-allodynic effect of theoesberiven F on mechanical and cold allodynia in a rat model of vincristine-induced neuropathy was investigated in the present study. Intraperitoneal vincristine injections were administered to male Sprague-Dawley rats at a dose of 0.1 mg/kg/day over 12 days (5 days of injection, a 2-day cessation and 5 days of injection). Rats that were allodynic following the vincristine injections were randomly allocated into four groups. Normal saline was injected into rats in the control group. Theoesberiven F (0.1, 0.25 and 0.5 mg/kg) was administered to rats in the three experimental groups, respectively. Mechanical and cold allodynia were measured at preadministration and at 15, 30, 60, 90, 120, 150 and 180 min following the intraperitoneal administration of normal saline or theoesberiven F. The decreased paw withdrawal threshold induced by vincristine injection was increased by theoesberiven F administration. The increased withdrawal frequency to cold stimuli developed by vincristine was reduced by theoesberiven F administration. The results of this study suggest that the administration of theoesberiven F may be beneficial in reducing the mechanical and cold allodynia developed during vincristine treatment. PMID:27446278

  5. Hereditary neuropathy with liability to pressure palsy: a brief review with a case report.

    PubMed

    Rana, Abdul Qayyum; Masroor, Mohamed Sufian

    2012-03-01

    Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) is an autosomal dominant disorder and is usually characterized by episodes of recurrent and painless focal motor and sensory peripheral mononeuropathy. This condition is usually localized around areas of entrapment (predominantly the wrists, knees, elbows, and shoulders). The genetic locus of the disease is chromosome 17p12. A deletion of the PMP22 gene results in the lack of peripheral myelin protein, a key component to the myelin sheet of peripheral nerves. However, this disease may be completely asymptomatic until an event, such as a minor trauma, triggers these episodes, as seen in our presented case report. The diagnosis of HNPP can be somewhat challenging, as other diseases, such as Charcot-Marie-Tooth disease type 1A (CMT) and Hereditary Neuralgic Amyotrophy (HNA) must be included in the differential diagnosis due to their overlapping clinical features. There are currently no treatments to cure the disease, but therapies seek to alleviate the symptoms and recurring episodes. PMID:22023293

  6. Neurological associations in auditory neuropathy spectrum disorder: Results from a tertiary hospital in South India

    PubMed Central

    Lepcha, Anjali; Chandran, Reni K.; Alexander, Mathew; Agustine, Ann Mary; Thenmozhi, K.; Balraj, Achamma

    2015-01-01

    Aims: To find out the prevalence and types of neurological abnormalities associated in auditory neuropathy spectrum disorder in a large tertiary referral center. Settings and Design: A prospective clinical study was conducted on all patients diagnosed with auditory neuropathy spectrum disorder in the ear, nose, and throat (ENT) and neurology departments during a 17-month period. Patients with neurological abnormalities on history and examination were further assessed by a neurologist to determine the type of disorder present. Results: The frequency of auditory neuropathy spectrum disorder was 1.12%. Sixty percent were found to have neurological involvement. This included cerebral palsy in children, peripheral neuropathy (PN), spinocerebellar ataxia, hereditary motor-sensory neuropathy, spastic paresis, and ponto-bulbar palsy. Neurological lesions did not present simultaneously with hearing loss in most patients. Sixty-six percent of patients with auditory neuropathy spectrum disorder were born of consanguineous marriages. Conclusions: There is a high prevalence of neurological lesions in auditory neuropathy spectrum disorder which has to be kept in mind while evaluating such patients. Follow-up and counselling regarding the appearance of neuropathies is therefore important in such patients. A hereditary etiology is indicated in a majority of cases of auditory neuropathy spectrum disorder. PMID:26019414