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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. Symptoms: Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

    Schneider, Bryan P; Hershman, Dawn L; Loprinzi, Charles

    2015-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a problematic, treatment-induced toxicity that has the potential to impact quality of life and limit the doses of curative intent therapy. This therapy-induced side effect is one of the most troublesome in oncology clinical practices, considering the morbidity, the frequency, and the potential irreversibility of this problem. Patients with breast cancer are particularly impacted by this side effect as multiple agents commonly used for this disease can cause neuropathy. In this chapter, we provide an overview of CIPN, including: clinical predictors, frequency, and its impact on quality of life. Further, we highlight the pathophysiology and review the literature to date for agents designed to prevent or treat CIPN. We also highlight the most important ongoing clinical and translational research questions that hope to help better predict and prevent this toxicity. This includes optimizing the methods of assessment, using host specific factors (Race and genetics) to predict those more likely to experience CIPN, and determining how CIPN might impact clinical decisions toward therapy.

  4. 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 ...

  5. Peripheral neuropathies.

    PubMed

    Hanewinckel, R; Ikram, M A; Van Doorn, P A

    2016-01-01

    Peripheral neuropathies are diseases of the peripheral nervous system that can be divided into mononeuropathies, multifocal neuropathies, and polyneuropathies. Symptoms usually include numbness and paresthesia. These symptoms are often accompanied by weakness and can be painful. Polyneuropathies can be divided into axonal and demyelinating forms, which is important for diagnostic reasons. Most peripheral neuropathies develop over months or years, but some are rapidly progressive. Some patients only suffer from mild, unilateral, slowly progressive tingling in the fingers due to median nerve compression in the wrist (carpal tunnel syndrome), while other patients can be tetraplegic, with respiratory insufficiency within 1-2 days due to Guillain-Barré syndrome. Carpal tunnel syndrome, with a prevalence of 5% and incidence of 1-2 per 1000 person-years, is the most common mononeuropathy. Population-based data for chronic polyneuropathy are relatively scarce. Prevalence is estimated at 1% and increases to 7% in persons over 65 years of age. Incidence is approximately 1 per 1000 person-years. Immune-mediated polyneuropathies like Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy are rare diseases, with an annual incidence of approximately 1-2 and 0.2-0.5 per 100 000 persons respectively. Most peripheral neuropathies are more prevalent in older adults and in men, except for carpal tunnel syndrome, which is more common in women. Diabetes is a common cause of peripheral neuropathy and is associated with both mono- and polyneuropathies. Among the group of chronic polyneuropathies, in about 20-25% no direct cause can be found. These are slowly progressive axonal polyneuropathies. PMID:27637963

  6. 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 ...

  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).

  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. 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 ...

  10. Peripheral neuropathy caused by methaqualone.

    PubMed

    Marks, P; Sloggem, J

    1976-01-01

    Three patients are described who each received methaqualone and developed signs and symptoms of peripheral neuropathy. The subsequent improvement after cessation of methaqualone was highly suggestive or a direct toxic action of the drug or one of its metabolites. In one patient methaqualone was recommended with reappearance of signs and symptoms of peripheral neuropathy. Again cessation of the drug caused disappearance of these signs. There was no evidence whatsoever of any electrolyte or metabolic disturbance or any other pathology which might have given rise to this symptom complex. In addition, no other drugs were prescribed besides methaqualone.

  11. 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

  12. Metabolic Correction in the Management of Diabetic Peripheral Neuropathy: Improving Clinical Results Beyond Symptom Control

    PubMed Central

    Miranda-Massari, Jorge R.; Gonzalez, Michael J.; Jimenez, Francisco J.; Allende-Vigo, Myriam Z.; Duconge, Jorge

    2013-01-01

    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, acetyi-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metforrnin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk

  13. 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

  14. Electrodiagnosis of peripheral neuropathy.

    PubMed

    Ross, Mark A

    2012-05-01

    Electrodiagnostic studies are an important component of the evaluation of patients with suspected peripheral nerve disorders. The pattern of findings and the features that are seen on the motor and sensory nerve conduction studies and needle electromyography can help to identify the type of neuropathy, define the underlying pathophysiology (axonal or demyelinating), and ultimately help to narrow the list of possible causes. This article reviews the electrodiagnostic approach to and interpretation of findings in patients with peripheral neuropathies.

  15. 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

  16. 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

  17. Inherited peripheral neuropathy.

    PubMed

    Keller, M P; Chance, P F

    1999-01-01

    Hereditary disorders of the peripheral nerves constitute a group of frequently encountered neurological diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is genetically heterogeneous and characterized by demyelination with moderately to severely reduced nerve conduction velocities, absent muscle stretch reflexes and onion bulb formation. Genetic loci for CMT1 map to chromosome 17 (CMT1A), chromosome 1 (CMT1B), and another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (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. CMT1 B result from point mutations in the myelin protein zero (Po or MPZ) gene. The molecular defect in CMT1 C is unknown. Mutations in the early growth response 2 gene (EGR2) are also associated with demyelinating neuropathy. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q, and 11q. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is characterized by normal or mildly reduced nerve conduction velocity with decreased amplitude and axonal loss without hypertrophic features. One form of CMT2 maps to chromosome 1 p36 (CMT2A), another to chromosome 3p (CMT2B) and another to 7p (CMT2D). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy that may be associated with point mutations in either the PMP22 gene or the Po gene and shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced

  18. Peripheral neuropathy in arsenic smelter workers.

    PubMed

    Feldman, R G; Niles, C A; Kelly-Hayes, M; Sax, D S; Dixon, W J; Thompson, D J; Landau, E

    1979-07-01

    We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.

  19. Arsenical peripheral neuropathy.

    PubMed

    Mathew, Liberty; Vale, Allister; Adcock, Jane E

    2010-02-01

    A 49-year-old white man returned urgently to the UK after spending 3 months in Goa. He had a several week history of vomiting, weight loss, a widespread desquamating skin rash, and symptoms and signs of a progressive painful sensorimotor neuropathy. He had a mild normocytic anaemia and lymphopenia. Nerve conduction studies revealed a severe predominantly axonal large fibre sensorimotor neuropathy, confirmed on subsequent sural nerve biopsy. Once he had left Goa most of his symptoms started to rapidly settle although the neuropathic symptoms remained severe. Arsenic poisoning was suspected. A spot urine arsenic concentration was 300 microg/l, confirming the diagnosis. He was treated with chelation therapy. Deliberate arsenic poisoning was highly likely.

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

    PubMed Central

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

    2012-01-01

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

  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.

  2. Vitamin B supplementation for diabetic peripheral neuropathy.

    PubMed

    Jayabalan, Bhavani; Low, Lian Leng

    2016-02-01

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

  3. 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 ...

  4. 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

  5. Mitochondria and peripheral neuropathies.

    PubMed

    Vital, Anne; Vital, Claude

    2012-12-01

    There has been considerable progress during the past 24 years in the molecular genetics of mitochondrial DNA and related nuclear DNA mutations, and more than 100 nerve biopsies from hereditary neuropathies related to mitochondrial cytopathy have been accurately examined. Neuropathies were first reported in diseases related to point mutations of mitochondrial DNA, but they proved to be a prominent feature of the phenotype in mitochondrial disorders caused by defects in nuclear DNA, particularly in 3 genes: polymerase gamma 1 (POLG1), mitofusin 2 (MFN2), and ganglioside-induced differentiation-associated protein 1 (GDAP1). Most patients have sensory-motor neuropathy, sometimes associated with ophthalmoplegia, ataxia, seizures, parkinsonism, myopathy, or visceral disorders. Some cases are caused by consanguinity, but most are sporadic with various phenotypes mimicking a wide range of other etiologies. Histochemistry on muscle biopsy, as well as identification of crystalloid inclusions at electron microscopy, may provide a diagnostic clue to mitochondriopathy, but nerve biopsy is often less informative. Nevertheless, enlarged mitochondria containing distorted or amputated cristae are highly suggestive, particularly when located in the Schwann cell cytoplasm. Also noticeable are clusters of regenerating myelinated fibers surrounded by concentric Schwann cell processes, and such onion bulb-like formations are frequently observed in neuropathies caused by GDAP1 mutations. PMID:23147504

  6. Endocrinologic causes of peripheral neuropathy. Pins and needles in a stocking-and-glove pattern and other symptoms.

    PubMed

    Perkins, A T; Morgenlander, J C

    1997-09-01

    In the Western world, diabetes is the biggest cause of peripheral neuropathy, usually distal symmetric polyneuropathy but some times another polyneuropathy or a focal neuropathy. In addition, hypothyroidism and acromegaly can cause carpal tunnel syndrome and other sensory complaints. A complete blood cell count, nerve-conduction tests, thyroid-function tests (needed in all patients with carpal tunnel syndrome), and when necessary, needle electromyography can help confirm the diagnosis. Treatment of underlying disease is the most successful management approach: Tight glucose control in diabetic patients, thyroid hormone replacement therapy in patients with hypothyroidism, and removal of the pituitary adenoma in patients with acromegaly are of proven benefit. Significant symptomatic relief of dysesthesias can be obtained with use of capsaicin cream, tricyclic antidepresants, anticonvulsant agents, or an antiarrhythmic drug.

  7. 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

  8. Axonopathy in peripheral neuropathies: Mechanisms and therapeutic approaches for regeneration.

    PubMed

    Landowski, Lila M; Dyck, P James B; Engelstad, JaNean; Taylor, Bruce V

    2016-10-01

    Peripheral neuropathies (PNs) are injuries or diseases of the nerves which arise from varied aetiology, including metabolic disease, trauma and drug toxicity. The clinical presentation depends on the type of neuropathy, and may include the loss of motor, sensory and autonomic functions, or development of debilitating neuropathic pain distal to the injury site. It can be challenging to identify the aetiology of PNs, as the clinical syndromes are often indistinct. However, the mechanisms that underlie pathological changes in peripheral neuropathy are fundamentally different, depending on the trigger. This review focuses on the axonopathy observed in two frequently encountered forms of peripheral neuropathy, diabetic neuropathy and chemotherapy-induced neuropathy. A key manifestation of axonopathy in PN is the degeneration of terminal arbors of peripheral nerves, resulting in a loss of epidermal nerve fibres and inappropriate termination of nerve endings. Many symptoms of PN arise from aberrant termination of nerve endings, and the underlying axonopathy may be non-reversible, as nerve regeneration after injury and disease is often poor, absent, or aberrant. Directed guidance of terminal arbors back into the epidermis is therefore a suggested approach to treat peripheral neuropathy. This review will outline potential strategies to enhance and guide axonal regeneration and reinnervation in the skin. Using diabetic neuropathy and chemotherapy-induced neuropathy as specific examples, this review examines the setbacks encountered with the translation of growth factors into therapeutics for human neuropathy, and suggests a number of approaches for topical drug delivery.

  9. Peripheral neuropathy: the importance of rare subtypes

    PubMed Central

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

    2016-01-01

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

  10. [Peripheral neuropathy caused by acute arsenic poisoning].

    PubMed

    Ramírez-Campos, J; Ramos-Peek, J; Martínez-Barros, M; Zamora-Peralta, M; Martínez-Cerrato, J

    1998-01-01

    Although peripheral neuropathy is a fairly common finding in chronic arsenic poisoning, little is known about the acute effects of this metal on peripheral nerves. This report shows clinical and electrophysiological findings in a patient who developed peripheral neuropathy only three days after a high-dose ingestion of this metal due to a failed suicide attempt. We speculate that peripheral nerves and some cranial nerves can show not only clinical but also subclinical involvement that can only be detected by neurophysiological studies.

  11. Pediatric peripheral neuropathy in proteus syndrome.

    PubMed

    Choi, M L; Wey, P D; Borah, G L

    1998-05-01

    Proteus syndrome is a rare congenital disorder comprised of subcutaneous and internal hamartomas, pigmented skin nevi, skull exostoses, hemihypertrophy, and macrodactyly of the hands and feet. A 5-year-old girl diagnosed with Proteus syndrome presented with distal median compression neuropathy with the primary complaint of severe pain involving the left hand. Surgical exploration of the hand revealed a lipofibromatous hamartoma of the median nerve. The transverse carpal ligament was released and epineurectomy of the median nerve was performed. The patient remains symptom free at the 9-month follow-up. This report is the first description of a hamartoma directly involving a peripheral nerve in Proteus syndrome. Decompression of the nerve with the removal of the fibrofatty neural sheath resulted in the resolution of the symptoms in this patient. The surgeon should consider this approach as a potential first line of treatment before a more radical resection of the nerve is contemplated. PMID:9600441

  12. 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

  13. 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

  14. 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.

  15. 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

  16. Peripheral neuropathy and antiretroviral drugs.

    PubMed

    Dalakas, M C

    2001-03-01

    Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy. Zidovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddl) and lamuvidine (3TC) cause neuropathy; stavudine (d4T) and fialuridine (FIAU) cause neuropathy or myopathy and lactic acidosis. The tissue distribution of phosphorylases responsible for phosphorylation of NRTIs relates to their selective tissue toxicity. The myopathy is characterized by muscle wasting, myalgia, fatigue, weakness and elevation of CK. The neuropathy is painful, sensory and axonal. In vitro, NRTIs inhibit the gamma-DNA polymerase, responsible for replication of mtDNA, and cause mtDNA dysfunction. In vivo, patients treated with AZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA depletion, deficiency of COX (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion, as determined with in vivo MRS spectroscopy, due to impaired oxidative phosphorylation. Animals or cultured cells treated with NRTIs develop neuropathy, myopathy, or cell destruction with similar changes in the mitochondria. There is evidence that the NRTI-related neuropathy is also due to mitochondrial toxicity. The NRTIs (AZT, ddC, ddl, d4T, 3TC) contain azido groups that compete with natural thymidine triphosphate as substrates of DNA pol-gamma and terminate mtDNA synthesis. In contrast, FIAU that contains 3'-OH groups serves as an alternate substrate for thymidine triphosphate with DNA pol-gamma and is incorporated into the DNA causing permanent mtDNA dysfunction. The NRTI-induced mitochondrial dysfunction has an influence on the clinical application of these agents, especially at high doses and when combined. They have produced in humans a new category of acquired mitochondrial toxins that cause clinical manifestations resembling the genetic mitochondrial disorders.

  17. Diabetic peripheral neuropathy: current perspective and future directions.

    PubMed

    Singh, Randhir; Kishore, Lalit; Kaur, Navpreet

    2014-02-01

    Diabetic neuropathy is a heterogeneous group of disorders with extremely complex pathophysiology and affects both somatic and autonomic components of the nervous system. Neuropathy is the most common chronic complication of diabetes mellitus. Metabolic disruptions in the peripheral nervous system, including altered protein kinase C activity, and increased polyol pathway activity in neurons and Schwann cells resulting from hyperglycemia plays a key role in the development of diabetic neuropathy. These pathways are related to the metabolic and/or redox state of the cell and are the major source of damage. Activation of these metabolic pathways leads to oxidative stress, which is a mediator of hyperglycemia induced cell injury and a unifying theme for all mechanisms of diabetic neuropathy. The therapeutic intervention of these metabolic pathways is capable of ameliorating diabetic neuropathy but therapeutics which target one particular mechanism may have a limited success. Available therapeutic approaches are based upon the agents that modulate pathogenetic mechanisms (glycemic control) and relieve the symptoms of diabetic neuropathy. This review emphasizes the pathogenesis, presently available therapeutic approaches and future directions for the management of diabetic neuropathy.

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

    PubMed

    Addington, James; Freimer, Miriam

    2016-01-01

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

  19. 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

  20. 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

  1. Painful peripheral neuropathy and sodium channel mutations.

    PubMed

    Hoeijmakers, Janneke G J; Faber, Catharina G; Merkies, Ingemar S J; Waxman, Stephen G

    2015-06-01

    Peripheral neuropathy can lead to neuropathic pain in a subset of patients. Painful peripheral neuropathy is a debilitating disorder, reflected by a reduced quality of life. Therapeutic strategies are limited and often disappointing, as in most cases targeted treatment is not available. Elucidating pathogenetic factors for pain might provide a target for optimal treatment. Voltage-gated sodium channels NaV1.7-NaV1.9 are expressed in the small-diameter dorsal root ganglion neurons and their axons. By a targeted gene approach, missense gain-of-function mutations of NaV1.7-NaV1.9 have been demonstrated in painful peripheral neuropathy. Functional analyses have shown that these mutations produce a spectrum of pro-excitatory changes in channel biophysics, with the shared outcome at the cellular level of dorsal root ganglion hyperexcitability. Reduced neurite outgrowth may be another consequence of sodium channel mutations, and possible therapeutic strategies include blockade of sodium channels or block of reverse operation of the sodium-calcium exchanger. Increased understanding of the pathophysiology of painful peripheral neuropathy offers new targets that may provide a basis for more effective treatment.

  2. Neuropathic pain in hereditary peripheral neuropathy

    PubMed Central

    Jeong, Na Young; Shin, Youn Ho; Jung, Junyang

    2013-01-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited motor and sensory neuropathy. Previous studies have shown that neuropathic pain is an occasional symptom of CMT referred by CMT patients. However, neuropathic pain is not considered a significant symptom in CMT patient and no researchers have studied profoundly the pathophysiology of neuropathic pain in CMT. Here, we highlight the relationship between CMT disease and neuropathic pain via previous several studies. PMID:24278891

  3. 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

  4. Diabetes, Peripheral Neuropathy, and Lower Extremity Function

    PubMed Central

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

    2014-01-01

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

  5. 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.

  6. 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.

  7. Validity of the neurological examination in diagnosing diabetic peripheral neuropathy.

    PubMed

    Höliner, Isabella; Haslinger, Vera; Lütschg, Jürg; Müller, Guido; Barbarini, Daniela Seick; Fussenegger, Jörg; Zanier, Ulrike; Saely, Christoph H; Drexel, Heinz; Simma, Burkhard

    2013-09-01

    The aim of this study was to evaluate the prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus and examine whether the neurological examination validly diagnoses diabetic peripheral neuropathy as compared with the gold standard of nerve conduction velocity in these patients. Nerve conduction velocity was measured in an unselected consecutive series of patients aged 8-18 years who had been suffering from type 1 diabetes mellitus for at least 1 year. For the neurological examination, neuropathy disability scores and neuropathy sign scores were used. Of the 39 patients, six (15%) had clinically evident diabetic peripheral neuropathy, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 15 (38%) patients. Sensitivity and specificity of the neurological examination for the diagnosis of diabetic peripheral neuropathy were 40% and 100%, respectively. The corresponding positive and negative predictive values were 100% and 72.7%, respectively. This conclusions from this study are that in children and adolescents with type 1 diabetes mellitus, diabetic peripheral neuropathy is highly prevalent, but in the majority of patients it is subclinical. Sensitivity and negative predictive values of the neurological examination are low. Therefore, routine nerve conduction velocity measurement for the assessment of diabetic peripheral neuropathy appears to be warranted in these patients.

  8. 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

  9. 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). |

  10. Tart Cherry Juice as a Treatment for Peripheral Neuropathy

    PubMed Central

    Carson, Cindy Alberts

    2015-01-01

    Introduction Tart cherries have a long history as a treatment for gout and joint pain. While the exact mechanism of action is unknown, it is believed that acanthocyanin pigments and related bioflavonoids found in tart cherries and other red fruits scavenge free radicals, modulate cytokines, reduce DNA degradation, decrease capillary permeability, inhibit cyclooxygenase, and strengthen biological membranes. Many of these biochemical reactions would be expected to reduce inflammation, pain, and edema. Significance of Study Peripheral polyneuropathies are common and are believed to affect up to 9% of the US population older than 50 y. These neuropathies may develop from direct compression of peripheral nerves, toxic or metabolic injury to nerve tissue, autoimmune attack, or nutritional deficiency. No cause is identified in approximately 30% of patients. The pathophysiology of polyneuropathies is complex and not fully understood, but 3 common patterns of damage occur: (1) distal axonopathy, where the cell bodies remain intact, but axons degenerate from distal to proximal, usually as the result of toxic or metabolic injury; (2) demyelination neuropathy, where damage to the myelin sheath from autoimmune, infectious, or other causes disrupts electrical signaling; and (3) ganglionopathies, where damage occurs at the cell body or neuron, a relatively rare occurrence. While weakness and loss of sensation are common in many peripheral polyneuropathies, “gain of function” symptoms, such as paresthesias and allodynia, are the most distressing and are very difficult to treat. It is believed that these symptoms are caused by alterations in ion channels, alterations in neurotransmitters and their receptors, and altered gene expression. Common conventional treatments include antiepileptics, antidepressants, NSAIDs, and narcotics. These medications alter ion channels and neurotransmitters, decrease the sensitivity of nociceptive receptors, and desensitize C fibers. Most patients

  11. Performance-based physical functioning and peripheral neuropathy in a population-based cohort of women at midlife.

    PubMed

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

    2013-04-15

    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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Arsenic intoxication presenting with macrocytosis and peripheral neuropathy, without anemia.

    PubMed

    Heaven, R; Duncan, M; Vukelja, S J

    1994-01-01

    A case of arsenic intoxication associated with macrocytosis and neuropathy, without anemia, is presented. Evaluation of a 68-year-old man with a long history of peripheral neuropathy and persistent macrocytosis revealed exposure to an insecticide. Analysis of urine and hair revealed elevated levels of arsenic. A short course of d-penicillamine failed to promote urinary excretion of arsenic. Removal of the insecticide resulted in resolution of macrocytosis and slight improvement of neuropathy. This case emphasizes that arsenic intoxication should be considered in patients with macrocytosis with peripheral neuropathy, even in the absence of anemia.

  19. 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

  20. 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

  1. African Mitochondrial DNA Subhaplogroups and Peripheral Neuropathy during Antiretroviral Therapy

    PubMed Central

    Canter, Jeffrey A.; Robbins, Gregory K.; Selph, Doug; Clifford, David B.; Kallianpur, Asha R.; Shafer, Robert; Levy, Shawn; Murdock, Deborah G.; Ritchie, Marylyn D.; Haas, David W.; Hulgan, Todd

    2010-01-01

    Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs) was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine if NRTI-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic blacks with genomic data, 51 (33%) developed peripheral neuropathy. In a multivariate model, African mtDNA subhaplogroup L1c was an independent predictor of peripheral neuropathy (OR=3.7, 95% CI 1.1-12.0). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to NRTI-associated toxicity. PMID:20402593

  2. 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

  3. Intravenous immunoglobulins in peripheral neuropathy associated with vasculitis

    PubMed Central

    Levy, Y; Uziel, Y; Zandman, G; Amital, H; Sherer, Y; Langevitz, P; Goldman, B; Shoenfeld, Y

    2003-01-01

    Objective: To present patients who exhibited various inflammatory diseases accompanied with vasculitic peripheral neuropathies for which intravenous immunoglobulin (IVIg) was used for treatment. Methods: Six patients with Sjögren's syndrome, systemic lupus erythematosus (SLE), vaccination induced vasculitis, Churg-Strauss vasculitis, mixed cryoglobulinaemia associated with hepatitis C infection, or sarcoidosis were included. All developed vasculitic peripheral neuropathy, and were treated with high dose IVIg (2 g/kg body weight). The patients were followed up for 1–5 years after this treatment. Results: In four patients (Sjögren's syndrome, Churg-Strauss vasculitis, SLE, and vaccination induced vasculitis) the neuropathy resolved after IVIg treatment. Conclusion: IVIg may be beneficial in cases of resistant vasculitic peripheral neuropathy. IVIg should probably be considered as a sole or adjuvant treatment for patients with contraindications to conventional treatment, or alternatively, for patients in whom conventional treatment has failed. PMID:14644864

  4. Chronic peripheral neuropathy responsive to rituximab.

    PubMed

    Kelly, John J

    2006-01-01

    A 73-year-old man was referred for evaluation of unsteady gait and numbness of the feet. His symptoms had progressed over the previous 3 years from numbness and tingling in his left lateral thigh to a gait imbalance severe enough to necessitate crutches for ambulation. After a thorough neurological work-up, including an electromyogram that was markedly abnormal, and extensive testing for anti-nerve antibodies, a diagnosis of neuropathy, secondary to monoclonal IgM antibodies against myelin-associated glycoprotein, was made. Aggressive treatment was deemed necessary; however, none of the standard options, including intravenous immunoglobulin, prednisone, and cytotoxic drugs, seemed suitable given his underlying health and the severity of his deficit. A course of rituximab 375 mg/m2 weekly for 4 weeks was recommended for the patient. Shortly after the treatment was completed, he began to notice a slow and steady improvement. Within 3 months his gait had improved to the point where he no longer required crutches or a cane and he was able to return to work.

  5. [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.

  6. [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

  7. Sodium Channels, Mitochondria, and Axonal Degeneration in Peripheral Neuropathy.

    PubMed

    Persson, Anna-Karin; Hoeijmakers, Janneke G J; Estacion, Mark; Black, Joel A; Waxman, Stephen G

    2016-05-01

    Peripheral neuropathy results from damage to peripheral nerves and is often accompanied by pain in affected limbs. Treatment represents an unmet medical need and a thorough understanding of the mechanisms underlying axonal injury is needed. Longer nerve fibers tend to degenerate first (length-dependence), and patients carrying pathogenic mutations throughout life usually become symptomatic in mid- or late-life (time-dependence). The activity of voltage-gated sodium channels can contribute to axonal injury and sodium channel gain-of-function mutations have been linked to peripheral neuropathy. Recent studies have implicated sodium channel activity, mitochondrial compromise, and reverse-mode Na(+)/Ca(2+) exchange in time- and length-dependent axonal injury. Elucidation of molecular mechanisms underlying axonal injury in peripheral neuropathy may provide new therapeutic strategies for this painful and debilitating condition.

  8. Evaluation of peripheral neuropathy. Part III: vasculitic, infectious, inherited, and idiopathic neuropathies.

    PubMed

    Kelly, John J

    2005-01-01

    In this, the third of a 3-part series on peripheral neuropathy, the syndromes of vasculitic, infectious, inherited, and idiopathic neuropathy are discussed. Vasculitis is a frequent cause of neuropathy in the setting of a connective tissue disease. The infectious neuropathies most likely to be encountered in the United States are those due to varicella-zoster virus, human immunodeficiency virus, Lyme disease, hepatitis C virus, and, most recently, West Nile virus. Inherited neuropathies are divided into 2 main types: predominant motor or predominant sensory. The former are generally classed as the Charcot-Marie-Tooth diseases and the latter as the hereditary sensory neuropathies. Each category has a number of different subtypes. If the results of routine screening tests are negative, the clinician must consider special testing for unusual disorders, including evaluations for underlying autoimmune or malignant disorders, genetic tests for inherited neuropathies, and other unusual or selectively ordered tests. These tests are very expensive and should be ordered only after the common causes of neuropathy are excluded. Unless the neuropathy can be substantially alleviated or cured, symptomatic treatment (most often for pain) plays a significant role for these patients.

  9. 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

  10. 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

  11. Severe peripheral neuropathy after exposure to monosodium methyl arsonate.

    PubMed

    Hessl, S M; Berman, E

    1982-05-01

    A case of severe peripheral neuropathy after several days of exposure to a pesticide spray containing monosodium methyl arsonate (MSMA) is reported. The clinical manifestations of symmetrical peripheral neuropathy with stocking-glove sensory deficit, decreased position sense, decreased and absent deep tendon reflexes, and muscle wasting are consistent with those described in other cases of arsenic intoxication. The anemia, leukopenia, and bone marrow changes of dyserythropoiesis in this case are also similar to those previously described with arsenic intoxication. The authors discuss the possible contribution of toxicity from exposure to other pesticides.

  12. A clinical decision support system with an integrated EMR for diagnosis of peripheral neuropathy.

    PubMed

    Kunhimangalam, Reeda; Ovallath, Sujith; Joseph, Paul K

    2014-04-01

    The prevalence of peripheral neuropathy in general population is ever increasing. The diagnosis and classification of peripheral neuropathies is often difficult as it involves careful clinical and electro-diagnostic examination by an expert neurologist. In developing countries a large percentage of the disease remains undiagnosed due to lack of adequate number of experts. In this study a novel clinical decision support system has been developed using a fuzzy expert system. The study was done to provide a solution to the demand of systems that can improve health care by accurate diagnosis in limited time, in the absence of specialists. It employs a graphical user interface and a fuzzy logic controller with rule viewer for identification of the type of peripheral neuropathy. An integrated medical records database is also developed for the storage and retrieval of the data. The system consists of 24 input fields, which includes the clinical values of the diagnostic test and the clinical symptoms. The output field is the disease diagnosis, whether it is Motor (Demyelinating/Axonopathy) neuropathy, sensory (Demyelinating/Axonopathy) neuropathy, mixed type or a normal case. The results obtained were compared with the expert's opinion and the system showed 93.27 % accuracy. The study aims at showing that Fuzzy Expert Systems may prove useful in providing diagnostic and predictive medical opinions. It enables the clinicians to arrive at a better diagnosis as it keeps the expert knowledge in an intelligent system to be used efficiently and effectively.

  13. Significant response to lacosamide in a patient with severe chemotherapy-induced peripheral neuropathy.

    PubMed

    Ibrahim, Samar A; Albany, Zhanna; Albany, Constantine

    2015-05-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity of potentially curative cancer therapy regimens. Cisplatin is the class of chemotherapy agent that has a broad spectrum of activity against several solid tumors, but it induces sensory neuropathy of upper and lower extremities. Cisplatin-induced peripheral neuropathy is usually in a "gloves and socks" distribution that can persist for months or years after completion of chemotherapy treatment. If the pain is severe, it affects the patient's long-term quality of life and can potentially result in chemotherapy dose reduction or treatment discontinuation. The mechanism of CIPN is not well understood, and a number of pathophysiological mechanisms have been proposed to explain the phenomenon. Although many therapies have been investigated for the prevention or treatment of CIPN, there is currently no accepted proven therapy. Here we report a case in which lacosamide alleviated painful CIPN symptoms. Lacosamide is an anticonvulsant drug that blocks the voltage-gated sodium channels in the neurons and may also be a promising novel candidate for the prevention and treatment of chemotherapy-induced peripheral neuropathy. Preclinical data support the role of lacosamide protective effect in a rat model of chemotherapy-induced neuropathy, randomized clinical trial is needed.

  14. An early diagnostic tool for diabetic peripheral neuropathy in rats.

    PubMed

    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.

  15. 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

  16. 77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... for Peripheral Neuropathy; Public Workshop; Request for Comments AGENCY: Food and Drug Administration...-modifying agents for the treatment of peripheral neuropathy. Discussion will focus on possible therapeutic targets for these agents, the types of painful peripheral neuropathies amenable to treatment with...

  17. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases.

    PubMed

    Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin

    2014-07-15

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

  18. 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.

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

    PubMed

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

    2016-04-01

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

  20. Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms

    PubMed Central

    Ferrari, Luiz F.; Levine, Jon D.

    2010-01-01

    A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC) (50 mg/kg) neuropathy was mitochondrial dependent and PKCε independent, and alcohol-induced painful neuropathy, PKCε dependent and mitochondrial independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for one week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial dependent but PKCε independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction. PMID:20726883

  1. CD31(+) cell transplantation promotes recovery from peripheral neuropathy.

    PubMed

    Li, YongNan; Zhang, ZhuoBo; Kim, Han-Soo; Han, Seongho; Kim, Sung-Whan

    2014-09-01

    Recently, we reported that human peripheral blood (PB)-derived CD31(+) cells are highly angiogenic. In this study, we investigated the beneficial effects of CD31(+) cells on peripheral neuropathy in mice. CD31(+) cells were collected from the peripheral blood using magnetic activated cell sorting. CD31(+) cells exhibited higher levels of expression of angiogenic genes on real-time reverse transcriptase polymerase chain reaction. Peripheral neuropathy was induced by crushing the sciatic nerve with a hemostat, and CD31(+) cells were then injected intramuscularly along the sciatic nerve. CD31(+) cell transplantation restored motor nerve conduction velocity and voltage amplitude and improved motor coordination. In addition, CD31(+) cell transplantation significantly improved blood perfusion and increased intraneural vascularity in the sciatic nerve. Whole-mount fluorescent imaging and dot blot analysis showed that CD31(+) cells in the nerve possessed high engraftment and anti-apoptotic properties. Additionally, injected CD31(+) cells displayed neurovascular tropism and are highly incorporated with vasculature. Angiogenic cytokines were augmented in CD31(+)-injected nerve tissue, suggesting increased neovascularization. Taken together, these results indicate that CD31(+) cells might be a novel therapeutic strategy in the treatment of peripheral neuropathy. PMID:25128805

  2. [Arsenous anhydride poisoning. Peripheral neuropathy and changes in cognitive functions].

    PubMed

    Danan, M; Conso, F; Dally, S; Bertaux, L; Chouraki, L; Balme, R

    1985-01-01

    The authors report the evolution over an 11 months period of a case of subacute intoxication with arsenic in a 30 years old woman. In addition to the classical peripheral neuropathy, we observed impairment of the superior neurological functions which improved together with the neuropathy. These malfunctions are rarely described in the literature although arsenic seems to cross the blood-brain barrier easily. There is no other explanation, and we believe arsenic to be responsible for these disturbances. We suggest systematic testing of the superior neurological functions in cases of arsenic intoxication.

  3. Peripheral neuropathy in lead-intoxicated sickle cell patients.

    PubMed

    Imbus, C E; Warner, J; Smith, E; Pegelow, C H; Allen, J P; Powars, D R

    1978-01-01

    Peripheral neuropathy and hypertension caused by lead intoxication are reported in two children with sickle cell anemia. One child had generalized weakness in the initial occurrence and distal paralysis during a relapse two years later. The second child had foot and wrist drop. Both had slow peripheral nerve conduction velocities during the episodes. Chelation therapy was successful and resulted in a return of strength (over a period of several months) and a normalization of the blood pressures. Children with sickle cell anemia who are subjected to lead intoxication appear to be predisposed to peripheral nerve damage.

  4. 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

  5. Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment.

    PubMed

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

    2012-11-01

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

  6. 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

  7. Insidious peripheral neuropathy occurring under treatment in infantile MTHFR deficiency.

    PubMed

    Chaabene-Masmoudi, A; Mesrati, F; Zittoun, J; Landrieu, P

    2009-12-01

    5,10-Methylenetetrahydrofolate reductase (MTHFR) deficiency was diagnosed in a 1-month-old baby with signs of cerebral distress. Under a classic treatment using methionine supplementation, methyl donor (betaine) folinic acid, vitamin B(6) and vitamin B(12), the neuromotor development was satisfactory. At 15 years of age, however, despite no clear modification of the biochemical markers in body fluids, she developed a clinically overt peripheral axonal neuropathy. Only partial clinical improvement was obtained after reinforcement of betaine doses. Surveillance of the peripheral nerve is indicated in MTHFR deficiency, including in the infantile form with a good therapeutic compliance.

  8. 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.

  9. Angiogenin gene polymorphism: A risk factor for diabetic peripheral neuropathy in the northern Chinese Han population.

    PubMed

    Wang, Hongli; Fan, Dongsheng; Zhang, Yingshuang

    2013-12-25

    Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mellitus (129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy patients) and 268 healthy controls. All subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistically significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.

  10. Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis

    PubMed Central

    Brock, Christina; Søfteland, Eirik; Gunterberg, Veronica; Frøkjær, Jens Brøndum; Lelic, Dina; Brock, Birgitte; Dimcevski, Georg; Gregersen, Hans; Simrén, Magnus; Drewes, Asbjørn Mohr

    2013-01-01

    OBJECTIVE Long-term diabetes leads to severe peripheral, autonomous, and central neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut axis thus expresses a neurophysiological profile, and heart rate variability (HRV) can be correlated with clinical gastrointestinal symptoms. RESEARCH DESIGN AND METHODS Fifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (SF-36 Short Form Survey) were collected. RESULTS Diabetic patients had autonomous neuropathy, evidenced by decreased electrocardiographic R-R interval (P = 0.03) and lower HRV (P = 0.008). Patients were less sensitive to painful stimulation (P = 0.007), had prolonged latencies of evoked potentials (P ≤ 0.001), and showed diminished amplitude of the N2–P2 component in evoked potentials (P = 0.01). There was a caudoanterior shift of the insular brain source (P = 0.01) and an anterior shift of the cingulate generator (P = 0.01). Insular source location was associated with HRV assessments (all P < 0.02), and the shift (expressed in mm) correlated negatively with physical health (P < 0.001) and positively with nausea (P = 0.03) and postprandial fullness (P = 0.03). Cingulate source shift was correlated negatively with physical health (P = 0.005) and positively with postprandial fullness (P ≤ 0.001). CONCLUSIONS This study provides evidence for interaction between autonomic neuropathy and peripheral nervous degeneration, as well as changes in dipole sources in diabetic patients with gastrointestinal symptoms. The findings may lead to improved

  11. Peripheral neuropathies associated with monoclonal gammopathies of undetermined significance.

    PubMed

    Kelly, John J

    2008-01-01

    Monoclonal gammopathies (MGs) or plasma cell dyscrasias (PCDs) are hematologic disorders that may affect peripheral nerves. An MG is a proliferation of a single clone of neoplastic or nonneoplastic plasma that usually secretes a monoclonal protein (M-protein) serum or urine. If a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) is established, a sudden increase in M-protein levels can indicate malignant transformation of a benign PCD. Roughly 50% of MGUS neuropathies are associated with an IgM gammopathy and the remaining 50% with IgG- and IgA-MGUS-associated neuropathies. MGUS is the most common of the PCDs associated with neurologic disorders, which are easily approached clinically by classifying them as IgM or non-IgM types.

  12. Lead-induced peripheral neuropathy following Ayurvedic medication.

    PubMed

    Singh, Surjit; Mukherjee, K K; Gill, K D; Flora, S J S

    2009-09-01

    Lead poisoning following intake of Ayurvedic medication is one of the recent areas of concern. We report a case of a 58-year-old type II diabetic man who was stable with diet control and 30 mg pioglitazone per day. He took Ayurvedic medication for generalized weakness and developed peripheral neuropathy following its intake. He was found to have high blood and urinary lead levels and was diagnosed to have subacute lead poisoning. He was treated with d-Penicillamine for 8 weeks, following which his lead levels became normal. The use of d-Penicillamine was proved highly effective in treating a case of lead poisoning. PMID:19805920

  13. 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

  14. 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.

  15. The evaluation of peripheral neuropathy. Part II: Identifying common clinical syndromes.

    PubMed

    Kelly, John J

    2004-01-01

    The first of this 3-part series on the diagnosis and management of peripheral neuropathy focused on the recognition of neuropathy and its clinical and laboratory characterization as essential to determining etiology. This approach allows for the construction of a differential diagnosis that can be narrowed by subsequent diagnostic testing. This installment, along with the final one, will focus on recognition and management of common neuropathies likely to be seen by the average practitioner. Neuropathies covered in this second part include diabetic, autoimmune and inflammatory, toxic, neuropathies associated with plasma cell dyscrasias, and paraneoplastic neuropathies.

  16. 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

  17. 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

  18. Diabetic autonomic neuropathy.

    PubMed

    Freeman, Roy

    2014-01-01

    Diabetes mellitus is the commonest cause of an autonomic neuropathy in the developed world. Diabetic autonomic neuropathy causes a constellation of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. Several discrete syndromes associated with diabetes cause autonomic dysfunction. The most prevalent of these are: generalized diabetic autonomic neuropathy, autonomic neuropathy associated with the prediabetic state, treatment-induced painful and autonomic neuropathy, and transient hypoglycemia-associated autonomic neuropathy. These autonomic manifestations of diabetes are responsible for the most troublesome and disabling features of diabetic peripheral neuropathy and result in a significant proportion of the mortality and morbidity associated with the disease.

  19. 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

  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. Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats.

    PubMed

    Yamamoto, Shota; Kawashiri, Takehiro; Higuchi, Hitomi; Tsutsumi, Kuniaki; Ushio, Soichiro; Kaname, Takanori; Shirahama, Masafumi; Egashira, Nobuaki

    2015-09-01

    Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN), because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg), pregabalin (3 mg/kg), duloxetine (30 mg/kg) or mexiletine (100 mg/kg), but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy. PMID:26362518

  2. Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats.

    PubMed

    Yamamoto, Shota; Kawashiri, Takehiro; Higuchi, Hitomi; Tsutsumi, Kuniaki; Ushio, Soichiro; Kaname, Takanori; Shirahama, Masafumi; Egashira, Nobuaki

    2015-09-01

    Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN), because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg), pregabalin (3 mg/kg), duloxetine (30 mg/kg) or mexiletine (100 mg/kg), but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy.

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2016-07-01

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

  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. 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.

  7. Painful Diabetic Peripheral Neuropathy: Presentations, Mechanisms, and Exercise Therapy

    PubMed Central

    Yoo, Min; Sharma, Neena; Pasnoor, Mamatha; Kluding, Patricia M

    2013-01-01

    Diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes and a major cause of morbidity and increased mortality. It is typically characterized by significant deficits in tactile sensitivity, vibration sense, lower-limb proprioception, and kinesthesia. Painful diabetic neuropathy (P-DPN) is a common phenotype of DPN that affects up to one-third of the general diabetic population. P-DPN has been shown to be associated with significant reductions in overall quality of life, increased levels of anxiety and depression, sleep impairment, and greater gait variability. The purpose of this review is to examine proposed mechanisms of P-DPN, summarize current treatment regimen, and assess exercise as a potential therapy for P-PDN. Although exercise has been shown to be an effective therapeutic modality for diabetes, its specific effects on DPN and especially the painful phenotype have not been sufficiently investigated in current literature. Several rodent models and clinical trials have presented promising results in this area, and warrant further investigations examining the effect of exercise on P-DPN. PMID:25360348

  8. Painful Diabetic Peripheral Neuropathy: Presentations, Mechanisms, and Exercise Therapy.

    PubMed

    Yoo, Min; Sharma, Neena; Pasnoor, Mamatha; Kluding, Patricia M

    2013-06-30

    Diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes and a major cause of morbidity and increased mortality. It is typically characterized by significant deficits in tactile sensitivity, vibration sense, lower-limb proprioception, and kinesthesia. Painful diabetic neuropathy (P-DPN) is a common phenotype of DPN that affects up to one-third of the general diabetic population. P-DPN has been shown to be associated with significant reductions in overall quality of life, increased levels of anxiety and depression, sleep impairment, and greater gait variability. The purpose of this review is to examine proposed mechanisms of P-DPN, summarize current treatment regimen, and assess exercise as a potential therapy for P-PDN. Although exercise has been shown to be an effective therapeutic modality for diabetes, its specific effects on DPN and especially the painful phenotype have not been sufficiently investigated in current literature. Several rodent models and clinical trials have presented promising results in this area, and warrant further investigations examining the effect of exercise on P-DPN.

  9. 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

  10. 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

  11. Autosomal recessive spinocerebellar ataxia and peripheral neuropathy with raised alpha-fetoprotein.

    PubMed

    Izatt, Louise; Németh, Andrea H; Meesaq, Anjela; Mills, Kerry R; Taylor, A Malcolm R; Shaw, Christopher E

    2004-07-01

    We describe three patients from two families with progressive spinocerebellar ataxia, peripheral neuropathy, raised alpha-fetoprotein (AFP) and hypercholesterolaemia. Two siblings had identical clinical features, with late childhood onset of symptoms and slow progression, requiring crutches to walk at ages 37 and 38 years. Another patient developed ataxia aged 13 years and became wheel-chair bound by 20 years of age. Although they all had raised serum AFP levels, their clinical, immunological, biochemical, cytogenetic and molecular genetic studies failed to support a diagnosis of Ataxia Telangiectasia. Extensive investigation including imaging, biochemical and genetic studies excluded other known ataxias. Their clinical features most closely resemble the phenotype of a single consanguineous Japanese family with four individuals affected by spinocerebellar ataxia, peripheral neuropathy, raised AFP and hypercholesterolaemia. Homozygosity mapping has identified a locus in this Japanese family at 9q34. Haplotype analysis of our cases demonstrated possible linkage to 9q34, suggesting these may be the first Caucasian families described with this disorder.

  12. 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

  13. Pilot Study of Exercise Therapy on Painful Diabetic Peripheral Neuropathy

    PubMed Central

    Yoo, Min; D’Silva, Linda; Martin, Katherine; Sharma, Neena; Pasnoor, Mamatha; LeMaster, Joseph

    2015-01-01

    Objective Painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes. While the beneficial effect of exercise on diabetes is well established, its effect specifically on painful DPN has not been thoroughly explored. The objective of this pilot study was to examine the effect of aerobic exercise on pain in people with DPN. Methods Fourteen sedentary individuals (mean age 57±5.11 years) with painful DPN were enrolled in a 16-week, supervised aerobic exercise program. The Brief Pain Inventory-Diabetic Peripheral Neuropathy (BPI-DPN) was used to assess pain intensity (worst, least, average, now) and pain interference with daily life (activity, mood, walk, normal work, relationship, sleep, enjoyment of life) pre- and post -intervention. Body mass index (BMI), maximum oxygen uptake (VO2max), hemoglobin A1c (HbA1c), and blood pressure were also measured pre-and post-intervention as secondary outcomes of interest. Results Significant reductions in pain interference were observed with walking (4.93±3.03 pre to 3.29±2.89 post, p=0.016), normal work (5.39±3.32 pre to 3.79±3.04 post, p=0.032), relationship with others (3.96±3.53 pre to 1.29±1.27 post, p=0.006), sleep (5.11±3.04 pre to 3.5±3.03 post, p=0.02), and the overall pain interference (4.65±2.70 pre to 2.97±2.22 post, p=0.013) following the intervention; however, there was no change in pain intensity. VO2max increased significantly post-intervention (16.02±3.84ml/kg/min pre to 17.18±4.19ml/kg/min, p=0.028), while BMI, HbA1c, and blood pressure remained unchanged. Conclusion These preliminary results suggest that perceived pain interference may be reduced following an aerobic exercise intervention among people with painful DPN, without a change in pain intensity. Further validation by a RCT is needed. PMID:25800666

  14. Chemotherapy-induced peripheral neuropathy: What do we know about mechanisms?

    PubMed

    Carozzi, V A; Canta, A; Chiorazzi, A

    2015-06-01

    Cisplatin, oxaliplatin, paclitaxel, vincristine and bortezomib are some of the most effective drugs successfully employed (alone or in combinations) as first-line treatment for common cancers. However they often caused severe peripheral neurotoxicity and neuropathic pain. Structural deficits in Dorsal Root Ganglia and sensory nerves caused symptoms as sensory loss, paresthesia, dysaesthesia and numbness that result in patient' suffering and also limit the life-saving therapy. Several scientists have explored the various mechanisms involved in the onset of chemotherapy-related peripheral neurotoxicity identifying molecular targets useful for the development of selected neuroprotective strategies. Dorsal Root Ganglia sensory neurons, satellite cells, Schwann cells, as well as neuronal and glial cells in the spinal cord, are the preferential sites in which chemotherapy neurotoxicity occurs. DNA damage, alterations in cellular system repairs, mitochondria changes, increased intracellular reactive oxygen species, alterations in ion channels, glutamate signalling, MAP-kinases and nociceptors ectopic activation are among the events that trigger the onset of peripheral neurotoxicity and neuropathic pain. In the present work we review the role of the main players in determining the pathogenesis of anticancer drugs-induced peripheral neuropathy.

  15. 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.

  16. National Cancer Institute-supported chemotherapy-induced peripheral neuropathy trials: outcomes and lessons

    PubMed Central

    Majithia, Neil; Temkin, Sarah M.; Ruddy, Kathryn J.; Beutler, Andreas S.; Hershman, Dawn L.; Loprinzi, Charles L.

    2016-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and debilitating complications of cancer treatment. Due to a lack of effective management options for patients with CIPN, the National Cancer Institute (NCI) sponsored a series of trials aimed at both prevention and treatment. A total of 15 such studies were approved, evaluating use of various neuro-modulatory agents which have shown benefit in other neuropathic pain states. Aside from duloxetine, none of the pharmacologic methods demonstrated therapeutic benefit for patients with CIPN. Despite these disappointing results, the series of trials revealed important lessons that have informed subsequent work. Some examples of this include the use of patient-reported symptom metrics, the elimination of traditional—yet unsubstantiated—practice approaches, and the discovery of molecular genetic predictors of neuropathy. Current inquiry is being guided by the results from these large-scale trials, and as such, stands better chance of identifying durable solutions for this treatment-limiting toxicity. PMID:26686859

  17. 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

  18. 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

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

    PubMed

    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

    2014-09-01

    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 (7day 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

  20. Dorsal Root Ganglia Sensory Neuronal Cultures: a tool for drug discovery for peripheral neuropathies

    PubMed Central

    Melli, Giorgia; Höke, Ahmet

    2010-01-01

    Background Peripheral neuropathies affect many people worldwide and are caused by or associated with a wide range of conditions, both genetic and acquired. Current therapies are directed at symptomatic control because no effective regenerative treatment exists. Primary challenge is that mechanisms that lead to distal axonal degeneration, a common feature of all peripheral neuropathies, are largely unknown. Objective/Methods To address the role and specific characteristics of dorsal root ganglia (DRG) derived sensory neuron culture system as a useful model in evaluating the pathogenic mechanisms of peripheral neuropathies and examination and validation of potential therapeutic compounds. A thorough review of the recent literature was completed and select examples of the use of DRG neurons in different peripheral neuropathy models were chosen to highlight the utility of these cultures. Conclusion Many useful models of different peripheral neuropathies have been developed using DRG neuronal culture and potential therapeutic targets have been examined, but so far none of the potential therapeutic compounds have succeeded in clinical trials. In recent years, focus has changed to evaluation of axon degeneration as the primary outcome measure advocating a drug development strategy starting with phenotypic drug screening, followed by validation in primary complex co-cultures and animal models. PMID:20657751

  1. The long-term impact of oxaliplatin chemotherapy on rodent cognition and peripheral neuropathy.

    PubMed

    Fardell, Joanna E; Vardy, Janette; Monds, Lauren A; Johnston, Ian N

    2015-09-15

    Chemotherapy treatment is associated with cognitive dysfunction in cancer survivors after treatment completion. The duration of these impairments is unclear. Therefore this paper aims to evaluate the lasting impact of varying doses of the chemotherapy oxaliplatin (OX) on cognition and peripheral neuropathy. In Experiment 1 rats were treated once a week for 3 weeks with either physiological saline (control) or 6 mg/kg OX i.p. and were assessed for peripheral neuropathy, using von Frey filaments, and cognitive function, using novel object and location recognition, up to 2 weeks after treatment completion. For Experiment 2 rats received 3 weekly i.p. injections of either physiological saline (control), 0.6 mg/kg, 2mg/kg or 6 mg/kg OX and assessed for peripheral neuropathy and cognitive function up to 11 months after treatment completion. Systemic OX treatment induced lasting effects on cognitive function at 11 months after treatment, and peripheral neuropathy at 1 month after treatment and these were dose dependent; higher doses of OX resulted in worse cognitive outcomes and more severe peripheral neuropathy.

  2. 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. ...

  3. Clinical value of tapentadol extended-release in painful diabetic peripheral neuropathy.

    PubMed

    Desai, Bansri; Freeman, Erin; Huang, Ellen; Hung, Anna; Knapp, Edward; Breunig, Ian M; McPherson, Mary L; Shaya, Fadia T

    2014-03-01

    Painful diabetic peripheral neuropathy is difficult to treat, partially because the underlying mechanism of pain is not fully understood. Various treatment guidelines recommend first-line agents, such as α2-δ ligands, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants but combination therapy of alternative agents including opiates is often warranted. Tapentadol extended-release has a novel dual mechanism of action; it is both a mu-opioid receptor agonist and a norephinephrine reuptake inhibitor. It has been in the spotlight since it was FDA-approved specifically for the treatment of painful diabetic peripheral neuropathy in 2012. Previous reviews of tapentadol have focused on chronic pain. The purpose of this review article is to assess the efficacy and safety of tapentadol extended-release in adult populations with painful diabetic peripheral neuropathy and provide guidance for formulary decisions. PMID:24524594

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

    PubMed

    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.

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

    PubMed

    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

  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. 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

  8. Elevated neurofilament light chain (NFL) mRNA levels in prediabetic peripheral neuropathy.

    PubMed

    Celikbilek, Asuman; Tanik, Nermin; Sabah, Seda; Borekci, Elif; Akyol, Lutfi; Ak, Hakan; Adam, Mehmet; Suher, Murat; Yilmaz, Neziha

    2014-06-01

    Evidence suggests that peripheral nerve injury occurs during the early stages of disease with mild glycemic dysregulation. Two proteins, neuron-specific enolase (NSE) and neurofilament light chain (NFL), have been examined previously as possible markers of neuronal damage in the pathophysiology of neuropathies. Herein, we aimed to determine the potential value of circulatory NSE and NFL mRNA levels in prediabetic patients and in those with peripheral neuropathy. This prospective clinical study included 45 prediabetic patients and 30 age- and sex-matched controls. All prediabetic patients were assessed with respect to diabetes-related microvascular complications, such as peripheral neuropathy, retinopathy and nephropathy. mRNA levels of NSE and NFL were determined in the blood by real-time polymerase chain reaction. NSE mRNA levels were similar between prediabetic and control groups (p > 0.05), whereas NFL mRNA levels were significantly higher in prediabetics than in controls (p < 0.001). NSE mRNA levels did not significantly differ between prediabetic patients with and without peripheral neuropathy (p > 0.05), while NFL mRNA levels were significantly higher in prediabetics with peripheral neuropathy than in those without (p = 0.038). According to correlation analysis, NFL mRNA levels were positively correlated with the Douleur Neuropathique 4 questionnaire score in prediabetic patients (r = 0.302, p = 0.044). This is the first study to suggest blood NFL mRNA as a surrogate marker for early prediction of prediabetic peripheral neuropathy, while NSE mRNA levels may be of no diagnostic value in prediabetic patients.

  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. Treatment of multiple myeloma: thalidomide-, bortezomib-, and lenalidomide-induced peripheral neuropathy.

    PubMed

    Koeppen, Susanne

    2014-01-01

    Over the last 15 years, substantial progress has been made in the treatment of patients with multiple myeloma (MM). New chemotherapeutic options with the immunomodulatory drugs thalidomide and lenalidomide and with the proteasome inhibitor bortezomib have increased the response rates before and after autologous hematopoietic stem cell transplantation (ASCT). Incorporation of the novel agents into the treatment of newly diagnosed MM and at relapse is now standard of care also for patients with MM not eligible for ASCT. However, the use of thalidomide and bortezomib is frequently associated with a dose-limiting peripheral neuropathy. In order to take full advantage of the therapeutic potential, a risk assessment for neurotoxicity is needed on a case-by-case basis. This assessment includes pre-existing neurological symptoms due to the MM, any comorbidities, and past or planned treatment regimens. The aim is to achieve maximum efficacy while minimizing the risk of developing chemotherapy-induced polyneuropathy (CIPN). This requires a neurological evaluation of the patient at regular intervals, the implementation of preventive measures, and the development of validated therapeutic strategies for emerging neurotoxic side effects. This review focuses on the incidence, prevention, and management of peripheral neurotoxicity due to thalidomide, bortezomib, and lenalidomide in the treatment of MM.

  11. Molecular genetics and biology of inherited peripheral neuropathies: a fast-moving field.

    PubMed

    Nelis, E; Timmerman, V; De Jonghe, P; Van Broeckhoven, C; Rautenstrauss, B

    1999-09-01

    The recent progress of molecular genetics has considerably increased our knowledge about the underlying disease mechanism of inherited peripheral neuropathies. Mutations in three genes coding for the myelin proteins peripheral myelin protein 22, myelin protein zero and connexin 32 and in one gene coding for the transcription factor early growth response 2 element are associated with Charcot-Marie-Tooth type 1 and 2, hereditary neuropathy with liability to pressure palsies, Dejerine-Sottas syndrome and congenital hypomyelination. This review focuses on the correlation of the different human phenotypes associated with distinct mutations with those found in cellular and animal models. PMID:10541586

  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. 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

  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.

  15. 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...

  16. 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.

  17. 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

  18. [Peripheral neuropathies in the State of São Paulo from 1939 to 1985].

    PubMed

    Barreira, A A; Marques Júnior, W

    1997-03-01

    Studies on peripheral neuropathies by investigators residing in the State of São Paulo, Brazil, and published since the 1930 and 1940 decades until 1985 were revised in the present survey. Investigations in the area were greatly encouraged by the appearance of the journal Arquivos de Neuro-Psiquiatria(São Paulo). Oswaldo Freitas Julião may be considered the author who began these studies in the State and his most important contributions were related to leprosy and to Andrade disease, although he also published papers on other types of peripheral neuropathies. Horacio Martins Canelas also made a very important contribution to the study of different neuropathies, especially those due to vitamin B12 deficiency. A series of papers on neuropathies published by neurologists residing in the State is summarized. We also present a catalogue of the major university centers where groups of neurologists preferentially devote their time to the study of neuromuscular disease in São Paulo and a selected bibliography about neuropathies by investigators from this State.

  19. 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.

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

    PubMed

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

    2016-03-01

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

  1. 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

  2. [Diabetic neuropathy].

    PubMed

    Lechleitner, Monika; Abrahamian, Heidemarie; Francesconi, Claudia; Kofler, Markus

    2016-04-01

    These are the guidelines for diagnosis and treatment of diabetic neuropathy. This diabetic late complication comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy. The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided.

  3. The effect of mindfulness meditation on painful diabetic peripheral neuropathy in adults older than 50 years.

    PubMed

    Teixeira, Elizabeth

    2010-01-01

    This pilot study explored the effect of mindfulness meditation for diabetic neuropathy. Twenty participants (10 in each group) completed the study. No significant differences were found between the groups. However, differences between the means were found on 2 constructs: pain quality of life and symptom-related quality of life. Further studies may show efficacy.

  4. 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

  5. Similar pattern of peripheral neuropathy in mouse models of type 1 diabetes and Alzheimer's disease.

    PubMed

    Jolivalt, C G; Calcutt, N A; Masliah, E

    2012-01-27

    There is an increasing awareness that diabetes has an impact on the CNS and that diabetes is a risk factor for Alzheimer's disease (AD). Links between AD and diabetes point to impaired insulin signaling as a common mechanism leading to defects in the brain. However, diabetes is predominantly characterized by peripheral, rather than central, neuropathy, and despite the common central mechanisms linking AD and diabetes, little is known about the effect of AD on the peripheral nervous system (PNS). In this study, we compared indexes of peripheral neuropathy and investigated insulin signaling in the sciatic nerve of insulin-deficient mice and amyloid precursor protein (APP) overexpressing transgenic mice. Insulin-deficient and APP transgenic mice displayed similar patterns of peripheral neuropathy with decreased motor nerve conduction velocity, thermal hypoalgesia, and loss of tactile sensitivity. Phosphorylation of the insulin receptor and glycogen synthase kinase 3β (GSK3β) was similarly affected in insulin-deficient and APP transgenic mice despite significantly different blood glucose and plasma insulin levels, and nerve of both models showed accumulation of Aβ-immunoreactive protein. Although diabetes and AD have different primary etiologies, both diseases share many abnormalities in both the brain and the PNS. Our data point to common deficits in the insulin-signaling pathway in both neurodegenerative diseases and support the idea that AD may cause disorders outside the higher CNS.

  6. 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

  7. 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

  8. 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

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

    PubMed Central

    Kallianpur, Asha R; Hulgan, Todd

    2009-01-01

    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

  10. 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

  11. Rasch-Transformed Total Neuropathy Score clinical version (RT-TNSc(©) ) in patients with chemotherapy-induced peripheral neuropathy.

    PubMed

    Binda, Davide; Cavaletti, Guido; Cornblath, David R; Merkies, Ingemar S J

    2015-09-01

    Composite scales such as the Total Neuropathy Score clinical version (TNSc(©) ) have been widely used to measure neurological impairment in a standardized manner but they have been criticized due to their ordinal setting having no fixed unit. This study aims to improve impairment assessment in patients with chemotherapy-induced peripheral neuropathy (CIPN) by subjecting TNSc(©) records to Rasch analyses. In particular, we wanted to investigate the influence of factors affecting the use of the TNSc(©) in clinical practice. TNSc(©) has 7 domains (sensory, motor, autonomic, pin-prick, vibration, strength, and deep tendon reflexes [DTR]) each being scored 0-4. Data obtained in 281 patients with stable CIPN were subjected to Rasch analyses to determine the fit to the model. The TNSc(©) did not meet Rasch model's expectations primarily because of misfit statistics in autonomic and DTR domains. Removing these two, acceptable model fit and uni-dimensionality were obtained. However, disordered thresholds (vibration and strength) and item bias (mainly cultural) were still seen, but these findings were kept to balance the assessment range of the Rasch-Transformed TNSc(©) (RT-TNSc(©) ). Acceptable reliability findings were also obtained. A 5-domains RT-TNSc(©) may be a more proper assessment tool in patients with CIPN. Future studies are needed to examine its responsive properties.

  12. Effect of Tongxinluo on nerve regeneration in mice with diabetic peripheral neuropathy.

    PubMed

    Li, X; Zhang, J; Zhao, W; Yang, H; Ma, J; Qi, Y; Wu, S

    2015-01-01

    Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. This study aims to investigate the effects of Tongxinluo on the nerve regeneration in diabetic peripheral neuropathy mice. Forty Specefic Pathogen Free (SPF) male KK/Upj—Ay mice were divided into diabetes group, diabetes with high dose Tongxinluo (4g/kg) (D+H), diabetes with mid dose Tongxinluo (2g/kg) (D+M), and diabetes with low dose Tongxinluo (1g/kg) (D+L) groups. Fasting blood glucose (FPG), heat pain threshold, motor nerve conduction velocity (MNCV), insulin—like growth factor—1 (IGF1), activator protein 1 (c—fos), nerve growth factor (NGF), and basic fibroblast growth factor (BFGF) were measured. Results indicated that FPG of diabetes group was significantly higher than that of control group. Heat pain threshold and MNCV were significantly lowered in diabetes group. Expression levels of IGF1, NGF and BFGF were significantly lower than that of control, whereas c—fos expression was significantly higher than that of control group. Tongxinluo treatment (D+M and D+H) significantly up—regulated heat pain threshold, MNCV, and IGF1, NGF and BFGF expression, but decreased c—fos expresson when compared to that of diabetes group. In conclusion, Tongxinluo can ameliorate diabetic peripheral neuropathy, improve MNCV, and promote nerve regeneration. The underlying mechanism needs to be further elucidated. PMID:26522065

  13. 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.

  14. 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

  15. Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study.

    PubMed

    Boland, Elaine G; Selvarajah, Dinesh; Hunter, Mike; Ezaydi, Yousef; Tesfaye, Solomon; Ahmedzai, Sam H; Snowden, John A; Wilkinson, Iain D

    2014-01-01

    Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN) can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI) to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN) with those from healthy volunteers (HV). Twenty-four participants (n = 12 MM-CIPN, n = 12 HV) underwent Blood Oxygen Level-Dependent (BOLD) fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected). Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected). Significant positive correlation existed between the total neuropathy score (reduced version) and activation in the frontal operculum (close to insular cortex) during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87). Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

  16. 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

  17. [Measurement of antiganglioside autoantibodies by immunodot-blot assay: clinical importance in peripheral neuropathies].

    PubMed

    Caudie, C; Vial, C; Petiot, P; Bancel, J; Later, R; Gonnaud, P M

    1999-01-01

    We retrospectively evaluated measurement data and clinical relevance of autoantibodies to gangliosides in peripheral neuropathies (PN). The IgG and IgM antiganglioside autoantibodies were determined by our own immunodot-blot assay on membrane and by enzyme-linked immunosorbent assay (Elisa) in sera of 1,342 patients with peripheral neuropathies. Anti-GM1 and anti-GD1b autoantibodies formed a part of the normal autoantibody repertoire and were common place in 12% of normal subjects and in 14% of disease control groups. Polyclonal IgM antiganglioside autoantibodies were detected in chronic PN, polyclonal IgG antiganglioside autoantibodies were detected in acute PN. Polyclonal IgM anti-GM1 and anti-GD1b autoantibodies were detected in 35 patients out of 48 with treatable multifocal motor neuropathy with persistent conduction blocks. These autoantibodies well discriminated between suspected motor peripheral neuropathies and motor neuron diseases (sensitivity 73%, specificity 83%, positive predictive value 60%, negative predictive value 91%). Monoclonal IgM autoantibodies reacted strongly with gangliosides in 15 patients out of 77 with M-IgM neuropathy (19%). M-IgM autoantibodies differed in their fine specificities with different principal target antigens as demonstrated with cross-reactivity. Such findings provide further evidence for a relationship between neurological syndromes and antiganglioside antibody profiles and also suggest that different gangliosides could be principal target antigens such as GM1, GD1b, GT1b, GD1a or GM2. Polyclonal IgG anti-GM1 and anti-GD1b autoantibodies were detected in 21 patients out of 22 with acute motor axonal Guillain-Barré syndrome with antecedent of infection by Campylobacter jejuni, polyclonal IgG anti-GQ1b autoantibodies in 9 patients out of 10 with Miller-Fisher syndrome. Detection of antiganglioside autoantibodies by immunodot-blot assay which is simple and quick in testing a large panel of gangliosides has become very

  18. 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

  19. Diabetic neuropathy.

    PubMed

    Vinik, Aaron I; Nevoret, Marie-Laure; Casellini, Carolina; Parson, Henri

    2013-12-01

    Diabetic neuropathy (DN) is the most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care. The clinical assessment of diabetic peripheral neuropathy and its treatment options are multifactorial. Patients with DN should be screened for autonomic neuropathy, as there is a high degree of coexistence of the two complications. A review of the clinical assessment and treatment algorithms for diabetic neuropathy, painful neuropathy, and autonomic dysfunction is provided.

  20. 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

  1. Ultrasound in the diagnosis of peripheral neuropathy: structure meets function in the neuromuscular clinic.

    PubMed

    Gallardo, Elena; Noto, Yu-Ichi; Simon, Neil G

    2015-10-01

    Peripheral nerve ultrasound (US) has emerged as a promising technique for the diagnosis of peripheral nerve disorders. While most experience with US has been reported in the context of nerve entrapment syndromes, the role of US in the diagnosis of peripheral neuropathy (PN) has recently been explored. Distinctive US findings have been reported in patients with hereditary, immune-mediated, infectious and axonal PN; US may add complementary information to neurophysiological studies in the diagnostic work-up of PN. This review describes the characteristic US findings in PN reported to date and a classification of abnormal nerve US patterns in PN is proposed. Closer scrutiny of nerve abnormalities beyond assessment of nerve calibre may allow for more accurate diagnostic classification of PN, as well as contribute to the understanding of the intersection of structure and function in PN.

  2. Diabetic peripheral neuropathy class prediction by multicategory support vector machine model: a cross-sectional study

    PubMed Central

    2016-01-01

    OBJECTIVES Diabetes is increasing in worldwide prevalence, toward epidemic levels. Diabetic neuropathy, one of the most common complications of diabetes mellitus, is a serious condition that can lead to amputation. This study used a multicategory support vector machine (MSVM) to predict diabetic peripheral neuropathy severity classified into four categories using patients’ demographic characteristics and clinical features. METHODS In this study, the data were collected at the Diabetes Center of Hamadan in Iran. Patients were enrolled by the convenience sampling method. Six hundred patients were recruited. After obtaining informed consent, a questionnaire collecting general information and a neuropathy disability score (NDS) questionnaire were administered. The NDS was used to classify the severity of the disease. We used MSVM with both one-against-all and one-against-one methods and three kernel functions, radial basis function (RBF), linear, and polynomial, to predict the class of disease with an unbalanced dataset. The synthetic minority class oversampling technique algorithm was used to improve model performance. To compare the performance of the models, the mean of accuracy was used. RESULTS For predicting diabetic neuropathy, a classifier built from a balanced dataset and the RBF kernel function with a one-against-one strategy predicted the class to which a patient belonged with about 76% accuracy. CONCLUSIONS The results of this study indicate that, in terms of overall classification accuracy, the MSVM model based on a balanced dataset can be useful for predicting the severity of diabetic neuropathy, and it should be further investigated for the prediction of other diseases. PMID:27032459

  3. Molecular alterations resulting from frameshift mutations in peripheral myelin protein 22: implications for neuropathy severity.

    PubMed

    Johnson, J S; Roux, K J; Fletcher, B S; Fortun, J; Notterpek, L

    2005-12-15

    Alterations in peripheral myelin protein 22 (PMP22) expression are associated with a heterogeneous group of hereditary demyelinating peripheral neuropathies. Two mutations at glycine 94, a single guanine insertion or deletion in PMP22, result in different reading frameshifts and, consequently, an extended G94fsX222 or a truncated G94fsX110 protein, respectively. Both of these autosomal dominant mutations alter the second half of PMP22 and yet are linked to clinical phenotypes with distinct severities. The G94fsX222 is associated with hereditary neuropathy with liability to pressure palsies, whereas G94fsX110 causes severe neuropathy diagnosed as Dejerine-Sottas disease or Charcot-Marie-Tooth disease type IA. To investigate the subcellular changes associated with the G94 frameshift mutations, we expressed epitope-tagged forms in primary rat Schwann cells. Biochemical and immunolabeling studies indicate that, unlike the wild-type protein, which is targeted for the plasma membrane, frameshift PMP22s are retained in the cell, prior to reaching the medial Golgi compartment. Similar to Wt-PMP22, both frameshift mutants are targeted for proteasomal degradation and accumulate in detergent-insoluble, ubiquitin-containing aggregates upon inhibition of this pathway. The extended frameshift PMP22 shows the ability to form spontaneous aggregates in the absence of proteasome inhibition. On the other hand, Schwann cells expressing the truncated protein proliferate at a significantly higher rate than Schwann cells expressing the wild-type or the extended PMP22. In summary, these results suggest that a greater potential for PMP22 aggregation is associated with a less severe phenotype, whereas dysregulation of Schwann cell proliferation is linked to severe neuropathy. PMID:16273544

  4. Ultrasound assessment on selected peripheral nerve pathologies. Part I: Entrapment neuropathies of the upper limb - excluding carpal tunnel syndrome.

    PubMed

    Kowalska, Berta; Sudoł-Szopińska, Iwona

    2012-09-01

    Ultrasound (US) is one of the methods for imaging entrapment neuropathies, post-traumatic changes to nerves, nerve tumors and postoperative complications to nerves. This type of examination is becoming more and more popular, not only for economic reasons, but also due to its value in making accurate diagnosis. It provides a very precise assessment of peripheral nerve trunk pathology - both in terms of morphology and localization. During examination there are several options available to the specialist: the making of a dynamic assessment, observation of pain radiation through the application of precise palpation and the comparison of resultant images with the contra lateral limb. Entrapment neuropathies of the upper limb are discussed in this study, with the omission of median nerve neuropathy at the level of the carpal canal, as extensive literature on this subject exists. The following pathologies are presented: pronator teres muscle syndrome, anterior interosseus nerve neuropathy, ulnar nerve groove syndrome and cubital tunnel syndrome, Guyon's canal syndrome, radial nerve neuropathy, posterior interosseous nerve neuropathy, Wartenberg's disease, suprascapular nerve neuropathy and thoracic outlet syndrome. Peripheral nerve examination technique has been presented in previous articles presenting information about peripheral nerve anatomy [Journal of Ultrasonography 2012; 12 (49): 120-163 - Normal and sonographic anatomy of selected peripheral nerves. Part I: Sonohistology and general principles of examination, following the example of the median nerve; Part II: Peripheral nerves of the upper limb; Part III: Peripheral nerves of the lower limb]. In this article potential compression sites of particular nerves are discussed, taking into account pathomechanisms of damage, including predisposing anatomical variants (accessory muscles). The parameters of ultrasound assessment have been established - echogenicity and echostructure, thickness (edema and related increase

  5. Platelet-Rich Plasma Guided Injections: Clinical Application in Peripheral Neuropathies

    PubMed Central

    Malahias, Michael-Alexander; Chytas, Dimitrios; Babis, George C.; Nikolaou, Vasileios S.

    2014-01-01

    Platelet-rich plasma (PRP) is defined as an autologous concentrated preparation of platelets and their associated growth factors in a small volume of plasma. The presence of these growth factors has stimulated the scientific community to search about possible benefits of the use of PRP in tissue regeneration. Provided that previously in vitro and animal research demonstrated that PRP could probably play an important role in the treatment of neural tissue disorders, we aimed to review the current literature, regarding the clinical studies that have been conducted to confirm this hypothesis. More specifically, we have reviewed the literature concerning the clinical application of PRP in peripheral neuropathies and investigated if there is strong evidence to establish the use of PRP in clinical practice as a therapeutic option. In contrast with animal studies, we have been able to identify only few clinical data concerning the use of PRP in peripheral neuropathies. We found five trials matched to our research that yields positive and promising results for the future for the application of PRP for the therapy of disorders of the peripheral nervous system. It is obvious that this interesting field of research gives to the scientists the ability to expand it extensively, in terms of both quality and quantity. PMID:25593965

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. Caspr1/Paranodin/Neurexin IV is most likely not a common disease-causing gene for inherited peripheral neuropathies.

    PubMed

    Venken, K; Meuleman, J; Irobi, J; Ceuterick, C; Martini, R; De Jonghe, P; Timmerman, V

    2001-08-01

    Contactin associated protein 1 (Caspr1/Paranodin/Neurexin IV) is an axonal transmembrane molecule mainly localised at the paranodal junction. Since molecular alterations in septate-like junctions at the paranodes might have important consequences for the function of the nerve fiber, we considered that Caspr1 could be involved in the pathogenesis of inherited peripheral neuropathies. In this study, we physically mapped the Caspr1 gene on chromosome 17q21.1 and determined its genomic structure. We performed a mutation analysis of the Caspr1 gene in a cohort of 64 unrelated patients afflicted with distinct inherited peripheral neuropathies. Since no disease causing mutations were found, we suggest that Caspr1 is probably not a common cause of inherited peripheral neuropathies. PMID:11496158

  12. Cycloserine Induced Late Onset Psychosis and Ethambutol Induced Peripheral Neuropathy Associated with MDR-TB Treatment in an Indian Patient- A Rare Case Report

    PubMed Central

    Holla, Sadhana; Bhandarypanambur, Rajeshkrishna; Kamalkishore, Meenakumari; Janardhanan, Manju

    2015-01-01

    Adverse reactions and toxicity inevitably accompany all treatment courses for drug-resistant TB. Our case underscores the importance of awareness regarding neuropsychiatric adverse reactions due to MDR-TB therapy and reversible nature of it. Cycloserine induced psychosis is most life threatening complication and sometimes could be fatal. A 42-year-old male on MDR-TB therapy got admitted for his persistent psychotic complaints like hallucinations, delusions and suicidal ideations, despite being treated with quetiapine/olanzapine. Eventually patient was rehabilitated, cycloserine was stopped and psychotic events regressed slowly. Other culprit drugs like ethambutol and levofloxacin causing psychosis was ruled out because there was no relapse of psychotic events despite being continued with these drugs. He also complained of tingling, numbness, swaying, pain and weakness. On examination, he had distal motor weakness in lower limbs, tandem gait positive, altered position sense, and tenderness over toes and positive Romberg’s sign with ataxia. He was diagnosed to have drug induced sensorimotor peripheral neuropathy. All these symptoms persisted after stopping cycloserine and patient continued to have neuropathy with ethambutol and ethionamide. Considering the nature of neuropathy which was mild, mixed sensorimotor and resolved completely after 2-3 weeks of stopping, it was more in favour of ethambutol. However, we could not rule out the possibility of ethionamide or (ethionamide + ethambutol) causing neuropathy or both could have accelerated the neurotoxic effects of cycloserine which remained elusive. PMID:25859468

  13. Defective Aire-Dependent Central Tolerance to P0 Is Linked to Autoimmune Peripheral Neuropathy

    PubMed Central

    Su, Maureen A.; Davini, Dan; Cheng, Philip; Giang, Karen; Fan, Una; DeVoss, Jason J.; Johannes, Kellsey P.A.; Taylor, Lorelei; Shum, Anthony K.; Valenzise, Mariella; Meloni, Antonella; Bour-Jordan, Helene; Anderson, Mark S.

    2012-01-01

    Chronic Inflammatory Demyelinating Polyneuropathy is a debilitating autoimmune disease characterized by peripheral nerve demyelination and dysfunction. How the autoimmune response is initiated, identity of provoking antigens, and pathogenic effector mechanisms are not well-defined. The Autoimmune Regulator (Aire) plays a critical role in central tolerance by promoting thymic expression of self-antigens and deletion of self-reactive T cells. Here, we utilized mice with hypomorphicAire function and two patients with Aire mutations to define how Aire deficiency results in spontaneous autoimmune peripheral neuropathy. Autoimmunity against peripheral nerves in both mice and humans targets Myelin Protein Zero (P0), an antigen whose expression is Aire-regulated in the thymus. Consistent with a defect in thymic tolerance, CD4+ T cells are sufficient to transfer disease in mice and produce IFN-gamma in infiltrated peripheral nerves. Our findings suggest that defective Aire-mediated central tolerance to P0 initiates an autoimmune Th1 effector response toward peripheral nerves. PMID:22490868

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Divergent effects of T cell costimulation and inflammatory cytokine production on autoimmune peripheral neuropathy provoked by Aire deficiency.

    PubMed

    Zeng, Xiaopei L; Nagavalli, Anil; Smith, Colin-Jamal; Howard, James F; Su, Maureen A

    2013-04-15

    Chronic inflammatory demyelinating polyneuropathy results from autoimmune destruction of the peripheral nervous system and is a component of the multiorgan autoimmunity syndrome that results from Aire gene mutations in humans. In parallel, peripheral nervous system autoimmunity resembling chronic inflammatory demyelinating polyneuropathy develops spontaneously in NOD mice with a partial loss of Aire function (NOD.Aire(GW/+) mice) and is a T cell-mediated disease. In this study, we analyze how key aspects of T cell activation and function modulate disease development in Aire-deficient mice. We show that genetic ablation of the Th1 cytokine IFN-γ completely prevents clinical and electrophysiological evidence of neuropathy in NOD.Aire(GW/+) mice. IFN-γ deficiency is associated with absence of immune infiltration and decreased expression of the T cell chemoattractant IP-10 in sciatic nerves. Thus, IFN-γ is absolutely required for the development of autoimmune peripheral neuropathy in NOD.Aire(GW/+) mice. Because IFN-γ secretion is enhanced by B7-CD28 costimulation of T cells, we sought to determine the effects of these costimulatory molecules on neuropathy development. Surprisingly, B7-2 deficiency accelerated neuropathy development in NOD.Aire(GW/+) mice, and Ab blockade of both B7-1 and B7-2 resulted in fulminant, early-onset neuropathy. Thus, in contrast to IFN-γ, B7-2 alone and B7-1/B7-2 in combination function to ameliorate neuropathy development in NOD.Aire(GW/+) mice. Together, these findings reveal distinct and opposing effects of the T cell costimulatory pathway and IFN-γ production on the pathogenesis of autoimmune peripheral neuropathy.

  5. 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

  6. Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy: a meta-analysis of 16 randomized controlled trials

    PubMed Central

    Pang, Bing; Zhao, Tian-yu; Zhao, Lin-hua; Wan, Fang; Ye, Ru; Zhou, Qiang; Tian, Feng; Tong, Xiao-lin

    2016-01-01

    OBJECTIVE: This meta-analysis was performed to systematically assess the efficacy and safety of the Chinese herbal medicine Huangqi Guizhi Wuwu Decoction (HGWWD) for treating diabetic peripheral neuropathy. DATA SOURCES: Six electronic databases, including the Cochrane Library, MEDLINE database, Chinese Biomedical Database, Chinese National Knowledge Infrastructure Database, Chinese Science and Technique Journals Database, and the Wanfang Database, were searched on the internet for randomized controlled trials published up until 1 December 2015. The search terms included “Chinese herbal medicine”, “diabetic peripheral neuropathy” and “randomized controlled trials” in Chinese and in English. DATA SELECTION: We included randomized controlled trials using HGWWD/modified HGWWD for the treatment group, without restriction for the control group. We assessed literature quality in accordance with the Cochrane Review Handbook. A random or a fixed effects model was used to analyze outcomes using RevMan 5.2 software. OUTCOME MEASURES: The primary outcomes were changes in symptoms and nerve conduction velocities. The secondary outcomes were fasting blood glucose and hemorheological indexes. RESULTS: Sixteen randomized controlled trials, with a total of 1,173 patients, were included. Meta-analysis revealed that the efficacy of HGWWD for diabetic peripheral neuropathy was significantly superior compared with the control treatment (i.e., control group) (risk ratio = 0.36, 95% confidence interval (CI): 0.29–0.46, Z =8.33, P < 0.00001) Compared with the control group, there was an increase in median motor nerve conduction velocity (mean difference (MD) = 3.46, 95%CI: 1.88–5.04, Z = 4.30, P < 0.01) and median sensory nerve conduction velocity (MD = 3.30, 95%CI: 2.04–4.56, Z = 5.14, P < 0.01). There was also an increase in peroneal motor nerve conduction velocity (MD = 3.22, 95%CI: 2.45–3.98, Z = 8.21, P < 0.01) and peroneal sensory nerve conduction velocity (MD

  7. Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy: a meta-analysis of 16 randomized controlled trials

    PubMed Central

    Pang, Bing; Zhao, Tian-yu; Zhao, Lin-hua; Wan, Fang; Ye, Ru; Zhou, Qiang; Tian, Feng; Tong, Xiao-lin

    2016-01-01

    OBJECTIVE: This meta-analysis was performed to systematically assess the efficacy and safety of the Chinese herbal medicine Huangqi Guizhi Wuwu Decoction (HGWWD) for treating diabetic peripheral neuropathy. DATA SOURCES: Six electronic databases, including the Cochrane Library, MEDLINE database, Chinese Biomedical Database, Chinese National Knowledge Infrastructure Database, Chinese Science and Technique Journals Database, and the Wanfang Database, were searched on the internet for randomized controlled trials published up until 1 December 2015. The search terms included “Chinese herbal medicine”, “diabetic peripheral neuropathy” and “randomized controlled trials” in Chinese and in English. DATA SELECTION: We included randomized controlled trials using HGWWD/modified HGWWD for the treatment group, without restriction for the control group. We assessed literature quality in accordance with the Cochrane Review Handbook. A random or a fixed effects model was used to analyze outcomes using RevMan 5.2 software. OUTCOME MEASURES: The primary outcomes were changes in symptoms and nerve conduction velocities. The secondary outcomes were fasting blood glucose and hemorheological indexes. RESULTS: Sixteen randomized controlled trials, with a total of 1,173 patients, were included. Meta-analysis revealed that the efficacy of HGWWD for diabetic peripheral neuropathy was significantly superior compared with the control treatment (i.e., control group) (risk ratio = 0.36, 95% confidence interval (CI): 0.29–0.46, Z =8.33, P < 0.00001) Compared with the control group, there was an increase in median motor nerve conduction velocity (mean difference (MD) = 3.46, 95%CI: 1.88–5.04, Z = 4.30, P < 0.01) and median sensory nerve conduction velocity (MD = 3.30, 95%CI: 2.04–4.56, Z = 5.14, P < 0.01). There was also an increase in peroneal motor nerve conduction velocity (MD = 3.22, 95%CI: 2.45–3.98, Z = 8.21, P < 0.01) and peroneal sensory nerve conduction velocity (MD

  8. Arsenical neuropathy: residual effects following acute industrial exposure.

    PubMed

    Garb, L G; Hine, C H

    1977-08-01

    A case report is presented describing a worker who was splashed with arsenic acid in an industrial accident and subsequently developed symptoms of systemic arsenicalism and peripheral neuropathy. This is the only report, to the authors' knowledge, of a single episode of cutaneous absorption of arsenic resulting in peripheral neuropathy. Previous reports of arsenical neuropathy and rationale for BAL therapy early in the treatment of systemic arsenicalism are discussed.

  9. Is the C677T polymorphism in methylenetetrahydrofolate reductase gene or plasma homocysteine a risk factor for diabetic peripheral neuropathy in Chinese individuals?

    PubMed

    Wang, Hongli; Fan, Dongsheng; Hong, Tianpei

    2012-10-25

    The present study enrolled 251 diabetic patients, including 101 with neuropathy and 150 without neuropathy. Of the 150 patients, 100 had no complications, such as retinopathy, nephropathy, or neuropathy. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to identify methylenetetrahydrofolate reductase gene variants. Plasma homocysteine levels were also measured. Homocysteine levels and the frequency of hyperhomocysteinemia were significantly higher in patients with diabetic peripheral neuropathy compared with diabetic patients without neuropathy (P < 0.05). In logistic regression analysis with neuropathy as the dependent variable, the frequency of C677T in methylenetetrahydrofolate reductase was significantly higher in patients with diabetic peripheral neuropathy compared with patients without diabetic complications. Homocysteine levels were significantly higher in patients with diabetic peripheral neuropathy carrying the 677T allele and low folic acid levels. In conclusion, hyperhomocysteinemia is an independent risk factor for diabetic neuropathy in Chinese patients with diabetes. The C677T polymorphism in methylenetetrahydrofolate reductase and low folic acid levels may be risk factors for diabetic peripheral neuropathy in Chinese patients with diabetes.

  10. 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.

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

    PubMed Central

    Yilmaz, E; Gold, MS

    2015-01-01

    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 Ca2+ concentration ([Ca2+]i) in subpopulations of cutaneous neurons. To test this prediction, we characterized the pattern of changes in mechanical nociceptive threshold associated with paclitaxel administration (2 mg/kg, iv, every other day for four days), as well as the impact of target of innervation and paclitaxel treatment on the regulation of [Ca2+]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 [Ca2+]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 [Ca2+]i was significantly lower in neurons innervating the thigh after treatment. The magnitude of the depolarization-evoked Ca2+ transient was also lower in putative non-nociceptive thigh neurons. More interestingly, while paclitaxel had no detectable influence on either resting or depolarization-evoked Ca2+ transients in putative non-nociceptive neurons, in putative nociceptive neurons there was a subpopulation- specific decrease in the duration of the evoked Ca2+ 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:25982563

  12. 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

  13. 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

  14. 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

  15. 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

  16. Skeletal muscle MRI magnetisation transfer ratio reflects clinical severity in peripheral neuropathies.

    PubMed

    Sinclair, C D J; Morrow, J M; Miranda, M A; Davagnanam, I; Cowley, P C; Mehta, H; Hanna, M G; Koltzenburg, M; Yousry, T A; Reilly, M M; Thornton, J S

    2012-01-01

    MRI may provide treatment outcome measures in neuromuscular conditions. The authors assessed MRI magnetisation transfer ratios (MTRs) in lower-limb musculature as markers of pathology in peripheral neuropathies and compared the findings with associated clinical data. Ten patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) were compared with 10 healthy subjects. The MTR in the calf muscles was significantly lower than controls in the two patient groups (both p<0.001). The median MTRs (IQR) were 50.5(1.6) percentage units (p.u.) (control), 41.5(10.6) p.u. (CMT1A) and 39.3(8.7) p.u. (CIDP). Moreover, anterior lower leg MTR correlated strongly with strength of ankle dorsiflexion, measured with the Medical Research Council scale, in CIDP (ρ=0.88, p<0.001) and also in CMT1A (ρ=0.50, p<0.05), where MTR also showed an association with disease duration (ρ=-0.86, p<0.001). Short tau inversion recovery MRI of the same muscles showed abnormalities associated with regions of reduced MTR (p<0.001), and MTR was also reduced in other muscles otherwise deemed normal appearing (p<0.001), indicating that MTR may be more sensitive to muscle damaged by denervation than conventional MRI. The significant reductions in muscle MTR in peripheral neuropathies and the associated correlations with clinical measures indicate that MTR has potential as an imaging outcome measure in future therapeutic trials.

  17. 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.

  18. Safety of Aerobic Exercise in People With Diabetic Peripheral Neuropathy: Single-Group Clinical Trial

    PubMed Central

    Pasnoor, Mamatha; Singh, Rupali; D'Silva, Linda J.; Yoo, Min; Billinger, Sandra A.; LeMaster, Joseph W.; Dimachkie, Mazen M.; Herbelin, Laura; Wright, Douglas E.

    2015-01-01

    Background Exercise is recommended for people with diabetes, but little is known about exercise in people with diabetic peripheral neuropathy (DPN). Objective The primary purpose of this preliminary study was to examine adverse events (AEs) during moderate-intensity, supervised aerobic exercise in people with DPN. The secondary purpose was to examine changes in fatigue, aerobic fitness, and other outcomes after intervention. Design This was a single-group preliminary study. Setting The setting was an academic medical center. Participants Participants were 18 people who were sedentary and had type 2 diabetes and peripheral neuropathy (mean age=58.1 years, SD=5). Intervention The intervention was a supervised 16-week aerobic exercise program (3 times per week at 50% to >70% oxygen uptake reserve). Measurements Adverse events were categorized as related or unrelated to the study, anticipated or unanticipated, and serious or not serious. Outcomes included fatigue (Multidimensional Fatigue Inventory), cardiovascular fitness (peak oxygen uptake), body composition (dual-energy x-ray absorptiometry), sleep quality, plasma metabolic markers, and peripheral vascular function. Results During the study, 57 nonserious AEs occurred. Improvements were found in general fatigue (mean change=−3.5; 95% confidence interval [95% CI]=−1.3, −5.3), physical fatigue (mean change=−3.1; 95% CI=−1.2, −5.0), peak oxygen uptake (mean change=1.1 mL·kg−1·min−1; 95% CI=0.2, 1.9), total body fat (mean change=−1%; 95% CI=−0.3, −1.7), fat mass (mean change=−1,780 g; 95% CI=−616.2, −2,938.7), and peripheral blood flow (mean change=2.27%; 95% CI=0.6, 4.0). Limitations This was a small-scale, uncontrolled study. A future randomized controlled trial is needed to fully assess the effects of exercise on the outcomes. Conclusions This study provides new support for supervised aerobic exercise in people with DPN. However, it is important for physical therapists to carefully

  19. Hereditary sensory neuropathies.

    PubMed

    Auer-Grumbach, Michaela

    2004-05-01

    Hereditary sensory neuropathies (HSNs) are a group of genetically determined peripheral neuropathies with prominent disturbance of the peripheral sensory neurons. They are characterized by sensory loss, insensitivity to pain, a variable degree of muscle weakness and wasting, as well as autonomic features. Frequent complications are foot ulcerations and infections that may lead to osteomyelitis, followed by necrosis and amputations. Consequently, the hereditary sensory neuropathies have also been termed ulceromutilating neuropathies. On the other hand, in the presence of additional motor weakness, they have been subclassified among the group of Charcot-Marie-Tooth (CMT) disorders. Sporadic and familial cases with different modes of inheritance are known to affect both children and adults. The most prevalent forms of the autosomal dominantly inherited hereditary sensory neuropathies are HSN I and CMT 2b. HSN I is associated with mutations in the SPTLC1 gene, whereas mutations in the RAB7 gene have been identified in CMT 2b. However, at least one more hitherto unknown gene responsible for autosomal-dominant hereditary sensory neuropathies must exist. Autosomal-recessive hereditary sensory neuropathies types III and IV, and probably also type V, result from mutations in the IKBKAP and NTRK1 genes. Very recently, the gene in HSN II (HSN2) has been identified. A spontaneous autosomal-recessive mutation in the Cct4 gene has been reported in the Sprague-Dawley rat strain with early onset sensory neuropathy. Although no curative treatment is available so far, and current therapy is limited to symptom relief, these molecular genetic advances in knowledge about the hereditary sensory neuropathies can be translated into clinical practice by improving diagnosis and genetic counseling. They will also be the basis for functional studies in the future. PMID:15319794

  20. How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

    PubMed

    Truini, Andrea; Cruccu, Giorgio

    2016-02-01

    Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

  1. Long-term evaluation of Leber's hereditary optic neuropathy-like symptoms in rotenone administered rats.

    PubMed

    Zhang, Li; Liu, Laura; Philip, Ann L; Martinez, Juan C; Guttierez, Juan C; Marella, Mathieu; Patki, Gaurav; Matsuno-Yagi, Akemi; Yagi, Takao; Thomas, Biju B

    2015-01-12

    Leber's hereditary optic neuropathy (LHON) is an inherited disorder affecting the retinal ganglion cells (RGCs) and their axons that lead to the loss of central vision. This study is aimed at evaluating the LHON symptoms in rats administered with rotenone microspheres into the superior colliculus (SC). Optical coherence tomography (OCT) analysis showed substantial loss of retinal nerve fiber layer (RNFL) thickness in rotenone injected rats. Optokinetic testing in rotenone treated rats showed decrease in head-tracking response. Electrophysiological mapping of the SC surface demonstrated attenuation of visually evoked responses; however, no changes were observed in the ERG data. The progressive pattern of disease manifestation in rotenone administered rats demonstrated several similarities with human disease symptoms. These rats with LHON-like symptoms can serve as a model for future investigators to design and implement reliable tests to assess the beneficial effects of therapeutic interventions for LHON disease.

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

    PubMed

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

    2015-11-01

    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.

  3. 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

  4. 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

  5. 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

  6. Search for mutations in the EGR2 corepressor proteins, NAB1 and NAB2, in human peripheral neuropathies.

    PubMed

    Venken, Koen; Di Maria, Emilio; Bellone, Emilia; Balestra, Piercesare; Cassandrini, Denise; Mandich, Paola; De Jonghe, Peter; Timmerman, Vincent; Svaren, John

    2002-03-01

    EGR2/Krox-20, a Cys2-His2 zinc finger transcription factor, plays an essential role in the regulation of myelination in the peripheral nervous system. Dominant and recessive mutations in EGR2 are associated with peripheral myelinopathies, such as Charcot-Marie-Tooth disease type 1, Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy. One recessive mutation (I268N) is known to affect the inhibitory domain that binds the NAB transcriptional corepressors, NAB1 and NAB2. This mutation abolishes the interaction of EGR2 with the NAB corepressors and thereby increases transcriptional activity. Therefore, we hypothesized that mutations in the EGR2-interacting domains of NAB1 and NAB2 might be associated with the pathogenesis of inherited peripheral neuropathies in currently unexplained cases. However, screening 87 such cases failed to identify any disease-causing mutations within the EGR2-interacting domains of either NAB1 or NAB2. A further mutation analysis of the complete coding regions of NAB1 and NAB2 in these genomic DNA samples did not uncover any disease-causing mutation. Therefore, our analysis indicates that mutations in the human NABI and NAB2 genes are most likely not involved in the pathogenesis of peripheral neuropathies. PMID:12030330

  7. Inhibition of anandamide hydrolysis attenuates nociceptor sensitization in a murine model of chemotherapy-induced peripheral neuropathy

    PubMed Central

    Uhelski, Megan L.; Khasabova, Iryna A.

    2014-01-01

    Painful neuropathy frequently develops as a consequence of commonly used chemotherapy agents for cancer treatment and is often a dose-limiting side effect. Currently available analgesic treatments are often ineffective on pain induced by neurotoxicity. Although peripheral administration of cannabinoids, endocannabinoids, and inhibitors of endocannabinoid hydrolysis has been effective in reducing hyperalgesia in models of peripheral neuropathy, including chemotherapy-induced peripheral neuropathy (CIPN), few studies have examined cannabinoid effects on responses of nociceptors in vivo. In this study we determined whether inhibition of fatty acid amide hydrolase (FAAH), which slows the breakdown of the endocannabinoid anandamide (AEA), reduced sensitization of nociceptors produced by chemotherapy. Over the course of a week of daily treatments, mice treated with the platinum-based chemotherapy agent cisplatin developed robust mechanical allodynia that coincided with sensitization of cutaneous C-fiber nociceptors as indicated by the development of spontaneous activity and increased responses to mechanical stimulation. Administration of the FAAH inhibitor URB597 into the receptive field of sensitized C-fiber nociceptors decreased spontaneous activity, increased mechanical response thresholds, and decreased evoked responses to mechanical stimuli. Cotreatment with CB1 (AM281) or CB2 (AM630) receptor antagonists showed that the effect of URB597 was mediated primarily by CB1 receptors. These changes following URB597 were associated with an increase in the endocannabinoid anandamide in the skin. Our results suggest that enhanced signaling in the peripheral endocannabinoid system could be utilized to reduce nociceptor sensitization and pain associated with CIPN. PMID:25505113

  8. Efficacy of Japanese traditional (Kampo) medicine for treating chemotherapy-induced peripheral neuropathy: A retrospective case series study

    PubMed Central

    Kimata, Yumiko; Ogawa, Keiko; Okamoto, Hideki; Chino, Atsushi; Namiki, Takao

    2016-01-01

    AIM To investigate Japanese traditional (Kampo) medicine’s effectiveness on cancer chemotherapy-induced peripheral neuropathy (CIPN), we carried out this retrospective study. METHODS By searching our outpatient database of 3154 patients who consulted our outpatient clinic of Japanese-Oriental (Kampo) Medicine at Chiba University Hospital from November 2005 to December 2010, a total of 281 patients diagnosed with cancer were identified. Twenty-four patients out of the 281 patients identified met the following three conditions and were eligible for further investigation of the effectiveness of Kampo treatment: At least one course of cancer chemotherapy had been administered; numbness and pain appeared after the chemotherapy; and CIPN was diagnosed before they were given Kampo treatment. RESULTS The 24 patients included 6 males and 18 females and ranged in age from 39 to 86 (mean 61.2 ± 11.5) years old. Kampo formulas were individually chosen by Kampo expert doctors based on Kampo-specific diagnostics. Beneficial outcomes were obtained by Kampo treatment in 20 out of the 24 cases (83.3%). Nine out 20 cases had a major response (the numbness and pain showed improvement or reduction by 50% or more), with 7 of 9 cases showing a more than 70% symptom reduction. Eleven out of 20 cases showed a minor response (less than 50% symptom reduction), and 4 out of the 24 cases had no beneficial response. The most frequently used formula was goshajinkigan (GJG), followed by hachimijiogan (HJG) and keishibukuryogan. Thirteen of the 24 cases (54.2%) were prescribed aconite root-containing formulas including GJG and HJG. Aconite root has “warming” effects and ameliorates pain and numbness; 21 out of 24 cases (87.5%) in total used warming formulas such as aconite root-containing formulas to reduce CIPN. CONCLUSION Our current study suggested that Kampo formulas chosen based on Kampo-specific diagnostics could be for treating CIPN that is refractory to conventional medicine. PMID

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

    PubMed

    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.

  10. 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

  11. 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

  12. 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

  13. Comparison of shoe-length fit between people with and without diabetic peripheral neuropathy: a case–control study

    PubMed Central

    2012-01-01

    Background Amongst the many identified mechanisms leading to diabetic foot ulceration, ill-fitting footwear is one. There is anecdotal evidence that people with diabetic peripheral neuropathy wear shoes that are too small in order to increase the sensation of fit. The aim of this study was to determine whether people with diabetic sensory neuropathy wear appropriate length footwear. Methods A case–control design was used to compare internal shoe length and foot length differences between a group of people with diabetes and peripheral sensory neuropathy and a group of people without diabetes and no peripheral sensory neuropathy. Shoe and foot length measurements were taken using a calibrated Internal Shoe Size Gauge® and a Brannock Device®, respectively. Results Data was collected from 85 participants with diabetes and 118 participants without diabetes. The mean difference between shoe and foot length was not significantly different between the two groups. However, a significant number of participants within both groups had a shoe to foot length difference that lay outside a previously suggested 10 to 15 mm range. From the diabetic and non-diabetic groups 82% (70/85) and 66% (78/118), respectively had a foot to shoe length difference outside this same range. Conclusions This study shows that although there is no significant difference in shoe-length fit between participants with and without neuropathy, a significant proportion of these populations wear shoes that are either too long or too short for their foot length according to the 10 to 15 mm value used for comparison. The study has highlighted the need for standardised approaches when considering the allowance required between foot and internal shoe length and for the measurement and comparison of foot and shoe dimensions. PMID:22507446

  14. 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

  15. Neuropathic Pain Model of Peripheral Neuropathies Mediated by Mutations of Glycyl-tRNA Synthetase

    PubMed Central

    2014-01-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. Previous studies have found that, according to CMT patients, neuropathic pain is an occasional symptom of CMT. However, neuropathic pain is not considered to be a significant symptom associated with CMT and, as a result, no studies have investigated the pathophysiology underlying neuropathic pain in this disorder. Thus, the first animal model of neuropathic pain was developed by our laboratory using an adenovirus vector system to study neuropathic pain in CMT. To this end, glycyl-tRNA synthetase (GARS) fusion proteins with a FLAG-tag (wild type [WT], L129P and G240R mutants) were expressed in spinal cord and dorsal root ganglion (DRG) neurons using adenovirus vectors. It is known that GARS mutants induce GARS axonopathies, including CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V). Additionally, the morphological phenotypes of neuropathic pain in this animal model of GARS-induced pain were assessed using several possible markers of pain (Iba1, pERK1/2) or a marker of injured neurons (ATF3). These results suggest that this animal model of CMT using an adenovirus may provide information regarding CMT as well as a useful strategy for the treatment of neuropathic pain. Graphical Abstract PMID:25120326

  16. Neuropathic pain model of peripheral neuropathies mediated by mutations of glycyl-tRNA synthetase.

    PubMed

    Lee, Seo Jin; Seo, Ah Jung; Park, Byung Sun; Jo, Hyun Woo; Huh, Youngbuhm

    2014-08-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. Previous studies have found that, according to CMT patients, neuropathic pain is an occasional symptom of CMT. However, neuropathic pain is not considered to be a significant symptom associated with CMT and, as a result, no studies have investigated the pathophysiology underlying neuropathic pain in this disorder. Thus, the first animal model of neuropathic pain was developed by our laboratory using an adenovirus vector system to study neuropathic pain in CMT. To this end, glycyl-tRNA synthetase (GARS) fusion proteins with a FLAG-tag (wild type [WT], L129P and G240R mutants) were expressed in spinal cord and dorsal root ganglion (DRG) neurons using adenovirus vectors. It is known that GARS mutants induce GARS axonopathies, including CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V). Additionally, the morphological phenotypes of neuropathic pain in this animal model of GARS-induced pain were assessed using several possible markers of pain (Iba1, pERK1/2) or a marker of injured neurons (ATF3). These results suggest that this animal model of CMT using an adenovirus may provide information regarding CMT as well as a useful strategy for the treatment of neuropathic pain.

  17. 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.

  18. Radix Astragali-Based Chinese Herbal Medicine for Oxaliplatin-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis

    PubMed Central

    2016-01-01

    Background. Treatment of chemotherapy-induced peripheral neuropathy (CIPN) remains a big challenge for oncologists. The aim of this study is to evaluate the effects of Radix Astragali- (RA-) based Chinese herbal medicine in the prevention and treatment of oxaliplatin-induced peripheral neuropathy, including the incidence and grading of neurotoxicity, effective percentage, and nerve conduction velocity. Methods. All randomized controlled trials (RCTs) were found using PubMed, Cochrane, Springer, China National Knowledge Infrastructure (CNKI), and Wanfang Database of China Science Periodical Database (CSPD) by keyword search. Meta-analysis was conducted using RevMan 5.0. Results. A total of 1552 participants were included in 24 trials. Meta-analysis showed the incidence of all-grade neurotoxicity was significantly lower in experimental groups and high-grade neurotoxicity was also significantly less. Effective percentage was significantly higher and sensory nerve conduction velocity was improved significantly, but changes in motor nerve conduction velocity were not statistically significant. No adverse events associated with RA-based intervention were reported. Conclusion. RA-based intervention may be beneficial in relieving oxaliplatin-induced peripheral neuropathy. However, more double-blind, multicenter, large-scale RCTs are needed to support this theory. Trial Registration. PROSPERO International prospective register of systematic reviews has registration number  CRD42015019903. PMID:27795728

  19. 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

  20. JZL184 is anti-hyperalgesic in a murine model of cisplatin-induced peripheral neuropathy

    PubMed Central

    Khasabova Iryna, A; Yao, Xu; Paz, Justin; Lewandowski Cutler, T; Lindberg Amy, E; Coicou, Lia; Burlakova, Natasha; Simone Don, A; Seybold Virginia, S

    2014-01-01

    Cisplatin has been used effectively to treat a variety of cancers but its use is limited by the development of painful peripheral neuropathy. Because the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG) is anti-hyperalgesic in several preclinical models of chronic pain, the anti-hyperalgesic effect of JZL184, an inhibitor of 2-AG hydrolysis, was tested in a murine model of cisplatin-induced hyperalgesia. Systemic injection of cisplatin (1 mg/kg) produced mechanical hyperalgesia when administered daily for 7 days. Daily peripheral administration of a low dose of JZL184 in conjunction with cisplatin blocked the expression of mechanical hyperalgesia. Acute injection of a cannabinoid (CB)-1 but not a CB2 receptor antagonist reversed the anti-hyperalgesic effect of JZL184 indicating that downstream activation of CB1 receptors suppressed the expression of mechanical hyperalgesia. Components of endocannabinoid signaling in plantar hind paw skin and lumbar dorsal root ganglia (DRGs) were altered by treatments with cisplatin and JZL184. Treatment with cisplatin alone reduced levels of 2-AG and AEA in skin and DRGs as well as CB2 receptor protein in skin. Combining treatment of JZL184 with cisplatin increased 2-AG in DRGs compared to cisplatin alone but had no effect on the amount of 2-AG in skin. Evidence that JZL184 decreased the uptake of [3H]AEA into primary cultures of DRGs at a concentration that also inhibited the enzyme fatty acid amide hydrolase, in conjunction with data that 2-AG mimicked the effect of JZL184 on [3H]AEA uptake support the conclusion that AEA most likely mediates the anti-hyperalgesic effect of JZL184 in this model. PMID:25304184

  1. Efficacy of Contact Needle Therapy for Chemotherapy-Induced Peripheral Neuropathy

    PubMed Central

    Ogawa, Masao; Nishijima, Koji; Tsuda, Masaki; Nishimura, Genichi

    2013-01-01

    Cancer chemotherapy-induced peripheral neuropathy (CIPN) often results in discontinuation of treatment with potentially useful anticancer drugs and may deteriorate the patient's quality of life. This study investigated the effect of contact needle therapy (CNT) on CIPN caused by responsible chemotherapeutic agents as taxanes and oxaliplatin. Six patients with CIPN were treated with CNT. The severity of CIPN was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4 and FACT/GOG-Ntx before and after CNT. After the treatment, all of the patients showed some improvement. Four patients showed apparent improvement in breakthrough pain. One of the cases had difficulty in walking because of CIPN in lower extremities, but after 2 times of CNT, he could walk without pain and could continue the chemotherapy. Although its putative mechanisms remain elusive, CNT has strong potential as an adjunctive therapy in CIPN. Well-designed clinical trials with adequate sample size and power are necessary to confirm the findings of this study. PMID:23762168

  2. 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

  3. Peripheral neuropathy in Parkinson's disease: levodopa exposure and implications for duodenal delivery.

    PubMed

    Müller, Thomas; van Laar, Teus; Cornblath, David R; Odin, Per; Klostermann, Fabian; Grandas, Francisco J; Ebersbach, Georg; Urban, Peter P; Valldeoriola, Francesc; Antonini, Angelo

    2013-05-01

    In advanced Parkinson's disease (PD) patients, continuous intra-duodenal infusion of levodopa/carbidopa intestinal gel (LCIG) is an established approach in the management of motor complications that cannot be further improved by conventional oral therapy. In general, tolerability of LCIG has resembled that of oral dopaminergic therapy; however, cases of symptomatic peripheral neuropathy (PN), sometimes severe, have been reported in patients receiving LCIG. Cases are generally a sensorimotor polyneuropathy with both subacute and chronic onsets, often associated with vitamin B12 and/or B6 deficiency. Rare cases clinically resemble Guillain-Barré syndrome. In the absence of prospectively collected data on possible associations between LCIG and PN, it is prudent to explore potential mechanisms that may explain a possible relationship. The PN may be linked to use of high-dose levodopa, promoting high levels of homocysteine and methylmalonic acid or reduced absorption of vitamins essential for homocysteine metabolism. Cases of LCIG-associated PN often have responded to vitamin supplementation without need for LCIG cessation, although LCIG cessation is sometimes necessary. It may be advisable to monitor vitamin B12/B6 status before and after patients start LCIG and be vigilant for signs of PN. Prospective, large-scale, long-term studies are needed to clarify whether vitamin supplementation and routine use of a catechol-O-methyltransferase inhibitor may help prevent PN in LCIG recipients and whether these measures should be routine practice in patients with PD on high-dose oral levodopa. PMID:23453891

  4. Falls and Balance Impairments in Older Adults with Type 2 Diabetes: Thinking Beyond Diabetic Peripheral Neuropathy.

    PubMed

    Hewston, Patricia; Deshpande, Nandini

    2016-02-01

    Older adults with type 2 diabetes have significantly higher incidence of falls than those without type 2 diabetes. The devastating consequences of falls include declines in mobility, activity avoidance, institutionalization and mortality. One of the most commonly identified risk factors associated with falls is impaired balance. Balance impairments and subsequent increased fall risk in older adults with type 2 diabetes are most commonly associated with diabetic peripheral neuropathy (DPN). Consequently, DPN has been the central focus of falls prevention research and interventions for older adults with type 2 diabetes. However, isolated studies have identified adults with type 2 diabetes without overt complications of DPN to also be at increased fall risk. It is known that the ability to maintain balance is a complex skill that requires the integration of multiple sensorimotor and cognitive processes. Emerging evidence suggests that diabetes-related subtle declines in sensory functions (somatosensory, visual and vestibular), metabolic muscle function and executive functions may also contribute to increased fall risk in older adults with type 2 diabetes. Knowledge of these type 2 diabetes-related sensorimotor and cognitive deficits may help to broaden approaches to falls prevention in older adults with type 2 diabetes. Therefore, the purpose of this mini review is to describe the impact of type 2 diabetes on sensorimotor and cognitive systems that may contribute to increased fall risk in older adults with type 2 diabetes.

  5. Peripheral neuropathy in the Twitcher mutant. A new experimental model of endoneurial edema.

    PubMed

    Powell, H C; Knobler, R L; Myers, R R

    1983-07-01

    The Twitcher mouse (Twi/Twi) is a recently identified mutant experimental model for human globoid leukodystrophy. Affected mice develop neurologic abnormalities with demyelination of white matter and peripheral nerve due to an inherited enzyme deficiency. The neuropathy has unusual pathologic features:severe interstitial edema and infiltration by eosinophils. To investigate its pathogenesis and to identify the mechanism of demyelination, we studied vascular permeability and measured endoneurial fluid pressure. Significantly increased endoneurial fluid pressure was detected in clinically affected animals (average, 6.4 cm H2O) versus controls (1.7 cm H2O), and these data are the first measurements of EFP to be reported in mice. Increased vascular permeability to horseradish peroxidase was visualized by electron microscopy with leakage of horseradish peroxidase between endothelial cells and flooding of the endoneurial interstitium. Numerous eosinophils were present in the interstitium, as well as some polymorphonuclear cells, occasional erythrocytes, and degranulating mast cells. Abnormalities of nerve fibers included swelling of Schwann cells with intracytoplasmic inclusions, demyelination, and remyelination. As well as being a model for globoid leukodystrophy, the Twitcher is the first spontaneously occurring experimental model for endoneurial edema and increased endoneurial fluid pressure.

  6. Experimental alcohol-related peripheral neuropathy: role of insulin/IGF resistance.

    PubMed

    Nguyen, Van Anh; Le, Tran; Tong, Ming; Mellion, Michelle; Gilchrist, James; de la Monte, Suzanne M

    2012-08-01

    The mechanisms of alcohol-related peripheral neuropathy (ALPN) are poorly understood. We hypothesize that, like alcohol-related liver and brain degeneration, ALPN may be mediated by combined effects of insulin/IGF resistance and oxidative stress. Adult male Long Evans rats were chronically pair-fed with diets containing 0% or 37% ethanol (caloric), and subjected to nerve conduction studies. Chronic ethanol feeding slowed nerve conduction in the tibial (p = 0.0021) motor nerve, and not plantar sensory nerve, but it did not affect amplitude. Histological studies of the sciatic nerve revealed reduced nerve fiber diameters with increased regenerative sprouts, and denervation myopathy in ethanol-fed rats. qRT-PCR analysis demonstrated reduced mRNA levels of insulin, IGF-1, and IGF-2 polypeptides, IGF-1 receptor, and IRS2, and ELISAs revealed reduced immunoreactivity for insulin and IGF-1 receptors, IRS-1, IRS-4, myelin-associated glycoprotein, and tau in sciatic nerves of ethanol-fed rats (all p < 0.05 or better). The findings suggest that ALPN is characterized by (1) slowed conduction velocity with demyelination, and a small component of axonal degeneration; (2) impaired trophic factor signaling due to insulin and IGF resistance; and (3) degeneration of myelin and axonal cytoskeletal proteins. Therefore, ALPN is likely mediated by molecular and signal transduction abnormalities similar to those identified in alcoholic liver and brain degeneration.

  7. 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

  8. Male accessory gland inflammation prevalence in type 2 diabetic patients with symptoms possibly reflecting autonomic neuropathy

    PubMed Central

    Condorelli, Rosita A; Vicari, Enzo; Calogero, Aldo E; La Vignera, Sandro

    2014-01-01

    Male accessory gland inflammation or infection (MAGI) is a potentially underdiagnosed complication of type 2 diabetes (DM2); specifically, we reported in a recent study that the frequency of MAGI was 43% among DM2 patients. In previous studies, we have demonstrated that diabetic autonomic neuropathy (DAN) is associated with a peculiar ultrasound characterization of the seminal vesicles (SVs) in DM2 patients. The aim of the present study was to evaluate the frequency of MAGI in two different categories of DM2 patients (i.e. patients with and without symptoms that possibly reflect DAN) and the respective ultrasound characterizations. Sixty DM2 patients with a mean (± s.e.m.) age of 42.0 ± 6.0 years (range: 34–47 years) were classified according to the presence or the absence of symptoms that could possibly reflect DAN (group A: DM2 with symptoms possibly reflecting DAN, n = 28 patients and group B: DM2 without symptoms possibly reflecting DAN, n = 32 patients). The patients in Group A exhibited a significantly higher frequency of MAGI compared with those in group B patients (P < 0.05); moreover, the Group A patients exhibited a significantly higher frequency of ultrasound signs suggestive of vesiculitis (P < 0.05). Finally, the concentrations of lymphocytes but not the concentrations of the leukocytes in the semen were significantly higher (P < 0.05) in group A compared with group B. PMID:24799635

  9. 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

  10. Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial

    PubMed Central

    2012-01-01

    Background Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. Methods This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN). Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score". Results Twenty one patients (70%) of the group taking omega-3 fatty acid supplement (n = 30) did not develop PN while it was 40.7%( 11 patients) in the placebo group(n = 27). A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88), p = 0.029). There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (−2.06 -0.02), p = 0.054). Conclusions Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients’ quality of life. Trial registration This trial was registered at ClinicalTrials.gov (NCT01049295) PMID:22894640

  11. Peripheral neuropathy in hepatitis C virus infection with and without cryoglobulinaemia

    PubMed Central

    Nemni, R; Sanvito, L; Quattrini, A; Santuccio, G; Camerlingo, M; Canal, N

    2003-01-01

    Objectives: Hepatitis C virus (HCV) infection is often associated with cryoglobulinaemia (CG). Peripheral neuropathy (PN) is a comparatively common complication of CG associated with HCV infection and it is thought to be attributable to nerve ischaemia. Only few HCV CG patients with PN have been reported. The recent finding of HCV RNA in nerve biopsy specimens has suggested a possible direct role of HCV in the pathogenesis of PN. The authors studied 51 HCV patients to determine the prevalence of CG and to clarify the possible mechanism by which HCV determines the PN. Methods: All the patients were studied clinically, by laboratory tests and electrophysiologically. Twenty eight patients underwent sural nerve biopsy where both morphological and morphometric evaluation of the biopsy specimen was performed, as well as statistical analysis. Results: CG was found in 40 of 51 cases (78%). Polyneuropathy was significantly prevalent in CG+ patients compared with CG- (18 of 40 compared with 1 of 11 patients; p=0.01). HCV CG- patients more frequently developed well defined mononeuropathy or multiple neuropathy when compared with HCV CG+ (10 of 11 compared with 22 of 40; p<0.03). HCV CG+ patients showed significantly higher proportion of rheumatoid factor positivity (p<0.001) and low C4 levels (p=0.001). Nerve biopsy was performed in 25 of 40 HCV CG+ patients and in 3 of 11 HCV CG- patients: epineurial vasculitis was present in 8 of 25 HCV CG+ (32%) and in 2 of 3 HCV CG-. Differential fascicular loss of axons was found in 10 of 25 CG+ (40%) and 1 of 3 CG-, signs of both demyelination and axonal degeneration were present in 7 of 25 CG+ (28%). No significant difference was found in neuropathological features, while histometrical analysis disclosed more severe involvement in CG+ patients. Conclusions: These findings suggest that the presence of CG is a negative predictive factor for the associated PN. Morphological findings in the sural nerve from HCV CG- and CG+ are consistent

  12. 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

  13. An unusual case of peripheral neuropathy possibly due to arsenic toxicity secondary to excessive intake of dietary supplements.

    PubMed

    Barton, Al; McLean, B

    2013-09-01

    A 74-year-old woman presented to the neurology clinic with worsening of her longstanding peripheral neuropathy of unknown cause. There was below knee loss of spinothalamic sensation, reduced joint position of toes, absent below hips vibration sensation and absent ankle jerks. Neurophysiology studies showed further progression of her axonal sensory neuropathy. Urine and blood analysis previously carried out in Australia suggested elevated levels of arsenic. After abstinence from seafood, a random urine sample was collected and this confirmed the elevation in urine arsenic (622.1 nmol/L, reference range <534 nmol/L). The household water was found to be uncontaminated and the patient had no occupational or environmental exposure to arsenic. On questioning the patient admitted to taking fish oils, omega-3 oils and glucosamine sulphate dietary supplements in excess of the recommended dosage. These supplements were identified as possible sources of arsenic and the patient was asked to stop all supplements. One month later the urine arsenic had reduced to 57.5 nmol/L. There was an improvement in patient wellbeing, she no longer required Gabapentin for pain relief and the neurophysiology studies also showed improvement. Clinicians should consider heavy metal toxicity as a cause of peripheral neuropathy of unknown cause. A detailed patient history including all dietary supplements is essential to help elucidate the source of heavy metal toxicity.

  14. Subclinical Peripheral Neuropathy in Patients With Multiple Myeloma Before Chemotherapy Is Correlated With Decreased Fingertip Innervation Density

    PubMed Central

    Kosturakis, Alyssa K.; He, Zijing; Li, Yan; Boyette-Davis, Jessica A.; Shah, Nina; Thomas, Sheeba K.; Zhang, Haijun; Vichaya, Elisabeth G.; Wang, Xin Shelley; Wendelschafer-Crabb, Gwen; Kennedy, William R.; Simone, Donald A.; Cleeland, Charles S.; Dougherty, Patrick M.

    2014-01-01

    Purpose The goal in this study was to determine the incidence of subclinical neuropathy in treatment-naive patients with multiple myeloma (MM) with no history of peripheral neuropathy using quantitative sensory tests (QSTs) and its correlation with innervation density of the extremities using noninvasive laser reflectance confocal microscopy. Patients and Methods QST results were collected for 27 patients with a diagnosis of MM and compared with data collected from 30 age- and sex-matched healthy volunteers. Skin temperature, sensorimotor function (grooved pegboard test), and detection thresholds for temperature, sharpness, and low-threshold mechanical stimuli (von Frey monofilaments and bumps detection test) were measured. Meissner's corpuscle (MC) density in the fingertips was assessed using in vivo laser reflectance confocal microscopy. Results Patients showed a high incidence (> 80%) of ≥ one subclinical QST deficit. These included increased von Frey, bumps, and warmth detection thresholds as compared with healthy volunteers. Patients also showed increases in cold pain, sensorimotor deficits (grooved pegboard test), and higher overall neuropathy scores. MC density was significantly lower in patients than controls and showed significant inverse correlation with bumps detection threshold. Conclusion Patients with MM commonly present with sensory and sensorimotor deficits before undergoing treatment, and these deficits seem to result from disease-related decreases in peripheral innervation density. PMID:25154818

  15. An unusual case of peripheral neuropathy possibly due to arsenic toxicity secondary to excessive intake of dietary supplements.

    PubMed

    Barton, Al; McLean, B

    2013-09-01

    A 74-year-old woman presented to the neurology clinic with worsening of her longstanding peripheral neuropathy of unknown cause. There was below knee loss of spinothalamic sensation, reduced joint position of toes, absent below hips vibration sensation and absent ankle jerks. Neurophysiology studies showed further progression of her axonal sensory neuropathy. Urine and blood analysis previously carried out in Australia suggested elevated levels of arsenic. After abstinence from seafood, a random urine sample was collected and this confirmed the elevation in urine arsenic (622.1 nmol/L, reference range <534 nmol/L). The household water was found to be uncontaminated and the patient had no occupational or environmental exposure to arsenic. On questioning the patient admitted to taking fish oils, omega-3 oils and glucosamine sulphate dietary supplements in excess of the recommended dosage. These supplements were identified as possible sources of arsenic and the patient was asked to stop all supplements. One month later the urine arsenic had reduced to 57.5 nmol/L. There was an improvement in patient wellbeing, she no longer required Gabapentin for pain relief and the neurophysiology studies also showed improvement. Clinicians should consider heavy metal toxicity as a cause of peripheral neuropathy of unknown cause. A detailed patient history including all dietary supplements is essential to help elucidate the source of heavy metal toxicity. PMID:23761379

  16. 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

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

    PubMed

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

    2014-09-01

    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.

  18. 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

  19. Electroacupuncture for thalidomide/bortezomib-induced peripheral neuropathy in multiple myeloma: a feasibility study

    PubMed Central

    2014-01-01

    Background This single-arm study evaluated feasibility, safety, and initial efficacy of electroacupuncture for thalidomide/bortezomib-induced peripheral neuropathy (PN) in cancer patients with multiple myeloma. Methods Patients with neuropathy ≥ grade 2 received 20 acupuncture treatments over 9 weeks. Results For the 19 evaluable patients, Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity (FACT/GOG/NTX) mean (SD) scores improved significantly between baseline and week 13 (20.8 [9.6] vs 13.2 [8.5], p = 0.0002). Moderate effect size differences began on week 4, with the largest effect size differences found at week 9 for FACT/GOG/NTX scores, worst pain in the last 24 hours, and pain severity (Cohen’s d = 1.43, 1.19, and 1.08, respectively) and continuing through week 13 (Cohen’s d = 0.86, 0.88, and 0.90, respectively). From baseline to week 13, additional significant improvements were seen as follows: postural stability (1.0 [0.6] vs 0.8 [0.4], p = 0.02); coin test (10.0 [7.4] vs 5.6 [1.9], p < 0.0001); button test (96.1 [144.4] vs 54.9 [47.3], p < 0.0001); and walking test (21.6 [10.0] vs 17.2 [7.7], p = 0.0003). No significant changes were seen with NCS. Conclusions Acupuncture may help patients experiencing thalidomide- or bortezomib-induced PN. Larger, randomized, clinical trials are needed. Trial registration ClinicalTrials.gov Identifier: NCT00891618. PMID:24886772

  20. Evaluation of Chemotherapy-Induced Peripheral Neuropathy using Current Perception Threshold and Clinical Evaluations

    PubMed Central

    Griffith, Kathleen A.; Couture, Darren J.; Zhu, Shijun; Pandya, Naimish; Johantgen, Mary E.; Cavaletti, Guido; Davenport, Joan M.; Tanguay, Lori J.; Choflet, Amanda; Milliron, Todd; Glass, Erica; Gambill, Nancy; Renn, Cynthia L.; Dorsey, Susan G.

    2014-01-01

    Purpose Chemotherapy-induced peripheral neuropathy (CIPN) is increasing with introduction of new and combination cancer pharmacotherapies. This study evaluated associations between clinical and self-report measurements and current perception threshold (CPT), a neuroselective measure of sensory nerve function that may detect asymptomatic CIPN damage. Methods Data for this secondary analysis were from a prospective, observational study using CPT to evaluate CIPN. Bivariate mixed models, accounting for the intra-class correlation between repeated patient assessments, were used to assess the relationship between CPT at each frequency (5Hz, 250Hz and 2000 Hz) and each subjective measure (Neuropathic Pain Scale, FACT-GOGntx) and objective measurement (quantitative sensory testing, deep tendon reflexes, grip strength). Results A total of 29 chemotherapy-naïve subjects with various cancer types had a mean age of 56.7 (SD 10.4); 9 subjects developed CIPN grade > 1 using NCI CTC-AE criteria. Cold detection thresholds were inversely associated with CPT 5 [b(95% CI) =−2.5(−4.5, −0.5)] and CPT 2000 [−7.5(−11.8, −3.3)] frequencies. FACT GOG-ntx quality of life (QoL) scale and neurotoxicity and function subscales were inversely associated with CPT 2000 [−1.8 (−3.5, −0.05), −2.2 (−4.2, −0.2), and −5.4(−9.8, −0.9), respectively], indicating worsening QoL, impairment, and function as hypoesthesia increases. Conclusions CPT 2000 may identify impending worsening of patient-reported outcomes, such as QoL. PMID:24362842

  1. 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

  2. Multi-joint foot kinetics during walking in people with Diabetes Mellitus and peripheral neuropathy.

    PubMed

    DiLiberto, Frank E; Tome, Josh; Baumhauer, Judith F; Quinn, Jill R; Houck, Jeff; Nawoczenski, Deborah A

    2015-10-15

    Neuropathic tissue changes can alter muscle function and are a primary reason for foot pathologies in people with Diabetes Mellitus and peripheral neuropathy (DMPN). Understanding of foot kinetics in people with DMPN is derived from single-segment foot modeling approaches. This approach, however, does not provide insight into midfoot power and work. Gaining an understanding of midfoot kinetics in people with DMPN prior to deformity or ulceration may help link foot biomechanics to anticipated pathologies in the midfoot and forefoot. The purpose of this study was to evaluate midfoot (MF) and rearfoot (RF) power and work in people with DMPN and a healthy matched control group. Thirty people participated (15 DMPN and 15 Controls). An electro-magnetic tracking system and force plate were used to record multi-segment foot kinematics and ground reaction forces during walking. MF and RF power, work, and negative work ratios were calculated and compared between groups. Findings demonstrated that the DMPN group had greater negative peak power and reduced positive peak power at the MF and RF (all p≤0.05). DMPN group negative work ratios were also greater at the MF and RF [Mean difference MF: 9.9%; p=0.24 and RF: 18.8%; p<0.01]. In people with DMPN, the greater proportion of negative work may negatively affect foot structures during forward propulsion, when positive work and foot stability should predominate. Further study is recommended to determine how both MF and RF kinetics influence the development of deformity and ulceration in people with DMPN.

  3. 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

  4. Hemorheologic and hemostatic changes in long-standing insulin-dependent (type I) diabetic patients with peripheral and autonomic cardiovascular neuropathy.

    PubMed

    Solerte, S B; Fioravanti, M; Schifino, N; Patti, A L; Gamba, G; Ferrari, E

    1988-01-01

    Diabetic microangiopathy may be associated with the pathogenesis and progression of autonomic and peripheral neuropathy. In 17 long-standing type I diabetic patients with peripheral and autonomic cardiovascular neuropathy, several hemorheological and hemostatic alterations were found compared to 13 matched type I patients without neuropathy. In particular, increased plasma von Willebrand factor antigen (p less than 0.001), fibronectin (p less than 0.001) and fibrinogen (p less than 0.001) levels were demonstrated in neuropathic in comparison with non-neuropathic diabetic patients. Moreover negative correlations between these parameters and both motor and sensitive conduction velocity of median, sural and peroneal nerves were observed in diabetic patients with neuropathy. Higher blood viscosity (p less than 0.05 at shear-rate of 450 and 225 s-1; p less than 0.01 at 90 s-1; p less than 0.001 at 4.5 and 2.25 s-1), plasma viscosity (p less than 0.001) and lower erythrocyte filtrability (p less than 0.001) were also found in neuropathic compared to non-neuropathic diabetics. Increased prevalence of retinopathy (p less than 0.01) and nephropathy (p less than 0.001) was finally reported in patients with autonomic and peripheral neuropathy. Microvascular disease may be involved in the development of neuropathy in long-term type I diabetes mellitus.

  5. The Inferior Whorl For Detecting Diabetic Peripheral Neuropathy Using Corneal Confocal Microscopy

    PubMed Central

    Petropoulos, Ioannis N.; Ferdousi, Maryam; Marshall, Andrew; Alam, Uazman; Ponirakis, Georgios; Azmi, Shazli; Fadavi, Hassan; Efron, Nathan; Tavakoli, Mitra; Malik, Rayaz A.

    2015-01-01

    Purpose. In vivo corneal confocal microscopy (CCM) is increasingly used as a surrogate endpoint in studies of diabetic polyneuropathy (DPN). However, it is not clear whether imaging the central cornea provides optimal diagnostic utility for DPN. Therefore, we compared nerve morphology in the central cornea and the inferior whorl, a more distal and densely innervated area located inferior and nasal to the central cornea. Methods. A total of 53 subjects with type 1/type 2 diabetes and 15 age-matched control subjects underwent detailed assessment of neuropathic symptoms (NPS), deficits (neuropathy disability score [NDS]), quantitative sensory testing (vibration perception threshold [VPT], cold and warm threshold [CT/WT], and cold- and heat-induced pain [CIP/HIP]), and electrophysiology (sural and peroneal nerve conduction velocity [SSNCV/PMNCV], and sural and peroneal nerve amplitude [SSNA/PMNA]) to diagnose patients with (DPN+) and without (DPN−) neuropathy. Corneal nerve fiber density (CNFD) and length (CNFL) in the central cornea, and inferior whorl length (IWL) were quantified. Results. Comparing control subjects to DPN− and DPN+ patients, there was a significant increase in NDS (0 vs. 2.6 ± 2.3 vs. 3.3 ± 2.7, P < 0.01), VPT (V; 5.4 ± 3.0 vs. 10.6 ± 10.3 vs. 17.7 ± 11.8, P < 0.01), WT (°C; 37.7 ± 3.5 vs. 39.1 ± 5.1 vs. 41.7 ± 4.7, P < 0.05), and a significant decrease in SSNCV (m/s; 50.2 ± 5.4 vs. 48.4 ± 5.0 vs. 39.5 ± 10.6, P < 0.05), CNFD (fibers/mm2; 37.8 ± 4.9 vs. 29.7 ± 7.7 vs. 27.1 ± 9.9, P < 0.01), CNFL (mm/mm2; 27.5 ± 3.6 vs. 24.4 ± 7.8 vs. 20.7 ± 7.1, P < 0.01), and IWL (mm/mm2; 35.1 ± 6.5 vs. 26.2 ± 10.5 vs. 23.6 ± 11.4, P < 0.05). For the diagnosis of DPN, CNFD, CNFL, and IWL achieved an area under the curve (AUC) of 0.75, 0.74, and 0.70, respectively, and a combination of IWL-CNFD achieved an AUC of 0.76. Conclusions. The parameters of CNFD, CNFL, and IWL have a comparable ability to diagnose patients with DPN. However, IWL

  6. Study of Vitamin B12 deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus

    PubMed Central

    Roy, Rudra Prasad; Ghosh, Kaushik; Ghosh, Manas; Acharyya, Amitava; Bhattacharya, Ambarish; Pal, Mrinal; Chakraborty, Sisir; Sengupta, Nilanjan

    2016-01-01

    Background: Long-term therapy with metformin was shown to decrease the Vitamin B12 level and manifested as peripheral neuropathy. Aim: The aim of this study is to define the prevalence of Vitamin B12 deficiency in early Type 2 diabetic patients (duration ≤5 years or drug treatment ≤3 years) and the relationship among metformin exposure and levels of cobalamin (Cbl), folic acid, and homocysteine (Hcy) with severity of peripheral neuropathy. Methodology: This is a cross-sectional study involving randomly selected ninety patients (male 56, female 34) between age groups of 35 and 70 years, comparing those who had received >6 months of metformin (Group A) (n = 35) with those without metformin (Group B) (n = 35) and patients taking metformin with other oral hypoglycemic agent (Group C) (n = 20). Comparisons were made clinically, biochemically (serum Cbl, fasting Hcy, and folic acid), and with electrophysiological measures (nerve conduction studies of all four limbs). Comorbidities contributing to neuropathy were excluded from the study. Results: Group A patients (54.28%) were prone to develop peripheral neuropathy comparing Group B (28.57%) and Group C (35%). There was significantly low plasma level of Cbl in Group A (mean 306.314 pg/ml) than in Group B (mean 627.543 pg/ml) and Group C (mean 419.920 pg/ml). There was insignificant low-level plasma folic acid in Group A (16.47 ng/ml) than in Group B (16.81 ng/ml) and Group C (22.50 ng/ml). There was significantly high level of Hcy in Group A (mean 17.35 µmol/L) and Group C (mean 16.99 µmol/L) than in Group B (mean 13.22 µmol/L). Metformin users even for 2 years showed evidence of neuropathy on nerve conduction velocity though their body mass index and postprandial blood sugar were maintained. There was significant difference in between groups regarding plasma Cbl, folic acid, and Hcy level as significance level <0.05 in all three groups (F [2, 87] = 28.1, P = 0.000), (F [2, 87] = 7.43, P = 0.001), (F [2, 87] = 9

  7. 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

  8. 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

  9. Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia

    PubMed Central

    Diouf, Barthelemy; Crews, Kristine R.; Lew, Glen; Pei, Deqing; Cheng, Cheng; Bao, Ju; Zheng, Jie J.; Yang, Wenjian; Fan, Yiping; Wheeler, Heather E.; Wing, Claudia; Delaney, Shannon M.; Komatsu, Masaaki; Paugh, Steven W.; McCorkle, Joseph Robert; Lu, Xiaomin; Winick, Naomi J.; Carroll, William L.; Loh, Mignon L.; Hunger, Stephen P.; Devidas, Meenakshi; Pui, Ching-Hon; Dolan, M. Eileen; Relling, Mary V.; Evans, William E.

    2015-01-01

    Importance With cure rates of childhood acute lymphoblastic leukemia (ALL) exceeding 85%, there is compelling need to mitigate treatment toxicities that can compromise quality of life. Peripheral neuropathy is the major dose-limiting toxicity of the microtubule inhibitor vincristine, an anticancer agent given to every child with ALL. Objective Identify genetic germline variants associated with the occurrence or severity of vincristine-induced peripheral neuropathy in children with ALL. Design, Setting and Participants All patients had been enrolled in one of two prospective clinical trials for childhood ALL that included treatment with 36–39 doses of vincristine. Genome-wide single nucleotide polymorphism (SNP) analysis and vincristine-induced peripheral neuropathy were assessed in all patients from whom DNA was available (n=321 patients); 222 patients (median age at 6.0 years, range 0.1–18.8 years) enrolled between 1994–1998 on the St. Jude Children’s Research Hospital protocol Total XIIIB (St. Jude cohort) with toxicity followed through January 2001, and 99 patients (median age 11.4 years, range 3.0–23.8 years) enrolled between 2007–2010 on the Children’s Oncology Group protocol AALL0433 (COG cohort) with toxicity followed through May 2011. Human leukemia cells and induced pluripotent stem cell neurons were used to assess the effects of lower CEP72 expression on vincristine sensitivity. Exposures Treatment with vincristine at a dosage of 1.5 or 2.0 mg/m2 as a component of protocol directed chemotherapy for childhood ALL. Main Outcomes and Measures Vincristine-induced peripheral neuropathy was assessed at each clinic visit using the National Cancer Institute Common Terminology Criteria for Adverse Events and prospectively graded as mild (grade 1), moderate (grade 2), serious/disabling (grade 3), or life-threatening (grade 4). Results Grade 2–4 vincristine-induced neuropathy during continuation therapy occurred in 28.8% of patients (n=64 of 222) in

  10. Identification of two novel KIF5A mutations in hereditary spastic paraplegia associated with mild peripheral neuropathy.

    PubMed

    López, Eva; Casasnovas, Carlos; Giménez, Javier; Santamaría, Raúl; Terrazas, Jesús M; Volpini, Víctor

    2015-11-15

    Spastic paraplegia type 10 (SPG10) is a rare form of autosomal dominant hereditary spastic paraplegia (AD-HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy-chain involved in axonal transport. KIF5A mutations have been associated with a wide clinical spectrum, ranging from pure HSP to isolated peripheral nerve involvement or complicated HSP phenotypes. Most KIF5A mutations are clustered in the motor domain of the protein that is necessary for microtubule interaction. Here we describe two Spanish families with an adult onset complicated AD-HSP in which neurological studies revealed a mild sensory neuropathy. Intention tremor was also present in both families. Molecular genetic analysis identified two novel mutations c.773 C>T and c.833 C>T in the KIF5A gene resulting in the P258L and P278L substitutions respectively. Both were located in the highly conserved kinesin motor domain of the protein which has previously been identified as a hot spot for KIF5A mutations. This study adds to the evidence associating the known occurrence of mild peripheral neuropathy in the adult onset SPG10 type of AD-HSP. PMID:26403765

  11. Identification of two novel KIF5A mutations in hereditary spastic paraplegia associated with mild peripheral neuropathy.

    PubMed

    López, Eva; Casasnovas, Carlos; Giménez, Javier; Santamaría, Raúl; Terrazas, Jesús M; Volpini, Víctor

    2015-11-15

    Spastic paraplegia type 10 (SPG10) is a rare form of autosomal dominant hereditary spastic paraplegia (AD-HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy-chain involved in axonal transport. KIF5A mutations have been associated with a wide clinical spectrum, ranging from pure HSP to isolated peripheral nerve involvement or complicated HSP phenotypes. Most KIF5A mutations are clustered in the motor domain of the protein that is necessary for microtubule interaction. Here we describe two Spanish families with an adult onset complicated AD-HSP in which neurological studies revealed a mild sensory neuropathy. Intention tremor was also present in both families. Molecular genetic analysis identified two novel mutations c.773 C>T and c.833 C>T in the KIF5A gene resulting in the P258L and P278L substitutions respectively. Both were located in the highly conserved kinesin motor domain of the protein which has previously been identified as a hot spot for KIF5A mutations. This study adds to the evidence associating the known occurrence of mild peripheral neuropathy in the adult onset SPG10 type of AD-HSP.

  12. Peripheral neuropathy: the importance of history and examination for correct diagnosis.

    PubMed

    Kelly, John J

    2005-01-01

    A 48-year-old woman presented to the emergency department with hematemesis and a 6-month history of unsteady gait and falls due to tripping. Because of a history of alcohol abuse, the initial diagnosis was upper gastrointestinal bleeding secondary to alcoholic gastritis or gastric ulcer, with the neuropathy likely due to alcoholism or chronic inflammatory demyelinating polyneuropathy. After further neurological examination and careful review of nerve conduction studies, however, an inherited neuropathy was suspected. Despite denial by the patient and her daughter of a family history of neuropathy, both had a pes cavus deformity with muscle atrophy and partial foot drop gait. Subsequent testing of the daughter revealed the same nerve conduction findings as the patient's. Genetic testing showed that both women had the myelin PMP22 repeat defect characteristic of Charcot-Marie-Tooth disease. Endoscopy revealed that the patient had Osler-Weber-Rendu disease, which accounted for the hematemesis.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. The Positive Effects of One-Hour Intravenous Administration of Bortezomib on Peripheral Neuropathy in Multiple Myeloma Patients

    PubMed Central

    Jung, Joo Young; Kim, Ho Young; Han, Boram; Choi, Dae Ro; Zang, Dae Young; Kim, Hyo Jung

    2014-01-01

    Bortezomib-induced peripheral neuropathy (BiPN) in multiple myeloma (MM) patients is a common and serious side effect. Currently, it has been reported that subcutaneous (SC) administration of bortezomib decreases the incidence of BiPN as compared to standard intravenous (IV) bolus injection without any differences in efficacy. However, there are reports of severe injection site reaction following SC administration of bortezomib. The aim of this study was to evaluate the response rate and incidence of BiPN following one-hour IV infusion of bortezomib. The data was retrospectively collected from MM patients who had been treated with IV administration of bortezomib for one hour. Twenty-three patients were evaluated (median age 72 years, 13 males). The median number of treatment cycles was 5 (range 2–10). The cumulative bortezomib dose was 26.0 mg/m2 (14.3–66.3) and percent of actual per expected cumulative dose was 90% (50–100). The overall response (complete response plus partial response) rate was 65%. The incidence of BiPN was 57% (n = 13) and incidence of severe neuropathy was 4% (n = 1). One-hour IV infusion of bortezomib was an effective regimen for MM with reduced incidence of severe BiPN. This route of administration of bortezomib could be an alternative mode of delivery for patients with severe injection site reactions following SC administration. PMID:24995276

  19. Histopathological and behavioral evaluations of the effects of crocin, safranal and insulin on diabetic peripheral neuropathy in rats

    PubMed Central

    Farshid, Amir Abbas; Tamaddonfard, Esmaeal

    2015-01-01

    Objectives: Crocin and safranal, the major constituents of saffron, exert neuroprotective effects. In the present study, we investigated the effects of crocin and safranal (alone or in combination with insulin) on peripheral neuropathy in diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (i.p.) injection of 60 mg/kg of streptozotocin (STZ) and confirmed by blood glucose level higher than 250 mg/dl. After confirmation of diabetes, crocin (30 mg/kg, i.p.), safranal (1 mg/kg, i.p.) (alone or in combination with insulin) and insulin (5 IU/kg, s.c.) were administered for eight weeks. Neuropathic pain was evaluated using acetone drop test. Histopathological changes of sciatic nerve were evaluated using light microscope. Blood glucose levels and sciatic nerve malondialdehyde (MDA) contents were also measured. Results: STZ caused cold allodynia, edema and degenerative changes of sciatic nerve, hyperglycemia and an elevation of sciatic nerve MDA levels. Crocin, safranal and insulin improved STZ-induced behavioral, histopathological and biochemical changes. Combined treatments produced more documented improving effects. Conclusion: The results of the present study showed neuroprotective effects of crocin, safranal and insulin in a rat model of diabetic neuropathy. In addition, crocin and safranal enhanced the neuroprotective effect of insulin. The neuroprotective effects of theses chemical compounds could be associated with their anti-hyperglycemic and antioxidant properties. PMID:26468467

  20. Peripheral neuropathy as the presenting feature of tyrosinaemia type I and effectively treated with an inhibitor of 4-hydroxyphenylpyruvate dioxygenase.

    PubMed

    Gibbs, T C; Payan, J; Brett, E M; Lindstedt, S; Holme, E; Clayton, P T

    1993-10-01

    A 21 month old girl presented with a short history of frequent falls and a right sided foot drop. She went on to suffer recurrent episodes of distal weakness in her arms and legs with hyporeflexia. Electrophysiological studies were consistent with inflammatory demyelinating polyradiculoneuropathy (IDP) and treatment with corticosteroids appeared to lead to an improvement. However, the development of hypertension, evidence of tubulopathy, and hepatomegaly led to re-evaluation. A diagnosis of type I tyrosinaemia was made, based on increased urinary excretion of succinylacetone and decreased activity of fumarylacetoacetase in her cultured skin fibroblasts. A low tyrosine diet did not prevent life-threatening exacerbations of neuropathy but intravenous haemarginate appeared to aid her recovery from one exacerbation. An immediate improvement in strength was seen after starting treatment with 2-(2-nitro-4-trifluoro-methyl-benzoyl)-1,3-cyclohexanedione (NTBC), an inhibitor of 4-hydroxy-phenylpyruvate dioxygenase. A liver transplant was performed but the patient died of immediate postoperative complications. Tyrosinaemia needs to be considered in a child with recurrent peripheral neuropathy because (i) the signs of liver disease and renal tubular dysfunction may be subtle; (ii) acute exacerbations may be life threatening; (iii) specific forms of treatment are available.

  1. Monocyte Traffic, Dorsal Root Ganglion Histopathology, and Loss of Intraepidermal Nerve Fiber Density in SIV Peripheral Neuropathy

    PubMed Central

    Lakritz, Jessica R.; Bodair, Ayman; Shah, Neal; O'Donnell, Ryan; Polydefkis, Michael J.; Miller, Andrew D.; Burdo, Tricia H.

    2016-01-01

    HIV-associated sensory neuropathy remains the most common neurological complication of HIV infection and is characterized by dorsal root ganglion (DRG) inflammation and intraepidermal nerve fiber density (IENFD) loss. Chronic peripheral immune cell activation and accumulation may cause damage to the DRG, but has not been fully investigated yet. By using an SIV-infected, CD8-lymphocyte–depleted rhesus macaque model, we defined immune cells surrounding DRG neurons and their role in DRG pathology, measured cell traffic from the bone marrow to the DRGs using 5-bromo-2-deoxyuridine (BrdU) pulse, and serially measured IENFD. We found an increase in CD68+ and CD163+ macrophages in DRGs of SIV-infected animals. MAC387+ recently recruited monocytes/macrophages were increased, along with BrdU+ cells, in the DRGs of SIV-infected macaques. We demonstrated that 78.1% of all BrdU+ cells in DRGs were also MAC387+. The number of BrdU+ monocytes correlated with severe DRG histopathology, which included neuronophagia, neuronal loss, and Nageotte nodules. These data demonstrate that newly recruited MAC387+BrdU+ macrophages may play a significant role in DRG pathogenesis. IENFD decreased early (day 21), consistent with the development of sensory neuropathy in SIV-infected macaques. Decreased IENFD was associated with elevated BrdU+ cells in the DRG. These data suggest that increased recruitment of macrophages to DRG is associated with severe DRG histopathology and IENFD loss. PMID:25956030

  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. 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

  4. 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.

  5. Etodolac, a cyclooxygenase-2 inhibitor, attenuates paclitaxel-induced peripheral neuropathy in a mouse model of mechanical allodynia.

    PubMed

    Ito, Sunao; Tajima, Koyuki; Nogawa, Masaki; Inoue, Naoki; Kyoi, Takashi; Takahashi, Yosuke; Sasagawa, Takahiro; Nakamura, Akio; Kotera, Takashi; Ueda, Makoto; Yamashita, Yasuhiro; Banno, Kouji

    2012-07-01

    The effect of the cyclooxygenase-2 (COX-2) inhibitor etodolac on the mechanical allodynia induced by paclitaxel was investigated in mice and compared with the effects of the nonselective COX inhibitors indomethacin and diclofenac, the selective COX-2 inhibitor celecoxib, the calcium channel α(2)δ subunit inhibitor pregabalin, the sodium channel blocker mexiletine, and the serotonin-norepinephrine reuptake inhibitor duloxetine. The decrease in the paw-withdrawal threshold induced by paclitaxel was reversed by oral administration of etodolac at 10 mg/kg but was not affected by indomethacin, diclofenac, or celecoxib. The antiallodynic effect of etodolac gradually increased during repeated administration, and after 2 weeks the paw-withdrawal threshold at the preadministration point was significantly increased. Pregabalin, duloxetine, and mexiletine also showed an antiallodynic effect in this model. Whereas pregabalin had a preadministration effect similar to that of etodolac during repeated administration, mexiletine or duloxetine had no such effect. There was almost no difference in the distribution of etodolac and diclofenac in nervous tissue, indicating that COX inhibition is unlikely to be involved in the antiallodynic effect of etodolac. Etodolac did not show a neuroprotective effect against morphological transformations such as the axonal degeneration induced by paclitaxel. Instead, etodolac probably acts at the level of functional changes accompanying paclitaxel treatment, such as alterations in the activation state of components of the pain transmission pathway. Our findings suggest that etodolac attenuates paclitaxel-induced peripheral neuropathy by a COX-independent pathway and that it might be useful for the treatment of paclitaxel-induced peripheral neuropathy. PMID:22460833

  6. The Association between Serum Cytokines and Damage to Large and Small Nerve Fibers in Diabetic Peripheral Neuropathy

    PubMed Central

    Magrinelli, Francesca; Briani, Chiara; Romano, Marcello; Ruggero, Susanna; Toffanin, Elisabetta; Triolo, Giuseppa; Peter, George Chummar; Praitano, Marialuigia; Lauriola, Matteo Francesco; Zanette, Giampietro

    2015-01-01

    Diabetic peripheral neuropathy (DPN) is a frequent complication of type 2 diabetes mellitus (DM) and may involve small and large peripheral nerve fibers. Recent evidence suggests a role of cytokines in DPN. The paper is aimed at exploring whether the serum concentration of cytokines is associated with small and large nerve fiber function and with neuropathic pain (NP). We recruited a group of 32 type 2 DM patients who underwent serum cytokines (TNF-α, IL-2, IL-4, IL-6, and IL-10) dosage as well as electrodiagnostic and quantitative sensory testing (QST) assessment to explore damage to large and small nerve fibers. Raised serum levels of IL-6 and IL-10 correlated with markers of large nerve fiber sensory and motor axonal damage. Raised IL-10 serum level was associated with signs of motor nerve demyelination. No differences were found in pain characteristics and electrodiagnostic and QST markers of small nerve fiber function in relation to cytokines serum levels. IL-6 and IL-10 serum levels were associated with large nerve fiber damage but not to small fibers function or NP. IL-6 and IL-10 cytokines might play a role in the pathogenesis of nerve fiber damage or represent a compensatory or neuroprotective mechanism. PMID:25961054

  7. 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

  8. Effects of meditation on pain and quality of life in multiple sclerosis and peripheral neuropathy: a pilot study.

    PubMed

    Tavee, Jinny; Rensel, Mary; Planchon, Sarah M; Butler, Robert S; Stone, Lael

    2011-01-01

    The objective of this study was to determine whether meditation affects pain and quality of life in people with multiple sclerosis (MS) and peripheral neuropathy (PN). A total of 22 patients (10 with MS, 12 with PN) participated in a weekly meditation class over a 2-month period. A total of 18 controls (7 with MS, 11 with PN) received standard care. Primary outcome assessments were based on the 36-item Short Form Health Status Survey (SF-36) and a visual analogue scale (VAS) for pain at baseline and at 2 months. Secondary outcome measures included the Neuropathy Impairment Score (NIS) for PN patients and the Patient-Determined Disease Steps (PDDS) questionnaire and 5-item Modified Fatigue Impact Scale (MFIS-5) for MS patients. After 2 months, study participants who practiced meditation reported an improvement in pain on the VAS (P = .035 combined group), summed physical health scores on the SF-36 (P = .011 MS, P = .014 PN), summed mental health scores (P = .02 combined group), vitality (P = .005 combined group), and physical role (P = .003 combined group). A significant improvement was also observed for bodily pain (P = .031) in MS patients. In contrast, no significant differences before and after the intervention were observed for controls. Regarding the secondary measure of fatigue, improved scores for the cognitive and psychosocial components of the MFIS were noted in MS patients in the intervention group (P = .037, P = .032). No statistically significant changes were observed in the NIS for PN patients or in PDDS scores for MS patients. Meditation may be helpful in reducing pain and improving quality of life in patients with MS and PN. The lack of changes seen in mobility (MS) and sensorimotor deficits (PN) suggests that meditation may not affect the overall clinical course.

  9. 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.

  10. 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

  11. Acetylator phenotype in diabetic neuropathy.

    PubMed

    McLaren, E H; Burden, A C; Moorhead, P J

    1977-07-30

    The proportions of slow and fast acetylators in a group of diabetics with symptomatic peripheral neuropathy were compared with those in a group of diabetics who had had the disease for at least 10 years without developing neuropathy. There was a significantly higher proportion of fast acetylators in the group of diabetics without neuropathy than in those with neuropathy or in the normal population. Hence genetic factors separate from the diabetic diathesis may determine the development of neuropathy in any particular diabetic.

  12. 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...

  13. Mixed or immune complex cryoglobulinaemia and neuropathy

    PubMed Central

    Cream, J. J.; Hern, J. E. C.; Hughes, R. A. C.; Mackenzie, I. C. K.

    1974-01-01

    Three patients with peripheral neuropathy and mixed or immune complex cryoglobulinaemia are reported. The significance of mixed cryoglobulinaemia and the pathogenesis of the peripheral neuropathy are discussed. Images PMID:4360402

  14. 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.

  15. Vitamin E does not decrease the incidence of chemotherapy-induced peripheral neuropathy: a meta-analysis

    PubMed Central

    He, Mei; Liu, Lihua; Huang, Lili

    2016-01-01

    Aim of this study Chemotherapy-induced peripheral neuropathy (CIPN) is a major complication of cancer patients with chemotherapy. Although many interventions have been evaluated in previous studies, findings are controversial. The aim of this meta-analysis is to assess the efficacy of vitamin E supplementation in preventing CIPN. Material and methods The electronic databases MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched from their inception to December 31, 2013 to identify relevant randomised controlled trials. Two reviewers independently scanned and extracted the data of included studies. Review Manager 5.2 was used to analyse data. Results Six articles involving 353 patients were included in meta-analysis. The results showed that vitamin E supplementation did not appear to significantly decrease the incidence of CIPN (relative risk (RR), 0.55; 95% confidence interval (CI), 0.29 to 1.05; p = 0.07), with significant heterogeneity (I2 = 77%). However, Vitamin E supplementation can significantly prevent cisplatin associated neurotoxicity (RR, 0.31; 95%CI, 0.17 to 0.58; p = 0.0002), with no heterogeneity (I2 = 0%). Conclusions Vitamin E administration dose not decrease the incidence of CIPN. However, additional randomised controlled trials using large samples are needed to confirm the role of vitamin E supplementation.

  16. The relationship of glucokinase activator-induced hypoglycemia with arteriopathy, neuronal necrosis, and peripheral neuropathy in nonclinical studies.

    PubMed

    Pettersen, John C; Litchfield, John; Neef, Natasha; Schmidt, Stephen P; Shirai, Norimitsu; Walters, Karen M; Enerson, Bradley E; Chatman, Linda A; Pfefferkorn, Jeffrey A

    2014-06-01

    Glucokinase activators (GKAs) are being developed for the treatment of type 2 diabetes. The toxicity of 4 GKAs (PF-04279405, PF-04651887, piragliatin, and PF-04937319) was assessed in mice, rats, dogs, and/or monkeys. GKAs were administered for 2 to 8 weeks. Standard endpoints, glucose, and insulin were assessed. All compounds produced varying degrees of hypoglycemia in all species. Brain neuronal necrosis and/or peripheral neuropathy were observed with most compounds. These findings are consistent with literature reports linking hypoglycemia with nervous system effects. Arteriopathy, mainly of cardiac vessels, was observed at a low frequency in monkey and/or dog. Arteriopathy occurred only at doses that produced severe and prolonged periods of repeated hypoglycemia. Since this lesion occurred in multiple studies with structurally distinct GKAs, these results suggested arteriopathy was related to GKA pharmacology. The morphological characteristics of the arteriopathy were consistent with that produced by experimental catecholamine administration. We hypothesize that the prolonged periods of hypoglycemia resulted in increased local and/or systemic concentrations of catecholamines via a counterregulatory and/or stress-related mechanism. Alternatively, prolonged hypoglycemia may have resulted in endothelial dysfunction leading to arteriopathy. This risk can be managed in human patients in clinical studies by careful glucose monitoring and intervention to avoid prolonged episodes of hypoglycemia.

  17. 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

  18. 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.

  19. 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

  20. Successful Spinal Cord Stimulator Trial and Permanent Implant in Patient with Diabetic Peripheral Neuropathy on Chronic Dual Antiplatelet Therapy.

    PubMed

    Covert, Brian P; Nobles, Ryan H

    2015-01-01

    The safety of neuraxial anesthetic techniques in the setting of oral and parenteral anticoagulation is an area of growing interest and clinical inquiry as the multitude of anticoagulant medications rapidly increases. Additionally, the indications for spinal cord stimulation therapy are evolving as both technique and technology in the field continue to advance. The estimated incidence of spinal hematoma following epidural injection has been estimated to be 1 in 150,000-200,000. However, there is very little data on the risk of indwelling spinal cord simulation leads and chronic use of anticoagulant medications. We would like to report a recent case for consideration in which a spinal cord stimulator trial was successful and led to permanent spinal cord stimulator implantation in a patient with diabetic peripheral neuropathy taking life-long aspirin and clopidogrel therapy secondary to extensive coronary and carotid atherosclerosis. The report serves as a novel case to encourage exploration into the topic of anticoagulation therapy with indwelling spinal cord stimulator leads. The case brings up a number of critical questions that cannot clearly be answered with the current literature and some interesting topics for discussion including the need for acute systemic anticoagulation in the future for vascular interventions and risk stratification for those patients selected for spinal cord stimulation. PMID:26431144

  1. Vitamin E does not decrease the incidence of chemotherapy-induced peripheral neuropathy: a meta-analysis

    PubMed Central

    He, Mei; Liu, Lihua; Huang, Lili

    2016-01-01

    Aim of this study Chemotherapy-induced peripheral neuropathy (CIPN) is a major complication of cancer patients with chemotherapy. Although many interventions have been evaluated in previous studies, findings are controversial. The aim of this meta-analysis is to assess the efficacy of vitamin E supplementation in preventing CIPN. Material and methods The electronic databases MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched from their inception to December 31, 2013 to identify relevant randomised controlled trials. Two reviewers independently scanned and extracted the data of included studies. Review Manager 5.2 was used to analyse data. Results Six articles involving 353 patients were included in meta-analysis. The results showed that vitamin E supplementation did not appear to significantly decrease the incidence of CIPN (relative risk (RR), 0.55; 95% confidence interval (CI), 0.29 to 1.05; p = 0.07), with significant heterogeneity (I2 = 77%). However, Vitamin E supplementation can significantly prevent cisplatin associated neurotoxicity (RR, 0.31; 95%CI, 0.17 to 0.58; p = 0.0002), with no heterogeneity (I2 = 0%). Conclusions Vitamin E administration dose not decrease the incidence of CIPN. However, additional randomised controlled trials using large samples are needed to confirm the role of vitamin E supplementation. PMID:27647988

  2. BGP-15, a hydroximic acid derivative, protects against cisplatin- or taxol-induced peripheral neuropathy in rats.

    PubMed

    Bárdos, G; Móricz, K; Jaszlits, L; Rabloczky, G; Tory, K; Rácz, I; Bernáth, S; Sümegi, B; Farkas, B; Literáti-Nagy, B; Literáti-Nagy, P

    2003-07-01

    The neuroprotective effect of BGP-15 against peripheral sensory neuropathy was studied in rats that were exposed to short-term cisplatin or taxol administration. The changes of nerve conduction velocity were determined in situ after treating the Wistar rats with BGP-15 (50, 100, and 200 mg/kg po daily doses throughout the experiment), cisplatin (1.5 mg/kg ip daily dose for 5 days), or taxol (5.0 mg/kg ip daily dose every other day in a 10-day interval) alone or giving the test compound in combination with cisplatin or taxol. Electrophysiological recordings were carried out in vivo by stimulating the sciatic nerve at both sciatic notch and ankle site. Neither motor nor sensory nerve conduction velocity was altered by any dose level of BGP-15 tested. Both anticancer drugs decreased the sensory nerve conduction velocity (SNCV). BGP-15 treatment prevented the impairment of SNCV either in part or totally in the cisplatin- or taxol-treated groups. This neuroprotective potential of BGP-15 could be well correlated with its recently described poly(ADP-ribose) polymerase- inhibitory effect and its ability to protect against the damages induced by the increased level of reactive oxygen species in response to anticancer treatment.

  3. Mild peripheral neuropathy but biochemical chromium sufficiency during 16 months of "chromium-free" total parenteral nutrition.

    PubMed

    Kien, C L; Veillon, C; Patterson, K Y; Farrell, P M

    1986-01-01

    A 6-yr, 4-month-old boy was started on total parenteral nutrition (TPN) because of chronic diarrhea. The TPN regimen (3 liter/day) initially included supplemented Cr (3 micrograms/day) in addition to standard components (including FreAmine III). At age 8 yr, 8 months, the serum Cr level was elevated: 3.7 ng/ml (normal 0.03-0.85). A repeat level at the same time by another commercial laboratory was also high (7.0). Cr supplementation was stopped. At age 10 yr, he was noted to have mild peripheral neuropathy although glucose tolerance was excellent (alpha-linolenic acid was undetectable in the plasma). Cr status was reevaluated in a research lab. The serum level was 1.4 ng/ml (normal 0.05-0.4). The urine chromium excretion was 1.27 micrograms/day (normal 0.22). The TPN regimen (unsupplemented with Cr) provided 4 micrograms/day. Normal Cr intake is about 60 micrograms/day with 0.4% absorption (net 0.24 microgram/day). We conclude that Cr contamination of standard PN fluid may prevent biochemical evidence of low Cr status. In addition, alpha-linolenic acid-free parenteral nutrition for 46 months was not associated with clinically significant neurological dysfunction. PMID:3099015

  4. Gait pattern alterations in older adults associated with type 2 diabetes in the absence of peripheral neuropathy--results from the Baltimore Longitudinal Study of Aging.

    PubMed

    Ko, Seung-uk; Stenholm, Sari; Chia, Chee W; Simonsick, Eleanor M; Ferrucci, Luigi

    2011-10-01

    Diabetes may impact gait mechanics before onset of frank neuropathies and other associated threats to mobility. This study aims to characterize gait pattern alterations of type 2 diabetic adults without peripheral neuropathy during walking at maximum speed (fast-walking) as well as at self-selected speed (usual-walking). One-hundred and eighty-six participants aged 60-87 from the Baltimore Longitudinal Study of Aging (BLSA) able to walk unassisted and without peripheral neuropathy were classified as non-diabetic (N=160) or having type 2 diabetes (N=26). Gait parameters from the fast-walking and usual-walking tests were compared between participants with and without type 2 diabetes. Participants with diabetes had a shorter stride length for fast-walking (p=0.033) and a longer percentage of the gait cycle with the knee in 1st flexion for both fast- and usual-walking (p=0.033, and 0.040, respectively) than non-diabetic participants. Participants with diabetes exhibited a smaller hip range of motion in the sagittal plane during usual-walking compared to non-diabetics (p=0.049). During fast-walking, participants with diabetes used lower ankle generative mechanical work expenditure (MWE) and higher knee absorptive MWE compared to non-diabetic persons (p=0.021, and 0.018, respectively). These findings suggest that individuals with type 2 diabetes without overt peripheral neuropathy exhibit altered and less efficient gait patterns than non-diabetic persons. These alterations are more apparent during walking at a maximum speed indicating that maximum gait testing may be useful for identifying early threats to mobility limitations in older adults with type 2 diabetes.

  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. 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

  7. The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum.

    PubMed

    Howard, Heidi C; Mount, David B; Rochefort, Daniel; Byun, Nellie; Dupré, Nicolas; Lu, Jianming; Fan, Xuemo; Song, Luyan; Rivière, Jean-Baptiste; Prévost, Claude; Horst, Jürgen; Simonati, Alessandro; Lemcke, Beate; Welch, Rick; England, Roger; Zhan, Frank Q; Mercado, Adriana; Siesser, William B; George, Alfred L; McDonald, Michael P; Bouchard, Jean-Pierre; Mathieu, Jean; Delpire, Eric; Rouleau, Guy A

    2002-11-01

    Peripheral neuropathy associated with agenesis of the corpus callosum (ACCPN) is a severe sensorimotor neuropathy associated with mental retardation, dysmorphic features and complete or partial agenesis of the corpus callosum. ACCPN is transmitted in an autosomal recessive fashion and is found at a high frequency in the province of Quebec, Canada. ACCPN has been previously mapped to chromosome 15q. The gene SLC12A6 (solute carrier family 12, member 6), which encodes the K+-Cl- transporter KCC3 and maps within the ACCPN candidate region, was screened for mutations in individuals with ACCPN. Four distinct protein-truncating mutations were found: two in the French Canadian population and two in non-French Canadian families. The functional consequence of the predominant French Canadian mutation (2436delG, Thr813fsX813) was examined by heterologous expression of wildtype and mutant KCC3 in Xenopus laevis oocytes; the truncated mutant is appropriately glycosylated and expressed at the cellular membrane, where it is non-functional. Mice generated with a targeted deletion of Slc12a6 have a locomotor deficit, peripheral neuropathy and a sensorimotor gating deficit, similar to the human disease. Our findings identify mutations in SLC12A6 as the genetic lesion underlying ACCPN and suggest a critical role for SLC12A6 in the development and maintenance of the nervous system.

  8. 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

  9. Weight-Bearing Versus Nonweight-Bearing Exercise for Persons With Diabetes and Peripheral Neuropathy: A Randomized Controlled Trial

    PubMed Central

    Mueller, Michael J.; Tuttle, Lori J.; LeMaster, Joseph W.; Strube, Michael J; McGill, Janet B.; Hastings, Mary K.; Sinacore, David R.

    2013-01-01

    Objective To determine the effects of weight-bearing (WB) versus nonweight-bearing (NWB) exercise for persons with diabetes mellitus (DM) and peripheral neuropathy (PN). Design Randomized controlled trial with evaluations at baseline and after intervention. Setting University-based physical therapy research clinic. Participants Participants with DM and PN (N=29) (mean age ± SD, 64.5±12.5y; mean body mass index [kg/m2] ± SD, 35.5±7.3) were randomly assigned to WB (n=15) and NWB (n=14) exercise groups. All participants (100%) completed the intervention and follow-up evaluations. Interventions Group-specific progressive balance, flexibility, strengthening, and aerobic exercise conducted sitting or lying (NWB) or standing and walking (WB) occurred 3 times a week for 12 weeks. Main Outcome Measures Measures included the 6-minute walk distance (6MWD) and daily step counts. Secondary outcome measures represented domains across the International Classification of Functioning, Disability and Health. Results The WB group showed greater gains than the NWB group over time on the 6MWD and average daily step count (P<.05). The mean and 95% confidence intervals (CIs) between-group difference over time was 29m (95% CI, 6–51) for the 6MWD and 1178 (95% CI, 150–2205) steps for the average daily step count. The NWB group showed greater improvements than the WB group over time in hemoglobin A1c values (P<.05). Conclusions The results of this study indicate the ability of this population with chronic disease to increase 6MWD and daily step count with a WB exercise program compared with an NWB exercise program. PMID:23276801

  10. 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

  11. 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.

  12. 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

  13. Electrical Stimulation as an Adjunctive Treatment of Painful and Sensory Diabetic Neuropathy

    PubMed Central

    Thakral, Gaurav; Kim, Paul J.; LaFontaine, Javier; Menzies, Robert; Najafi, Bijan; Lavery, Lawrence A.

    2013-01-01

    Background The objective of this review is to evaluate the use of electrical stimulation to treat diabetic neuropathy. Application of electrical stimulation may provide a novel treatment option for large and small fiber neuropathy in persons with diabetes. Large and small nerve neuropathy alters pain, proprioception, touch perception, and motor function, which cause burning foot pain and serve as protective mechanisms from ulcerations. Methods A content search for clinical trials involving electrical stimulation, neuropathy, and diabetes was conducted through PubMed. Randomized clinical trials and prospective studies with outcome measures affecting the lower extremity function were selected for review. Results We identified eight studies in which electrical stimulation was used to treat diabetic neuropathy. Six studies evaluated small fiber neuropathy. Two studies evaluated patients with both small and large fiber neuropathy and reported significant improvement in vibration and monofilament testing and reduction in symptoms in the electrical stimulation treatment group. Six of the eight painful neuropathy studies identified significant improvement in symptoms. There were no studies that evaluated electrical stimulation to treated diabetic motor neuropathy, fall prevention or postural instability. Conclusions Electrical stimulation may be an effective alternative and adjunctive therapy to current interventions for diabetic peripheral neuropathy. PMID:24124947

  14. Clinical description of toxic neuropathies.

    PubMed

    Little, Ann A; Albers, James W

    2015-01-01

    Toxic neuropathy, although rare, is an important consideration in the setting of a known or suspected toxic exposure in the workplace or other environment. This chapter discusses the clinical and electrodiagnostic evaluation of peripheral neuropathies, highlighting findings that direct further workup and may point to specific toxins as etiology. The difficulty of establishing causality of a toxin in relation to peripheral neuropathy is discussed; guidelines for establishing causality are presented. Examples of common industrial toxins are listed, including their typical industrial uses and their mechanisms of action in producing neuropathy. Characteristic clinical presentations of specific toxic neuropathies are highlighted with selected case studies. PMID:26563794

  15. Early onset (childhood) monogenic neuropathies.

    PubMed

    Landrieu, Pierre; Baets, Jonathan

    2013-01-01

    Hereditary neuropathies (HN) with onset in childhood are categorized according to clinical presentation, pathogenic mechanism based on electrophysiology, genetic transmission and, in selected cases, pathological findings. Especially relevant to pediatrics are the items "secondary" versus "primary" neuropathy, "syndromic versus nonsyndromic," and "period of life." Different combinations of these parameters frequently point toward specific monogenic disorders. Ruling out a neuropathy secondary to a generalized metabolic disorder remains the first concern in pediatrics. As a rule, metabolic diseases include additional, orienting symptoms or signs, and their biochemical diagnosis is based on logical algorithms. Primary, motor sensory are the most frequent HN and are dominated by demyelinating autosomal dominant (AD) forms (CMT1). Other forms include demyelinating autosomal recessive (AR) forms, axonal AD/AR forms, and forms with "intermediate" electrophysiological phenotype. Peripheral motor neuron disorders are dominated by AR SMN-linked spinal muscular atrophies. (Distal) hereditary motor neuropathies represent <10% of HN but exhibit large clinical and genetic heterogeneity. Sensory/dysautonomic HN involves five classic subtypes, each one related to specific genes. However, genetic heterogeneity is larger than initially suspected. Syndromic HN distinguish "purely neurological syndromes", which are multisystemic, such as spinocerebellar atrophies +, spastic paraplegias +, etc. Peripheral neuropathy is possibly the presenting feature, including in childhood. Autosomal recessive forms, on average, start more frequently in childhood. "Multiorgan syndromes", on the other hand, are more specific to Pediatrics. AR forms, which are clearly degenerative, prompt the investigation of a large set of pleiotropic genes. Other syndromes expressed in the perinatal period are mainly developmental disorders, and can sometimes be related to specific transcription factors. Systematic

  16. 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

  17. 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.

  18. 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.

  19. 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 ...

  20. 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

  1. 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

  2. A meta-analysis of trials on aldose reductase inhibitors in diabetic peripheral neuropathy. The Italian Study Group. The St. Vincent Declaration.

    PubMed

    Nicolucci, A; Carinci, F; Cavaliere, D; Scorpiglione, N; Belfiglio, M; Labbrozzi, D; Mari, E; Benedetti, M M; Tognoni, G; Liberati, A

    1996-12-01

    Peripheral neuropathy is one of the most common and disabling long-term sequelae of diabetes mellitus. Aldose reductase inhibitors (ARIs) have been proposed and are increasingly used in many countries for the prevention and treatment of diabetic neuropathy. The aim of this study was to review existing evidence on the effectiveness of ARIs in the treatment of peripheral diabetic neuropathy, with particular reference to the type and clinical relevance of the end point used and to the consistency of results across studies. Thirteen randomized clinical trials (RTCs) comparing ARIs with placebo, published between 1981 and 1993 were included in the meta-analysis. Nerve conduction velocity (NCV) was the only end point reported in all trials. Treatment effect was thus evaluated in terms of NCV mean difference in four different nerves: median motor, median sensory, peroneal motor, and sural sensory. A statistically significant reduction in decline of median motor NCV was present in the treated group as compared to the control group (mean 0.91 ms-1; 95% CI 0.41-1.42 ms-1). For peroneal motor, median sensory, and sural sensory nerves results did not show any clear benefit for patients treated with ARIs. When the analysis was limited to trials with at least 1-year treatment duration, a significant effect was present for peroneal motor NCV (mean 1.24 ms-1; 95% CI 0.32-2.15 ms-1) and a benefit of borderline statistical significance was also present for median motor NCV (mean 0.69 ms-1; 95% CI-0.07-1.45 ms-1). A heterogeneous picture emerged when looking at the results of different studies and serious inconsistencies were also present in the direction of treatment effects among nerves in the same studies. Although the results of 1-year treatment on motor NCV seem encouraging, the uncertainty about the reliability of the end-point employed and the short treatment duration do not allow any clear conclusion about the efficacy of ARIs in the treatment of peripheral diabetic

  3. Enriching the diet with menhaden oil improves peripheral neuropathy in streptozotocin-induced type 1 diabetic rats.

    PubMed

    Coppey, Lawrence J; Davidson, Eric P; Obrosov, Alexander; Yorek, Mark A

    2015-02-01

    The purpose of this study was to determine the effect of supplementing the diet of type 1 diabetic rats with menhaden oil on diabetic neuropathy. Menhaden oil is a natural source for n-3 fatty acids, which have been shown to have beneficial effects in cardiovascular disease and other morbidities. Streptozotocin-induced diabetic rats were used to examine the influence of supplementing their diet with 25% menhaden oil on diabetic neuropathy. Both prevention and intervention protocols were used. Endpoints included motor and sensory nerve conduction velocity, thermal and mechanical sensitivity, and innervation and sensitivity of the cornea and hindpaw. Diabetic neuropathy as evaluated by the stated endpoints was found to be progressive. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels. Diabetic rats at 16-wk duration were thermal hypoalgesic and had reduced motor and sensory nerve conduction velocities, and innervation and sensitivity of the cornea and skin were impaired. These endpoints were significantly improved with menhaden oil treatment following the prevention or intervention protocol. We found that supplementing the diet of type 1 diabetic rats with menhaden oil improved a variety of endpoints associated with diabetic neuropathy. These results suggest that enriching the diet with n-3 fatty acids may be a good treatment strategy for diabetic neuropathy.

  4. Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith-Magenis syndrome with evident peripheral neuropathy.

    PubMed

    Yuan, Bo; Neira, Juanita; Gu, Shen; Harel, Tamar; Liu, Pengfei; Briceño, Ignacio; Elsea, Sarah H; Gómez, Alberto; Potocki, Lorraine; Lupski, James R

    2016-10-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) and Smith-Magenis syndrome (SMS) are genomic disorders associated with deletion copy number variants involving chromosome 17p12 and 17p11.2, respectively. Nonallelic homologous recombination (NAHR)-mediated recurrent deletions are responsible for the majority of HNPP and SMS cases; the rearrangement products encompass the key dosage-sensitive genes PMP22 and RAI1, respectively, and result in haploinsufficiency for these genes. Less frequently, nonrecurrent genomic rearrangements occur at this locus. Contiguous gene duplications encompassing both PMP22 and RAI1, i.e., PMP22-RAI1 duplications, have been investigated, and replication-based mechanisms rather than NAHR have been proposed for these rearrangements. In the current study, we report molecular and clinical characterizations of six subjects with the reciprocal phenomenon of deletions spanning both genes, i.e., PMP22-RAI1 deletions. Molecular studies utilizing high-resolution array comparative genomic hybridization and breakpoint junction sequencing identified mutational signatures that were suggestive of replication-based mechanisms. Systematic clinical studies revealed features consistent with SMS, including features of intellectual disability, speech and gross motor delays, behavioral problems and ocular abnormalities. Five out of six subjects presented clinical signs and/or objective electrophysiologic studies of peripheral neuropathy. Clinical profiling may improve the clinical management of this unique group of subjects, as the peripheral neuropathy can be more severe or of earlier onset as compared to SMS patients having the common recurrent deletion. Moreover, the current study, in combination with the previous report of PMP22-RAI1 duplications, contributes to the understanding of rare complex phenotypes involving multiple dosage-sensitive genes from a genetic mechanistic standpoint.

  5. Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith-Magenis syndrome with evident peripheral neuropathy.

    PubMed

    Yuan, Bo; Neira, Juanita; Gu, Shen; Harel, Tamar; Liu, Pengfei; Briceño, Ignacio; Elsea, Sarah H; Gómez, Alberto; Potocki, Lorraine; Lupski, James R

    2016-10-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) and Smith-Magenis syndrome (SMS) are genomic disorders associated with deletion copy number variants involving chromosome 17p12 and 17p11.2, respectively. Nonallelic homologous recombination (NAHR)-mediated recurrent deletions are responsible for the majority of HNPP and SMS cases; the rearrangement products encompass the key dosage-sensitive genes PMP22 and RAI1, respectively, and result in haploinsufficiency for these genes. Less frequently, nonrecurrent genomic rearrangements occur at this locus. Contiguous gene duplications encompassing both PMP22 and RAI1, i.e., PMP22-RAI1 duplications, have been investigated, and replication-based mechanisms rather than NAHR have been proposed for these rearrangements. In the current study, we report molecular and clinical characterizations of six subjects with the reciprocal phenomenon of deletions spanning both genes, i.e., PMP22-RAI1 deletions. Molecular studies utilizing high-resolution array comparative genomic hybridization and breakpoint junction sequencing identified mutational signatures that were suggestive of replication-based mechanisms. Systematic clinical studies revealed features consistent with SMS, including features of intellectual disability, speech and gross motor delays, behavioral problems and ocular abnormalities. Five out of six subjects presented clinical signs and/or objective electrophysiologic studies of peripheral neuropathy. Clinical profiling may improve the clinical management of this unique group of subjects, as the peripheral neuropathy can be more severe or of earlier onset as compared to SMS patients having the common recurrent deletion. Moreover, the current study, in combination with the previous report of PMP22-RAI1 duplications, contributes to the understanding of rare complex phenotypes involving multiple dosage-sensitive genes from a genetic mechanistic standpoint. PMID:27386852

  6. Effect of diet-induced obesity or type 1 or type 2 diabetes on corneal nerves and peripheral neuropathy in C57Bl/6J mice.

    PubMed

    Yorek, Matthew S; Obrosov, Alexander; Shevalye, Hanna; Holmes, Amey; Harper, Matthew M; Kardon, Randy H; Yorek, Mark A

    2015-03-01

    We determined the impact diet-induced obesity (DIO) and types 1 and 2 diabetes have on peripheral neuropathy with emphasis on corneal nerve structural changes in C57Bl/6J mice. Endpoints examined included nerve conduction velocity, response to thermal and mechanical stimuli and innervation of the skin and cornea. DIO mice and to a greater extent type 2 diabetic mice were insulin resistant. DIO and both types 1 and 2 diabetic mice developed motor and sensory nerve conduction deficits. In the cornea of DIO and type 2 diabetic mice there was a decrease in sub-epithelial corneal nerves, innervation of the corneal epithelium, and corneal sensitivity. Type 1 diabetic mice did not present with any significant changes in corneal nerve structure until after 20 weeks of hyperglycemia. DIO and type 2 diabetic mice developed corneal structural damage more rapidly than type 1 diabetic mice although hemoglobin A1 C values were significantly higher in type 1 diabetic mice. This suggests that DIO with or without hyperglycemia contributes to development and progression of peripheral neuropathy and nerve structural damage in the cornea.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. Mitochondrial protein alterations in a familial peripheral neuropathy caused by the V144D amino acid mutation in the sphingolipid protein, SPTLC1.

    PubMed

    Stimpson, Scott E; Coorssen, Jens R; Myers, Simon J

    2015-01-01

    Axonal degeneration is the final common path in many neurological disorders. Subsets of neuropathies involving the sensory neuron are known as hereditary sensory neuropathies (HSNs). Hereditary sensory neuropathy type I (HSN-I) is the most common subtype of HSN with autosomal dominant inheritance. It is characterized by the progressive degeneration of the dorsal root ganglion (DRG) with clinical symptom onset between the second or third decade of life. Heterozygous mutations in the serine palmitoyltransferase (SPT) long chain subunit 1 (SPTLC1) gene were identified as the pathogenic cause of HSN-I. Ultrastructural analysis of mitochondria from HSN-I patient cells has displayed unique morphological abnormalities that are clustered to the perinucleus where they are wrapped by the endoplasmic reticulum (ER). This investigation defines a small subset of proteins with major alterations in abundance in mitochondria harvested from HSN-I mutant SPTLC1 cells. Using mitochondrial protein isolates from control and patient lymphoblasts, and a combination of 2D gel electrophoresis, immunoblotting and mass spectrometry, we have shown the increased abundance of ubiquinol-cytochrome c reductase core protein 1, an electron transport chain protein, as well as the immunoglobulin, Ig kappa chain C. The regulation of these proteins may provide a new route to understanding the cellular and molecular mechanisms underlying HSN-I. PMID:25584079

  13. Heme oxygenase-1, a novel target for the treatment of diabetic complications: focus on diabetic peripheral neuropathy.

    PubMed

    Negi, Geeta; Nakkina, Vanaja; Kamble, Pallavi; Sharma, Shyam S

    2015-12-01

    Diabetic neuropathy is a complex disorder induced by long standing diabetes. Many signaling pathways and transcription factors have been proposed to be involved in the development and progression of related processes. Years of research points to critical role of oxidative stress, neuroinflammation and apoptosis in the pathogenesis of neuropathy in diabetes. Heme oxygenase-1 (HO-1) is heat-shock protein induced under conditions of different kinds of stress and has been implicated in cellular defense against oxidative stress. HO-1 degrades heme to biliverdin, carbon monoxide (CO) and free iron. Biliverdin and CO are gaining particular interest because these two have been found to mediate most of anti-inflammatory, antioxidant and anti-apoptotic effects of HO-1. Although extensively studied in different kinds of cancers and cardiovascular conditions, role of HO-1 in diabetic neuropathy is still under investigation. In this paper, we review the unique therapeutic potential of HO-1 and its role in mitigating various pathological processes that lead to diabetic neuropathy. This review also highlights the therapeutic approaches such as pharmacological and natural inducers of HO-1, gene delivery of HO-1 or its reaction products that in future, could lead to progression of HO-1 activators through the preclinical stages of drug development to clinical trials.

  14. Acetylator phenotype in diabetic neuropathy.

    PubMed Central

    McLaren, E H; Burden, A C; Moorhead, P J

    1977-01-01

    The proportions of slow and fast acetylators in a group of diabetics with symptomatic peripheral neuropathy were compared with those in a group of diabetics who had had the disease for at least 10 years without developing neuropathy. There was a significantly higher proportion of fast acetylators in the group of diabetics without neuropathy than in those with neuropathy or in the normal population. Hence genetic factors separate from the diabetic diathesis may determine the development of neuropathy in any particular diabetic. PMID:871863

  15. [Painful neuropathies and small fiber involvement].

    PubMed

    Lefaucheur, J-P

    2014-12-01

    It is customary to consider that a purely sensory and painful neuropathy accompanied by normal electroneuromyographic examination may be or must be a small fiber neuropathy. This leads to perform specific tests, such as measuring the intra-epidermal nerve fiber density on skin biopsy or neurophysiological tests, such as evoked potentials to noxious stimuli (laser) or quantification of thermal sensory thresholds. However, these tests are only sensitive to the loss of small fibers (A-delta and C), which does not reflect the mechanisms responsible for peripheral neuropathic pain. Selective loss of small sensory fibers inherently generates a sensory deficit that does not necessarily present a painful character. Also, assigning the cause of a painful neuropathy to a small fiber neuropathy has no pathophysiological sense, although there are indirect links between these two conditions. In fact, it is not possible to explain univocally peripheral neuropathic pain, which reflects complex and diverse mechanisms, involving different types of nerve fibers. In this context, the clinical and laboratory approach must be improved to better understand the underlying mechanisms. It is imperative to interpret the data provided by laboratory tests and to correlate these data to the clinical signs and symptoms presented by the patients. Thus, one must go beyond many a priori and misinterpretations that unfortunately exist in this area at present and are not based on any solid pathophysiological basis.

  16. 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.

  17. Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes

    PubMed Central

    DREL, VIKTOR R.; PACHER, PAL; VARENIUK, IGOR; PAVLOV, IVAN A.; ILNYTSKA, OLGA; LYZOGUBOV, VALERIY V.; BELL, SETH R.; GROVES, JOHN T.; OBROSOVA, IRINA G.

    2008-01-01

    Whereas the important role of free radicals in diabetes-associated complications is well established, the contributions of the highly reactive oxidant peroxynitrite have not been properly explored. The present study used a pharmacological approach to evaluate the role of peroxynitrite in peripheral diabetic neuropathy. Control and STZ-diabetic mice were maintained with or without treatment with the potent peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate (FeTMPS), at doses of 5 or 10 mg/kg/day in the drinking water for 3 weeks after an initial 3 weeks without treatment. Mice with a 6-week duration of diabetes developed clearly manifest motor (MNCV) and sensory nerve conduction velocity (SNCV) deficits, thermal hypoalgesia (paw withdrawal, tail-flick, and hot plate tests), mechanical hypoalgesia (tail pressure Randall-Sellito test), tactile allodynia (flexible von Frey filament test), and ~44% loss of intraepidermal nerve fibers. They also had increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in sciatic nerve, grey matter of the spinal cord, and dorsal root ganglion neurons. FeTMPS treatment alleviated or essentially corrected (at a dose of 10 mg/kg/day) MNCV and SNCV deficits, and was associated with less severe small sensory nerve fiber dysfunction and degeneration. Nitrotyrosine and poly(ADP-ribose) immunofluorescence in sciatic nerve, spinal cord, and dorsal root ganglion neurons in peroxynitrite decomposition catalyst-treated diabetic mice was markedly reduced. In conclusion, peroxynitrite contributes to large motor, large sensory, and small sensory fiber neuropathy in streptozotocin-diabetic mice. The findings provide rationale for development of potent peroxynitrite decomposition catalysts for the treatment of diabetic neuropathy. PMID:17982684

  18. Micronized Palmitoylethanolamide Reduces the Symptoms of Neuropathic Pain in Diabetic Patients

    PubMed Central

    Schifilliti, Chiara; Cucinotta, Lelio; Fedele, Viviana; Ingegnosi, Carmela; Luca, Salvatore; Leotta, Carmelo

    2014-01-01

    The present study evaluated the effectiveness of micronized palmitoylethanolamide (PEA-m) treatment in reducing the painful symptoms experienced by diabetic patients with peripheral neuropathy. PEA-m, a fatty acid amide of the N-acylethanolamine family, was administered (300 mg twice daily) to 30 diabetic patients suffering from painful diabetic neuropathy. Before treatment start, after 30 and 60 days the following parameters were assessed: painful symptoms of diabetic peripheral neuropathy using the Michigan Neuropathy Screening instrument; intensity of symptoms characteristic of diabetic neuropathic pain by the Total Symptom Score; and intensity of different subcategories of neuropathic pain by the Neuropathic Pain Symptoms Inventory. Hematological and blood chemistry tests to evaluate metabolic control and safety were also performed. Statistical analysis (ANOVA) indicated a highly significant reduction in pain severity (P < 0.0001) and related symptoms (P < 0.0001) evaluated by Michigan Neuropathy Screening instrument, Total Symptom Score, and Neuropathic Pain Symptoms Inventory. Hematological and urine analyses did not reveal any alterations associated with PEA-m treatment, and no serious adverse events were reported. These results suggest that PEA-m could be considered as a promising and well-tolerated new treatment for symptomatology experienced by diabetic patients suffering from peripheral neuropathy. PMID:24804094

  19. Micronized palmitoylethanolamide reduces the symptoms of neuropathic pain in diabetic patients.

    PubMed

    Schifilliti, Chiara; Cucinotta, Lelio; Fedele, Viviana; Ingegnosi, Carmela; Luca, Salvatore; Leotta, Carmelo

    2014-01-01

    The present study evaluated the effectiveness of micronized palmitoylethanolamide (PEA-m) treatment in reducing the painful symptoms experienced by diabetic patients with peripheral neuropathy. PEA-m, a fatty acid amide of the N-acylethanolamine family, was administered (300 mg twice daily) to 30 diabetic patients suffering from painful diabetic neuropathy. Before treatment start, after 30 and 60 days the following parameters were assessed: painful symptoms of diabetic peripheral neuropathy using the Michigan Neuropathy Screening instrument; intensity of symptoms characteristic of diabetic neuropathic pain by the Total Symptom Score; and intensity of different subcategories of neuropathic pain by the Neuropathic Pain Symptoms Inventory. Hematological and blood chemistry tests to evaluate metabolic control and safety were also performed. Statistical analysis (ANOVA) indicated a highly significant reduction in pain severity (P < 0.0001) and related symptoms (P < 0.0001) evaluated by Michigan Neuropathy Screening instrument, Total Symptom Score, and Neuropathic Pain Symptoms Inventory. Hematological and urine analyses did not reveal any alterations associated with PEA-m treatment, and no serious adverse events were reported. These results suggest that PEA-m could be considered as a promising and well-tolerated new treatment for symptomatology experienced by diabetic patients suffering from peripheral neuropathy. PMID:24804094

  20. 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

  1. Screening for mutations in the peripheral myelin genes PMP22, MPZ and Cx32 (GJB1) in Russian Charcot-Marie-Tooth neuropathy patients.

    PubMed

    Mersiyanova, I V; Ismailov, S M; Polyakov, A V; Dadali, E L; Fedotov, V P; Nelis, E; Löfgren, A; Timmerman, V; van Broeckhoven, C; Evgrafov, O V

    2000-01-01

    Charcot-Marie-Tooth disease (CMT) and related inherited peripheral neuropathies, including Dejerine-Sottas syndrome, congenital hypomyelination, and hereditary neuropathy with liability to pressure palsies (HNPP), are caused by mutations in three myelin genes: PMP22, MPZ and Cx32 (GJB1). The most common mutations are the 1.5 Mb CMT1A tandem duplication on chromosome 17p11.2-p12 in CMT1 patients and the reciprocal 1.5 Mb deletion in HNPP patients. We performed a mutation screening in 174 unrelated CMT patients and three HNPP families of Russian origin. The unrelated CMT patients included 108 clinically and electrophysiologically diagnosed CMT1 cases, 32 CMT2 cases, and 34 cases with unspecified CMT. Fifty-nine CMT1A duplications were found, of which 58 belonged to the CMT1 patient group. We found twelve distinct mutations in Cx32, six mutations in MPZ, and two mutations in PMP22. Of these respectively, eight, five, and two lead to a CMT1 phenotype. Eight mutations (Cx32: Ile20Asn/Gly21Ser, Met34Lys, Leu90Val, and Phe193Leu; MPZ: Asp134Gly, Lys138Asn, and Thr139Asn; PMP22: ValSer25-26del) were not reported previously. Phenotype-genotype correlations were based on nerve conduction velocity studies and mutation type. PMID:10737979

  2. 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 ...

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy.

    PubMed

    Isaacs, Adrian M; Jeans, Alexander; Oliver, Peter L; Vizor, Lucie; Brown, Steve D M; Hunter, A Jackie; Davies, Kay E

    2002-09-01

    We have identified and characterized a new peripheral myelin protein 22 (Pmp22) mouse mutant. The mutation results in a serine to threonine amino acid substitution at residue 72, which is a hot spot for mutation in human PMP22, leading to the peripheral neuropathy Dejerine-Sottas syndrome. We have previously described two other Pmp22 mutants, providing an allelic series for gene function analysis. Pmp22 mutations generally lead to abnormal intracellular trafficking of Pmp22, and we show that each mutant protein in the allelic series has a unique pattern of intracellular localization in transfected cell lines. The mutant protein from the less severely affected mutants occurs in large aggregates, while the mutant protein from the most severely affected mutant occurs in a diffuse perinuclear pattern that largely colocalizes with wild-type protein. This suggests that large Pmp22 aggregates may be protective in this form of peripheral neuropathy. PMID:12359155

  8. Peripheral eosinophilia and respiratory symptoms in rubber injection press operators: a case-control study.

    PubMed

    Thomas, R J; Bascom, R; Yang, W N; Fisher, J F; Baser, M E; Greenhut, J; Baker, J H

    1986-01-01

    To evaluate a suspected association between an outbreak of acute respiratory illness and eosinophilia and employment as a rubber worker, we performed a retrospective review of medical records of rubber workers employed from September 1983 to July 1984 in a plant housing a thermoinjection process. Twenty-five workers met the case definition of a respiratory illness requiring a physician visit. The predominant respiratory illness was acute in onset with cough, chest tightness, and dyspnea. Peripheral eosinophilia, up to 40% of white blood cells in a peripheral smear, was seen in 10 of 18 (56%) cases. Twenty-one of 25 white males with respiratory symptoms were employed in the thermoinjection process (odds ratio = 22, p less than .001). Smoking and employment in this process contributed independently to an increased risk of being a case as determined by a logistic regression analysis. Return to the plant building caused recurrence of symptoms in most cases, and these workers have been transferred or left the company. We conclude that a strong previously unrecognized association exists between employment in this neoprene rubber thermoinjection process and the development of an acute respiratory illness.

  9. A case report of gastric cancer with brain metastasis: Rare peripheral nervous system symptoms

    PubMed Central

    YANG, GE-LIANG; LUO, TIAN-HANG; ZHANG, HUI-QING; LING, CHANG-QUAN; LI, BAI

    2016-01-01

    Gastric cancer with brain metastasis is rare. The present study reports a case of gastric cancer with isolated brain metastasis 1 year after gastrectomy. To the best of our knowledge, there have been no prior reports of solitary brain metastasis from gastric cancer with peripheral nervous system symptoms. A distal gastrectomy was performed on a 60-year-old male patient with gastric cancer in November 2012. Postoperative pathological analysis revealed a moderately differentiated adenocarcinoma with tumor invasion into the serosa and metastasis to one dissected lymph node. No abnormalities were found at follow-up examination. However, a tumor representing metastasis to the brain was recognized by a cranial enhanced magnetic resonance imaging examination 1 year after gastrectomy, which was performed when the patient exhibited numbness and thigmesthesia. The patient was administered 30 Gy of stereotactic radiotherapy, delivered in 5 fractions. The patient succumbed to disease 10 months subsequent to undergoing radiotherapy. This case report suggests that gastric cancer may re-present as brain metastasis with peripheral nervous system symptoms. PMID:27073571

  10. 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

  11. Effects of eribulin, vincristine, paclitaxel and ixabepilone on fast axonal transport and kinesin-1 driven microtubule gliding: Implications for chemotherapy-induced peripheral neuropathy

    PubMed Central

    LaPointe, Nichole E.; Morfini, Gerardo; Brady, Scott T.; Feinstein, Stuart C.; Wilson, Leslie; Jordan, Mary Ann

    2014-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a serious, painful and dose-limiting side effect of cancer drugs that target microtubules. The mechanisms underlying the neuronal damage are unknown, but may include disruption of fast axonal transport, an essential microtubule-based process that moves cellular components over long distances between neuronal cell bodies and nerve terminals. This idea is supported by the “dying back” pattern of degeneration observed in CIPN, and by the selective vulnerability of sensory neurons bearing the longest axonal projections. In this study, we test the hypothesis that microtubule-targeting drugs disrupt fast axonal transport using vesicle motility assays in isolated squid axoplasm and a cell-free microtubule gliding assay with defined components. We compare four clinically-used drugs, eribulin, vincristine, paclitaxel and ixabepilone. Of these, eribulin is associated with a relatively low incidence of severe neuropathy, while vincristine has a relatively high incidence. In vesicle motility assays, we found that all four drugs inhibited anterograde (conventional kinesin-dependent) fast axonal transport, with the potency being vincristine = ixabepilone > paclitaxel = eribulin. Interestingly, eribulin and paclitaxel did not inhibit retrograde (cytoplasmic dynein-dependent) fast axonal transport, in contrast to vincristine and ixabepilone. Similarly, vincristine and ixabepilone both exerted significant inhibitory effects in an in vitro microtubule gliding assay consisting of recombinant kinesin (kinesin-1) and microtubules composed of purified bovine brain tubulin, whereas paclitaxel and eribulin had negligible effects. Our results suggest that (i) inhibition of microtubule-based fast axonal transport may be a significant contributor to neurotoxicity induced by microtubule-targeting drugs, and (ii) that individual microtubule-targeting drugs affect fast axonal transport through different mechanisms. PMID:23711742

  12. The expanding spectrum of PRPS1-associated phenotypes: three novel mutations segregating with X-linked hearing loss and mild peripheral neuropathy

    PubMed Central

    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

    2015-01-01

    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

  13. 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

  14. 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

  15. Toxic neuropathies.

    PubMed

    Misra, Usha Kant; Kalita, Jayantee

    2009-01-01

    Toxic neuropathies generally result in length dependent axonal neuropathy with the exception of diphtheria and a few toxic neuropathies. In spite of occurrence of diphtheria in India there is paucity of published reports on diphtheritic neuropathy. Arsenic neuropathy commonly occurs in Bengal and Bangladesh because of ground water contamination whereas in Punjab it is due to contamination of opium. Lead neuropathy is rare and has been reported in battery workers and silver refining workers. It produces motor neuropathy resulting in foot drop and wrist drop. Organophosphates are used as pesticides, industrial chemicals and food adulterant. Certain organophosphates such as triorthocresyl phosphate used for or oil adulteration inhibit neurotoxic esterase and result in a delayed type of axonal neuropathy. Alcohol related neuropathy is a controversial issue whether it is due to alcohol related toxicity or due to nutritional deficiencies. Indian studies have revealed that neuropathy occurs both in alcoholic and nonalcoholic cirrhosis. Hexane neuropathy is reported in screen printers and these cases highlight the need for better preventive and occupational measures. Iatrogenic toxic neuropathies have been reported with cisplatin and vincristine. Because of geographical, occupational and health related conditions toxic neuropathies are likely to be more common than reported and greater awareness is needed.

  16. 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

  17. 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 ...

  18. 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 ...

  19. Poor efficacy of the phosphorylated high-molecular-weight neurofilament heavy subunit serum level, a biomarker of axonal damage, as a marker of chemotherapy-induced peripheral neuropathy

    PubMed Central

    SUMITANI, MASAHIKO; OGATA, TORU; NATORI, AKINA; HOZUMI, JUN; SHIMOJO, NOBUTAKE; KIDA, KUMIKO; YAMAUCHI, HIDEKO; YAMAUCHI, TERUO

    2016-01-01

    The phosphorylated form of the high-molecular-weight neurofilament heavy subunit (pNF-H) is a major structural protein in axons. The pNF-H level is elevated in the serum of certain patients with central nervous disorders, including chemotherapy-induced cognitive impairment. The present study was conducted to elucidate the potential role of pNF-H as a marker of chemotherapy-induced peripheral neuropathy (CIPN). A total of 71 patients with early breast cancer in various stages of treatment (following 1, 3 or 7 cycles of chemotherapy, or a previous history of breast cancer chemotherapy) were assessed with a self-administered PainDETECT questionnaire [pain location, pain intensity on an 11-point numeric rating scale (NRS), and various pain qualities] and a single serum pNF-H measurement. Patients were divided into two groups based on the presence or absence of bilateral symmetric pain in the distal portions of the extremities [CIPN(+) or CIPN(−)]. The χ2 and Mann-Whitney tests were used for statistical analyses. Among the participants, only 8 patients complained of CIPN. Their pain intensity was 3.5±1.9 (mean ± standard deviation) compared with 1.5±1.8 in the CIPN(−) group (P<0.01). The NRS of numbness in the CIPN(+) group was significantly higher (2.4±1.4) than that of the CIPN(−) group (1.0±1.0). Increased pNF-H levels were observed in 37.5% of the CIPN(+) patients and in 23.8% of CIPN(−) patients (P=0.40). In conclusion, CIPN is observed in the most distal portions of the peripheral nerves that are composed of dendrites but not axons. Although serum pNF-H is a biomarker of axonal damage, it is not useful as a marker of CIPN. PMID:27284419

  20. Mitochondrial DNA Subhaplogroups L0a2 and L2a Modify Susceptibility to Peripheral Neuropathy in Malawian Adults on Stavudine Containing Highly Active Antiretroviral Therapy

    PubMed Central

    Kampira, Elizabeth; Kumwenda, Johnstone; van Oosterhout, Joep J.

    2013-01-01

    Background: Peripheral neuropathy (PN) is one of the main toxicities associated with stavudine. Genetic variants in mitochondrial DNA (mtDNA) haplogroups have been associated with increased risk of developing PN in European non-Hispanic and black patients on stavudine containing antiretroviral therapy (ART). We investigated mtDNA haplogroups and their role in susceptibility to stavudine-induced peripheral in Malawian patients on ART. Method: Two hundred and fifteen adults on stavudine containing regimens were recruited from the ART clinic at Queen Elizabeth Central Hospital, Blantyre, into a cross-sectional study to investigate the effects of genetic variants in mtDNA of individuals in relation to response to treatment. Patients were categorized according to whether or not they had developed PN after a minimum of 6 months on stavudine containing ART. Whole mtDNA coding regions of each patient were sequenced, and CD4 count, viral load, and creatinine were determined. The mtDNA variation was correlated with clinical characteristics. Results: Fifty-three (25%) of the participants developed PN after starting stavudine containing ART. Mitochondrial DNA subhaplogroup L0a2 was independently associated with increased risk of PN in a multivariate model (odds ratio, 2.23; 95% confidence interval, 1.14 to 4.39; P = 0.019), and subhaplogroup L2a was independently associated with reduced risk of PN (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.94; P = 0.036). Conclusions: Genetic variation in mtDNA confers differential risk of developing PN in patients on stavudine containing ART among Malawians. PMID:23614993

  1. Combined Therapy of Diabetic Peripheral Neuropathy with Breviscapine and Mecobalamin: A Systematic Review and a Meta-Analysis of Chinese Studies

    PubMed Central

    Ou, Weilin; Shen, Huanyu; Zhou, Zhiheng; Wang, Jiaji

    2015-01-01

    Objective. A meta-analysis on combined therapy of diabetic peripheral neuropathy (DPN) with breviscapine and mecobalamin was performed to evaluate the efficacy of this therapy. Methods. Six English databases (Medline, Cochrane Library, PubMed, EMBASE, Web of Science, and CINAHL) and four Chinese databases (China National Knowledge Infrastructure, VIP Journals Database, CBM, and Wanfang database) were searched for studies on the clinical trials in which DPN was treated with breviscapine and mecobalamin, and RevMan 5.1 package was employed for analyzing pooled trials and publication bias. Results. A total of 17 articles including 1398 DPN patients were identified. Homogeneity was observed among different studies (P = 0.74). The efficacy of combined therapy with breviscapine and mecobalamin was significantly better than that in control group [P < 0.0001 (OR = 5.01, 95% CI: 3.70–6.78)]. Conclusion. Available findings suggest that the therapeutic efficacy of breviscapine combining mecobalamin is superior to mecobalamin alone, and this strategy is required to be popularized in clinical practice. PMID:25866802

  2. 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

  3. Depleting endogenous neurotrophin-3 enhances myelin formation in the Trembler-J mouse, a model of a peripheral neuropathy.

    PubMed

    Liu, Ning; Varma, Sushama; Tsao, David; Shooter, Eric M; Tolwani, Ravi J

    2007-10-01

    The heterozygous Trembler-J (TrJ/+) mouse, containing a point mutation in the peripheral myelin protein 22 (Pmp22) gene, is characterized by severe hypomyelination and is a representative model of Charcot-Marie-Tooth 1A (CMT1A) disease/Dejerine-Sottas syndrome (DSS). Given that the neurotrophin-3 (NT3)-TrkC signaling pathway is inhibitory to myelination during development, we investigated the role of the NT3-TrkC pathway in myelination and manipulated this pathway to improve myelin formation in the CMT1A/DSS mouse model. Injection of NT3 to the TrJ/+ mice decreased the myelin protein P(0) level in the sciatic nerves. Suppressing the NT3-TrkC pathway with TrkC-Fc, an NT3 scavenger, enhanced myelination in vitro and in vivo in the TrJ/+ mouse. Furthermore, we found that full-length TrkC was expressed in adult TrJ/+ mouse sciatic nerves but was not detected in the wild-type adults, suggesting that the full-length TrkC is a potential target of treatment to enhance myelination in the TrJ/+ mouse. PMID:17628499

  4. 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

    2015-05-18

    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.

  5. The association between foot-care self efficacy beliefs and actual foot-care behaviour in people with peripheral neuropathy: a cross-sectional study

    PubMed Central

    Perrin, Byron M; Swerissen, Hal; Payne, Craig

    2009-01-01

    Background People with diabetes and peripheral neuropathy often do not implement the foot-care behavioural strategies that are suggested by many health professionals. The concept of self-efficacy has been shown to be an effective predictor of behaviour in many areas of health. This study investigated the relationships between foot-care self-efficacy beliefs, self-reported foot-care behaviour and history of diabetes-related foot pathology in people with diabetes and loss of protective sensation in their feet. Methods Ninety-six participants were included in this cross-sectional study undertaken in a regional city of Australia. All participants had diabetes and clinically diagnosed loss of protective sensation in their feet. The participants completed a self-report pen-paper questionnaire regarding foot-care self efficacy beliefs (the "Foot Care Confidence Scale") and two aspects of actual foot-care behaviour-preventative behaviour and potentially damaging behaviour. Pearson correlation coefficients were then calculated to determine the association between foot-care self-efficacy beliefs and actual reported foot-care behaviour. Multiple analysis of variance was undertaken to compare mean self-efficacy and behaviour subscale scores for those with a history of foot pathology, and those that did not. Results A small positive correlation (r = 0.2, p = 0.05) was found between self-efficacy beliefs and preventative behaviour. There was no association between self-efficacy beliefs and potentially damaging behaviour. There was no difference in self-efficacy beliefs in people that had a history of foot pathology compared to those that did not. Conclusion There is little association between foot-care self-efficacy beliefs and actual foot-care behaviour. The usefulness of measuring foot-care self-efficacy beliefs to assess actual self foot-care behaviour using currently available instruments is limited in people with diabetes and loss of protective sensation. PMID:19192309

  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. 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.

  8. Pilot Trial of a Patient-Specific Cutaneous Electrostimulation Device (MC5-A Calmare®) for Chemotherapy-Induced Peripheral Neuropathy

    PubMed Central

    Smith, Thomas J.; Coyne, Patrick J.; Parker, Gwendolyn L.; Dodson, Patricia; Ramakrishnan, Viswanathan

    2015-01-01

    Context Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and persistent consequence of numerous classes of antineoplastic agents, affecting up to 30%–40% of patients. To date, there is no effective prevention or therapy. An evolving hypothesis for reducing CIPN pain involves direct nerve stimulation to reduce the pain impulse. Objectives To evaluate the impact on CIPN associated with the MC5-A Calmare® therapy device. Methods The MC5-A Calmare® therapy device is designed to generate a patient-specific cutaneous electrostimulation to reduce the abnormal pain intensity. Sixteen patients from one center received one-hour interventions daily over 10 working days. Results Of 18 patients, 16 were evaluable. The mean age of the patients was 58.6 years—four men and 14 women—and the duration of CIPN was three months to eight years. The most common drugs were taxanes, platinums, and bortezomib (Velcade, Millenium Pharmaceuticals, Cambridge MA). At the end of the study (Day 10), a 20% reduction in numeric pain scores was achieved in 15 of 16 patients. The pain score fell 59% from 5.81 ± 1.11 before treatment to 2.38 ± 1.82 at the end of 10 days (P < 0.0001 by paired t-test). A daily treatment benefit was seen with a strong statistically significant difference between the preand post-daily pain scores (P < 0.001). Four patients had their CIPN reduced to zero. A repeated-measures analysis using the scores from all 10 days confirmed these results. No toxicity was seen. Some responses have been durable without maintenance. Conclusion Patient-specific cutaneous electrostimulation with the MC5-A Calmare® device appears to dramatically reduce pain in refractory CIPN patients with no toxicity. Further studies are underway to define the benefit, mechanisms of action, and optimal schedule. PMID:20813492

  9. Defining “occludable” angles in population surveys: drainage angle width, peripheral anterior synechiae, and glaucomatous optic neuropathy in east Asian people

    PubMed Central

    Foster, P J; Aung, T; Nolan, W P; Machin, D; Baasanhu, J; Khaw, P T; Alsbirk, P-H; Lee, P S; Seah, S K L; Johnson, G J

    2004-01-01

    Background/aim: A current consensus in epidemiological studies of primary angle closure (PAC) is to diagnose the condition only if the posterior (usually pigmented) trabecular meshwork is seen for less than 90° of the angle circumference, termed an “occludable angle.” The authors sought to assess the validity of this epidemiological classification by exploring the relation between drainage angle width, peripheral anterior synechiae (PAS) and glaucomatous optic neuropathy (GON). Methods: 918 Mongolians and 995 Chinese Singaporeans, both groups aged 40 years and older were examined in two population based surveys. Gonioscopic angle width was graded in five categories (0 = closed to 4 = wide open) according the scheme described by Shaffer. Cases with secondary PAS were excluded. Results: The rate of PAS was between 0.3% and 1.7% in people with wide angles (grades 3 and 4). In those with grade 2 angles, PAS were seen in between 8% of eyes. In eyes with grade 1 angles, the rate rose to 17% in Chinese Singaporeans, and 31% in Mongolians. The odds of PAS were higher in people with narrower angles. However, there was a greater absolute number of people with PAS whose drainage angles were classified as “not occludable” than those classified “occludable.” Conclusions: The traditional view that primary angle closure becomes a significant possibility in drainage angles of ⩽ grade 2 (approximately 20°) is valid in east Asians. The definition of an “occludable” angle examined here excludes many people with PAS. This probably serves to underemphasise the role of PAC in population surveys of glaucoma prevalence in Asian people. PMID:15031161

  10. Quantitative Sensory Analysis of Peripheral Neuropathy Produced by Colorectal Cancer and its Exacerbation by Cumulative Dose of Oxaliplatin Chemotherapy

    PubMed Central

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

    2014-01-01

    The goal in this study was to determine the impact of colorectal cancer and cumulative chemotherapeutic dose on sensory function to gain mechanistic insight to the subtypes of primary afferent fibers damaged by chemotherapy. Patients with colorectal cancer underwent quantitative sensory testing (QST) before and then prior to each cycle of oxaliplatin. These data were compared to that from age- and sex-matched healthy volunteers. The patients showed significant subclinical deficits in sensory function prior to any therapy compared to healthy volunteers. Sensory deficits became more pronounced in patients with chemotherapy. Sensory deficits were most pronounced for modalities mediated by large Aβ myelinated fibers and unmyelinated C fibers whereas those modalities of sensation conveyed by thinly myelinated Aδ fibers appeared showed less sensitivity 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 re-tested 6 to 12 months following chemotherapy showed the most numbness and pain as well as the most pronounced sensory deficits. The pattern of effects on sensory function has clear mechanistic implications for the fibers types that are vulnerable to the toxicity of chemotherapy. PMID:25183707

  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. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. Neuromuscular ultrasound in common entrapment neuropathies.

    PubMed

    Cartwright, Michael S; Walker, Francis O

    2013-11-01

    Neuromuscular ultrasound involves the use of high-resolution ultrasound to image the peripheral nervous system of patients with suspected neuromuscular diseases. It complements electrodiagnostic studies well by providing anatomic information regarding nerves, muscles, vessels, tendons, ligaments, bones, and other structures that cannot be obtained with nerve conduction studies and electromyography. Neuromuscular ultrasound has been studied extensively over the past 10 years and has been used most often in the assessment of entrapment neuropathies. This review focuses on the use of neuromuscular ultrasound in 4 of the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow and wrist, and fibular neuropathy at the knee.

  19. Exercise as Therapy for Diabetic and Prediabetic Neuropathy.

    PubMed

    Singleton, J Robinson; Smith, A Gordon; Marcus, Robin L

    2015-12-01

    Length-dependent neuropathy is the most common and costly complication of diabetes and frequently causes injury primarily to small-diameter cutaneous nociceptive fibers. Not only persistent hyperglycemia but also metabolic, endocrine, and inflammatory effects of obesity and dyslipidemia appear to play an important role in the development of diabetic neuropathy. Rational therapies aimed at direct control of glucose or its increased entry into the polyol pathway, oxidative or nitrosative stress, advanced glycation end product formation or signaling, microvascular ischemia, or adipocyte-derived toxicity have each failed in human trials of diabetic neuropathy. Aerobic exercise produces salutary effects in many of these pathogenic pathways simultaneously and, in both animal models and human trials, has been shown to improve symptoms of neuropathy and promote re-growth of cutaneous small-diameter fibers. Behavioral reduction in periods of seated, awake inactivity produces multimodal metabolic benefits similar to exercise, and the two strategies when combined may offer sustained benefit to peripheral nerve function. PMID:26538074

  20. Entrapment neuropathies in diabetes mellitus

    PubMed Central

    Rota, Eugenia; Morelli, Nicola

    2016-01-01

    Neuropathy is a common complication of diabetes mellitus (DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies (EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM, particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features.

  1. Entrapment neuropathies in diabetes mellitus

    PubMed Central

    Rota, Eugenia; Morelli, Nicola

    2016-01-01

    Neuropathy is a common complication of diabetes mellitus (DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies (EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM, particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features. PMID:27660694

  2. Entrapment neuropathies in diabetes mellitus.

    PubMed

    Rota, Eugenia; Morelli, Nicola

    2016-09-15

    Neuropathy is a common complication of diabetes mellitus (DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies (EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM, particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features.

  3. Entrapment neuropathies in diabetes mellitus.

    PubMed

    Rota, Eugenia; Morelli, Nicola

    2016-09-15

    Neuropathy is a common complication of diabetes mellitus (DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies (EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM, particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features. PMID:27660694

  4. 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

  5. Chemotherapy-induced pain and neuropathy: a prospective study in patients treated with adjuvant oxaliplatin or docetaxel.

    PubMed

    Ventzel, Lise; Jensen, Anders B; Jensen, Anni R; Jensen, Troels S; Finnerup, Nanna B

    2016-03-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer therapy. This study evaluates symptoms of CIPN and CIPN-related pain and its influence on psychological functioning and potential predictors of chronic CIPN and pain. In this large prospective questionnaire study, 174 patients receiving adjuvant oxaliplatin or docetaxel were consecutively included. Patients were asked to complete a questionnaire with validated questions on peripheral neuropathy, pain, anxiety and depression, and quality of life at baseline, after the first cycle, halfway through therapy, and 1 year after baseline. Chronic CIPN symptoms (tingling and/or numbness) in the feet at 1-year follow-up were present in 63.6% of patients without preexisting neuropathy in the oxaliplatin group and in 44.8% in the docetaxel group, whereas pain in hands and feet was found in 31.3% and 35.1%, respectively. Both groups had significantly different pain profiles, and persistent pain in the docetaxel group was found to have effect on psychological function. Cumulative dose predicted oxaliplatin-induced neuropathy (P = 0.004), whereas endocrine therapy predicted peripheral pain in the docetaxel group (P = 0.04). There are important differences in acute neuropathic symptoms and chronic pain profiles in patients after oxaliplatin and docetaxel treatment. It is, however, important to recognize that chronic peripheral pain may be unrelated to neuropathy and can be caused by concomitant treatments. Future studies should focus on characterizing and distinguishing CIPN-related pain from other types of pain to determine the best outcome measures for trials on prevention or relief. PMID:26529271

  6. Gene therapy for peripheral nervous system diseases.

    PubMed

    Federici, Thais; Boulis, Nicholas

    2007-08-01

    Peripheral nerve diseases, also known as peripheral neuropathies, affect 15-20 million of Americans and diabetic neuropathy is the most common condition. Currently, the treatment of peripheral neuropathies is more focused on managing pain rather than providing permissive conditions for regeneration. Despite advances in microsurgical techniques, including nerve grafting and reanastomosis, axonal regeneration after peripheral nerve injury remains suboptimal. Also, no satisfactory treatments are available at this time for peripheral neurodegeneration occurring in motor neuron diseases (MND), including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Peripheral nerves have the inherent capacity of regeneration. Gene therapy strategies focused on neuroprotection may help optimizing axonal regrowth. A better understanding of the cellular and molecular events involved in axonal degeneration and regeneration have helped researchers to identify targets for intervention. This review summarizes the current state on the clinical experience as well as gene therapy strategies for peripheral neuropathies, including MND, peripheral nerve injury, neuropathic pain, and diabetic neuropathy.

  7. Diabetic neuropathy part 1: overview and symmetric phenotypes.

    PubMed

    Pasnoor, Mamatha; Dimachkie, Mazen M; Kluding, Patricia; Barohn, Richard J

    2013-05-01

    Diabetes is the most common cause of neuropathy in United States and neuropathies are the most common complication of diabetes mellitus, affecting up to 50% of patients with type 1 and type 2 diabetes mellitus. Symptoms usually include numbness, tingling, pain, and weakness. Dizziness with postural changes can be seen with autonomic neuropathy. Metabolic, vascular, and immune theories have been proposed for the pathogenesis of diabetic neuropathy. Axonal damage and segmental demyelination can be seen with diabetic neuropathies. Management of diabetic neuropathy should begin at the initial diagnosis of diabetes and mainly requires tight and stable glycemic control.

  8. Treatment induced diabetic neuropathy– a reversible painful autonomic neuropathy

    PubMed Central

    Gibbons, Christopher H; Freeman, Roy

    2011-01-01

    Objective To describe the natural history, clinical, neurophysiological and histological features and outcomes of diabetic patients presenting with acute painful neuropathy associated with glycemic control, also referred to as ‘insulin neuritis’. Methods Sixteen subjects, presenting with acute painful neuropathy had neurological and retinal examinations, laboratory studies, autonomic testing and pain assessments over 18 months. Eight subjects had skin biopsies for evaluation of intra-epidermal nerve fiber density. Results All subjects developed severe pain within 8 weeks of intensive glucose control. There was a high prevalence of autonomic cardiovascular, gastrointestinal, genitourinary, and sudomotor symptoms in all subjects. Orthostatic hypotension and parasympathetic dysfunction were seen in 69% of subjects. Retinopathy worsened in all subjects. Reduced intra-epidermal nerve fiber density (IENFD) was seen in all tested subjects. After 18 months of glycemic control, there were substantial improvements in pain, autonomic symptoms, autonomic test results and IENFD. Greater improvements were seen after 18 months in type 1 vs. type 2 diabetic subjects in autonomic symptoms (cardiovascular p<0.01; gastrointestinal p<0.01; genitourinary p<0.01) and autonomic function tests (p<0.01, sympathetic and parasympathetic function tests). Interpretation Treatment induced neuropathy is characterized by acute, severe pain, peripheral nerve degeneration and autonomic dysfunction after intensive glycemic control. The neuropathy occurred in parallel with worsening diabetic retinopathy suggesting a common underlying pathophysiological mechanism. Clinical features and objective measures of small myelinated and unmyelinated nerve fibers can improve in these diabetic patients despite a prolonged history of poor glucose control, with greater improvement seen in patients with type 1 diabetes. PMID:20437589

  9. Lack of association of the CEP72 rs924607 TT genotype with vincristine-related peripheral neuropathy during the early phase of pediatric acute lymphoblastic leukemia treatment in a Spanish population.

    PubMed

    Gutierrez-Camino, Angela; Martin-Guerrero, Idoia; Lopez-Lopez, Elixabet; Echebarria-Barona, Aizpea; Zabalza, Iñaki; Ruiz, Irune; Guerra-Merino, Isabel; Garcia-Orad, Africa

    2016-02-01

    Vincristine is a component of acute lymphoblastic leukemia (ALL) treatment with the potential to induce peripheral neuropathy. Recently, the CEP72 rs924607 TT genotype was found to be associated with vincristine-induced toxicity during the continuation phase in pediatric ALL patients treated on the Total XIIIB and COG AALL0433 protocols at St Jude Children's Research Hospital and Children's Oncology Group. This finding could provide a base for safer dosing of vincristine. Nevertheless, there are variations in vincristine regimens among ALL treatment protocols and phases in different populations. Therefore, the aim of this study was to determine whether the CEP72 rs924607 TT genotype is a useful marker of vincristine neuropathy during induction therapy among Spanish children with B-ALL treated on the LAL-SHOP protocols. No association was found between neurotoxicity during the induction phase and the rs924607 TT genotype. This lack of association could be because of population differences and/or differences in neurotoxicity etiology between induction and continuation phases of treatment. PMID:26618658

  10. 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

  11. Molecular basis of hereditary neuropathies.

    PubMed

    Chance, P F

    2001-05-01

    Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B) and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (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 or MPZ) gene. The molecular defect in CMT1C is unknown. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy, also of undetermined cause. Forms of CMT2 map to chromosome 1p36 (CMT2A), chromosome 3p (CMT2B), chromosome 7p (CMT2D), and to chromosome 8p21 (CMT2E). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset, demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene or the P0 gene and shares considerable clinical and pathologic features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosomes 8q, 10q, and 11q. Hereditary neuralgic amyotrophy (familial brachial plexus neuropathy) is an autosomal dominant disorder causing painful, recurrent brachial plexopathies

  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. 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

  14. [SUPRASCAPULAR NEUROPATHY].

    PubMed

    Massenet, V; Crielaard, J M

    2016-05-01

    Supra-scapular nerve (SSN) damage is a rare, but classical diagnosis that can often be overlooked since the nonspecific clinical history and examination commonly lead to the misdiagnosis of another shoulder disorder. This article details the etiopathology, the patients at risk, the reasons for consultation and the clinical aspects of suprascapular neuropathy; it also outlines its diagnostic and therapeutic approaches. PMID:27337843

  15. 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

  16. 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

  17. Dizziness symptom severity and impact on daily living as perceived by patients suffering from peripheral vestibular disorder.

    PubMed

    Mendel, B; Bergenius, J; Langius, A

    1999-08-01

    The purpose of this study was to describe quality-of-life aspects in a group of patients (n = 99) suffering from peripheral vestibular disorder, using three different self-rated instruments, the Vertigo Symptom Scale (VSS), the Vertigo Handicap Questionnaire (VHQ) and the Sickness Impact Profile (SIP). The results showed that the type of dizziness that most influenced the quality-of-life aspects were: frequent short- or long-term dizziness, nausea, and the feeling that the ground was distant or as though the patient were walking on clouds. However, several of the impairments in daily life were neither related to the disease itself nor the demographic data. This verifies the necessity of investigating other factors such as personality and coping capacity. The results of this study also demonstrate the patients' need of psychosocial support. A comprehensive assessment and evaluation is important in order to identify each patient's needs.

  18. 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

  19. 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

  20. Genetic spectrum of hereditary neuropathies with onset in the first year of life

    PubMed Central

    Baets, Jonathan; Deconinck, Tine; De Vriendt, Els; Zimoń, Magdalena; Yperzeele, Laetitia; Van Hoorenbeeck, Kim; Peeters, Kristien; Spiegel, Ronen; Parman, Yesim; Ceulemans, Berten; Van Bogaert, Patrick; Pou-Serradell, Adolf; Bernert, Günther; Dinopoulos, Argirios; Auer-Grumbach, Michaela; Sallinen, Satu-Leena; Fabrizi, Gian Maria; Pauly, Fernand; Van den Bergh, Peter; Bilir, Birdal; Battaloglu, Esra; Madrid, Ricardo E.; Kabzińska, Dagmara; Kochanski, Andrzej; Topaloglu, Haluk; Miller, Geoffrey; Jordanova, Albena; Timmerman, Vincent

    2011-01-01

    Early onset hereditary motor and sensory neuropathies are rare disorders encompassing congenital hypomyelinating neuropathy with disease onset in the direct post-natal period and Dejerine–Sottas neuropathy starting in infancy. The clinical spectrum, however, reaches beyond the boundaries of these two historically defined disease entities. De novo dominant mutations in PMP22, MPZ and EGR2 are known to be a typical cause of very early onset hereditary neuropathies. In addition, mutations in several other dominant and recessive genes for Charcot–Marie–Tooth disease may lead to similar phenotypes. To estimate mutation frequencies and to gain detailed insights into the genetic and phenotypic heterogeneity of early onset hereditary neuropathies, we selected a heterogeneous cohort of 77 unrelated patients who presented with symptoms of peripheral neuropathy within the first year of life. The majority of these patients were isolated in their family. We performed systematic mutation screening by means of direct sequencing of the coding regions of 11 genes: MFN2, PMP22, MPZ, EGR2, GDAP1, NEFL, FGD4, MTMR2, PRX, SBF2 and SH3TC2. In addition, screening for the Charcot–Marie–Tooth type 1A duplication on chromosome 17p11.2-12 was performed. In 35 patients (45%), mutations were identified. Mutations in MPZ, PMP22 and EGR2 were found most frequently in patients presenting with early hypotonia and breathing difficulties. The recessive genes FGD4, PRX, MTMR2, SBF2, SH3TC2 and GDAP1 were mutated in patients presenting with early foot deformities and variable delay in motor milestones after an uneventful neonatal period. Several patients displaying congenital foot deformities but an otherwise normal early development carried the Charcot–Marie–Tooth type 1A duplication. This study clearly illustrates the genetic heterogeneity underlying hereditary neuropathies with infantile onset. PMID:21840889

  1. Genetic spectrum of hereditary neuropathies with onset in the first year of life.

    PubMed

    Baets, Jonathan; Deconinck, Tine; De Vriendt, Els; Zimoń, Magdalena; Yperzeele, Laetitia; Van Hoorenbeeck, Kim; Peeters, Kristien; Spiegel, Ronen; Parman, Yesim; Ceulemans, Berten; Van Bogaert, Patrick; Pou-Serradell, Adolf; Bernert, Günther; Dinopoulos, Argirios; Auer-Grumbach, Michaela; Sallinen, Satu-Leena; Fabrizi, Gian Maria; Pauly, Fernand; Van den Bergh, Peter; Bilir, Birdal; Battaloglu, Esra; Madrid, Ricardo E; Kabzińska, Dagmara; Kochanski, Andrzej; Topaloglu, Haluk; Miller, Geoffrey; Jordanova, Albena; Timmerman, Vincent; De Jonghe, Peter

    2011-09-01

    Early onset hereditary motor and sensory neuropathies are rare disorders encompassing congenital hypomyelinating neuropathy with disease onset in the direct post-natal period and Dejerine-Sottas neuropathy starting in infancy. The clinical spectrum, however, reaches beyond the boundaries of these two historically defined disease entities. De novo dominant mutations in PMP22, MPZ and EGR2 are known to be a typical cause of very early onset hereditary neuropathies. In addition, mutations in several other dominant and recessive genes for Charcot-Marie-Tooth disease may lead to similar phenotypes. To estimate mutation frequencies and to gain detailed insights into the genetic and phenotypic heterogeneity of early onset hereditary neuropathies, we selected a heterogeneous cohort of 77 unrelated patients who presented with symptoms of peripheral neuropathy within the first year of life. The majority of these patients were isolated in their family. We performed systematic mutation screening by means of direct sequencing of the coding regions of 11 genes: MFN2, PMP22, MPZ, EGR2, GDAP1, NEFL, FGD4, MTMR2, PRX, SBF2 and SH3TC2. In addition, screening for the Charcot-Marie-Tooth type 1A duplication on chromosome 17p11.2-12 was performed. In 35 patients (45%), mutations were identified. Mutations in MPZ, PMP22 and EGR2 were found most frequently in patients presenting with early hypotonia and breathing difficulties. The recessive genes FGD4, PRX, MTMR2, SBF2, SH3TC2 and GDAP1 were mutated in patients presenting with early foot deformities and variable delay in motor milestones after an uneventful neonatal period. Several patients displaying congenital foot deformities but an otherwise normal early development carried the Charcot-Marie-Tooth type 1A duplication. This study clearly illustrates the genetic heterogeneity underlying hereditary neuropathies with infantile onset. PMID:21840889

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. 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

  6. 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

  7. 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

  8. Preliminary crystallographic analysis of the N-terminal PDZ-like domain of periaxin, an abundant peripheral nerve protein linked to human neuropathies

    PubMed Central

    Han, Huijong; Kursula, Petri

    2013-01-01

    Periaxin (PRX) is an abundant protein in peripheral nerves and contains a predicted PDZ-like domain at its N-terminus. The large isoform, L-PRX, is required for the maintenance of myelin in the peripheral nervous system and its defects cause neurological disease. Here, the human periaxin PDZ-like domain was crystallized and X-ray diffraction data were collected to 2.85 Å resolution using synchrotron radiation. The crystal belonged to the primitive hexagonal space group P3121 or P3221, with unit-cell parameters a = b = 80.6, c = 81.0 Å, γ = 120° and either two or three molecules in the asymmetric unit. The structure of PRX will shed light on its poorly characterized function in the nervous system. PMID:23832213

  9. DIABETIC NEUROPATHY PART 1: OVERVIEW AND SYMMETRIC PHENOTYPES

    PubMed Central

    Pasnoor, Mamatha; Dimachkie, Mazen M.; Kluding, Patricia; Barohn, Richard J.

    2014-01-01

    Diabetes is the most common cause of neuropathy in US and neuropathies are the most common complication of diabetes mellitus affecting up to 50% of patients with type 1 and type 2 diabetes mellitus. Various types of neuropathies can be associated with diabetes mellitus.1 Symptoms usually include numbness, tingling, pain and weakness. Dizziness with postural changes can be seen with autonomic neuropathy. Metabolic, vascular and immune theories have been proposed for the pathogenesis of diabetic neuropathy. Pathologically axonal damage and segmental demyelination can be seen with diabetic neuropathies. Management of diabetic neuropathy should begin at the initial diagnosis of diabetes and mainly requires tight and stable glycemic control. Many medications are available for the treatment of neuropathic pain. PMID:23642717

  10. 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

  11. 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.

  12. Diabetic neuropathy part 2: proximal and asymmetric phenotypes.

    PubMed

    Pasnoor, Mamatha; Dimachkie, Mazen M; Barohn, Richard J

    2013-05-01

    Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is the most common type of diabetic neuropathy, many other subtypes have been defined since the 1800s, including proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most 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 however are controversial.

  13. 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 ...

  14. 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

  15. 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

  16. Sports and peripheral nerve injury.

    PubMed

    Hirasawa, Y; Sakakida, K

    1983-01-01

    Peripheral nerve injury is one of the serious complications of athletic injuries; however, they have rarely been reported. According to the report by Takazawa et al., there were only 28 cases of peripheral nerve injury among 9,550 cases of sports injuries which had been treated in the previous 5 years at the clinic of the Japanese Athletic Association. The authors have encountered 1,167 cases of peripheral nerve injury during the past 18 years. Sixty-six of these cases were related to sports (5.7%). The nerves most frequently involved were: brachial plexus, radial nerve, ulnar, peroneal, and axillary nerves (in their order of frequency). The most common causes of such injuries were mountain climbing, gymnastics, and baseball. More often, peripheral nerve injury seemed to be caused by continuous compression and repeated trauma to the involved nerve. Usually it appeared as an entrapment neuropathy and the symptoms could be improved by conservative treatment. Some of the cases were complicated by fractures and surgical exploration became necessary. Results of treatment produced excellent to good improvement in 87.9% of the cases. With regard to compartment syndrome, the authors stress the importance of early and precise diagnosis and a fasciotomy.

  17. 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

  18. 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

  19. 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.

  20. Characterization of cannabinoid-induced relief of neuropathic pain in a rat model of cisplatin-induced neuropathy.

    PubMed

    Vera, Gema; Cabezos, Pablo Antonio; Martín, María Isabel; Abalo, Raquel

    2013-04-01

    Clinical use of antineoplastic drugs is associated with the development of numerous adverse effects that many patients find intolerable, including peripheral neuropathy. Cannabinoids have relieved neuropathic pain in different animal models. But their therapeutic activities could be affected by their psychoactive properties. The aim of this work was to determine the effect of cannabinoids in cisplatin-evoked neuropathy. For this purpose, the non-selective agonist WIN 55,212-2 (WIN), the CB1-selective agonist ACEA or the CB2-selective agonist JWH133 (or their vehicle) was either systemically administered at a non-psychoactive dose or locally injected in cisplatin-treated rats. Selective CB1 and CB2 cannabinoid antagonists (AM251 and SR144528, respectively) were used to characterize cannabinoid effects. Cisplatin-treated rats showed mechanical allodynia but not thermal hyperalgesia. Cannabinoid agonists alleviated mechanical allodynia. This effect was mediated by both CB1 and CB2 cannabinoid receptors when the cannabinoid was systemically applied. At the dose used, cannabinoid agonists had no psychoactive effect. The local effect of the drug involved the activation of peripheral CB1 receptors whereas involvement of CB2 receptors was less clear. In a rat model of cisplatin-induced neuropathy, cannabinoids have an antinociceptive effect, but the cannabinoid receptors involved could be different depending on the route of administration. Non-psychoactive doses of cannabinoid agonists are capable of alleviating the signs of peripheral neuropathy when systemically applied. Interestingly, local administration of selective CB1 agonists or systemic administration of CB2 agonists, which are non-psychoactive, may serve as new therapeutic alternatives for symptom management in painful neuropathy associated with cisplatin treatment. PMID:23454533

  1. Pupillary signs in diabetic autonomic neuropathy.

    PubMed Central

    Smith, S E; Smith, S A; Brown, P M; Fox, C; Sönksen, P H

    1978-01-01

    Pupillary function was investigated in 36 insulin-dependent diabetics and 36 controls matched for age and sex. About half of the diabetics had evidence of peripheral somatic or autonomic neuropathy, or both. The diabetic patients had abnormally small pupil diameters in the dark and less fluctuation in pupil size (hippus) during continuous illumination than the controls. They also had reduced reflex responses to light flashes of an intensity adjusted for individual retinal sensitivities. The pupillary findings were compared with results of five tests of cardiovascular function and five tests of peripheral sensory and motor nerve function. Almost all the patients with autonomic neuropathy had pupillary signs, which we therefore conclude are a common manifestation of diabetic autonomic neuropathy. PMID:709128

  2. Sjögren Syndrome-Associated Small Fiber Neuropathy

    PubMed Central

    Sène, Damien; Cacoub, Patrice; Authier, François-Jérôme; Haroche, Julien; Créange, Alain; Saadoun, David; Amoura, Zahir; Guillausseau, Pierre-Jean; Lefaucheur, Jean-Pascal

    2013-01-01

    Abstract We conducted the current study to analyze the clinical, immunologic, and neurophysiologic features of primary Sjögren syndrome (pSS)-associated sensory small fiber neuropathies (SFNs). Forty consecutive pSS patients with SFN were included. SFN was defined by the presence of suggestive sensory painful symptoms with normal nerve conduction studies and abnormal neurophysiologic tests for small nerve fibers or a low intraepidermal nerve fiber density at skin biopsy. Included patients were compared to 100 pSS patients without peripheral neuropathy. SFN patients were mainly female (92.5%). Age at pSS diagnosis was 55.3 ± 13.1 years, and at SFN diagnosis, 58.9 ± 11.8 years, with a median time to SFN diagnosis after symptom onset of 3.4 years. Clinical symptoms included burning pains (90%), numbness (87.5%), tingling (82.5%), pins and needles (72.5%), electric discharges (70%), and allodynia (55%). Dysautonomia included vasomotor symptoms (66%) and hyperhidrosis (47%). Abnormal neurophysiologic tests included laser evoked potentials (97.5%), thermal quantitative sensory testing (67.5%), and sympathetic skin reflex (40%). A skin biopsy revealed low intraepidermal nerve fiber density in 76% of the 17 tested patients. Compared to the 100 pSS patients without peripheral neuropathy, the 40 pSS-SFN patients were older at pSS diagnosis (55.3 ± 13.1 vs. 49.5 ± 14.9 yr; p = 0.03), and more often had xerostomia (97.5% vs. 81%; p = 0.01) and arthralgia (82.5% vs. 65.0%; p = 0.04). Immunologically, they were characterized by a lower prevalence of serum B-cell activation markers, that is, antinuclear antibodies (65% vs. 85%; p = 0.01), anti-SSA (42.5% vs. 71%; p = 0.002), and anti-SSB (17.5% vs. 39%; p = 0.017); rheumatoid factor (32.5% vs. 66%; p = 0.0005); and hypergammaglobulinemia (35% vs. 62%; p = 0.005). In conclusion, we report the main features of SFN in patients with pSS, the first such study to our knowledge. Our results show that patients with p

  3. North America and South America (NA-SA) neuropathy project.

    PubMed

    Pasnoor, Mamatha; Nascimento, Osvaldo J M; Trivedi, Jaya; Wolfe, Gil I; Nations, Sharon; Herbelin, Laura; de Freitas, M G; Quintanilha, Giseli; Khan, Saud; Dimachkie, Mazen; Barohn, Richard

    2013-08-01

    Peripheral neuropathy is a common neurological disorder. There may be important differences and similarities in the diagnosis of peripheral neuropathy between North America (NA) and South America (SA). Neuromuscular databases were searched for neuropathy diagnosis at two North American sites, University of Kansas Medical Center and University of Texas Southwestern Medical Center, and one South American site, Federal Fluminense University in Brazil. All patients were included into one of the six major categories: immune-mediated, diabetic, hereditary, infectious/inflammatory, systemic/metabolic/toxic (not diabetic) and cryptogenic. A comparison of the number of patients in each category was made between North America and South America databases. Total number of cases in North America was 1090 and in South America was 1034 [immune-mediated: NA 215 (19.7%), SA 191 (18%); diabetic: NA 148 (13.5%), SA 236 (23%); hereditary: NA 292 (26.7%), SA 103 (10%); infectious/inflammatory: NA 53 (4.8%), SA 141 (14%); systemic/metabolic/toxic: NA 71 (6.5%), SA 124 (12%); cryptogenic: NA 311 (28.5%), SA 239 (23%)]. Some specific neuropathy comparisons were hereditary neuropathies [Charcot-Marie-Tooth (CMT) cases] in NA 246/292 (84.2%) and SA 60/103 (58%); familial amyloid neuropathy in SA 31/103 (30%) and none in NA. Among infectious neuropathies, cases of human T-lymphotropic virus type 1 (HTLV-1) neuropathy in SA were 36/141(25%), Chagas disease in SA were 13/141(9%) and none for either in NA; cases of neuropathy due to leprosy in NA were 26/53 (49%) and in SA were 39/141(28%). South American tertiary care centers are more likely to see patients with infectious, diabetic and hereditary disorders such as familial amyloid neuropathies. North American tertiary centers are more likely to see patients with CMT. Immune neuropathies and cryptogenic neuropathies were seen equally in North America and South America.

  4. Duration of disease, neuropathic symptoms, and plantar sensitivity in patients with diabetes with and without previous plantar ulceration.

    PubMed

    de Almeida Bacarin, Tatiana; Akashi, Paula M H; de C N Sacco, Prof Isabel

    2008-02-01

     This study compared the duration of disease, the prevalence of neuropathy symptoms, and plantar insensitivity among subjects with diabetic neuropathy, with and without previous history of plantar ulcers, to a nondiabetic group of subjects. Correlations were made between the neuropathic symptoms observed and the results of sensory tests. Thermal and tactile sensitivities and sensitive chronaxie were measured in the control group (CG, n = 19), a diabetic neuropathic group (DG, n = 16), and a diabetic neuropathic group with previous history of plantar ulceration (UDG, n = 9). Plantar sensitivity was investigated in 5 areas of the plantar surface of both feet: heel, midfoot, lateral forefoot, medial forefoot, and hallux. The neuropathy symptoms were investigated using the Michigan Neuropathy Screening Instrument (MNSI). The neuropathic groups did not differ in duration of diabetes onset (DG = 13 years ± 8; UDG = 14 years ± 5; P = 0.243) and they presented similar mean for symptoms according to MNSI score (DG = 6.94 ± 1.81; UDG = 6.78 ± 2.44; P = 0.352). The frequency of subjects with abnormal sensitivity was higher in UDG. The MNSI showed moderate correlation with tactile sensitivity (r <-0.42, P <0.05). Patients with diabetic neuropathy and an ulcer had decreased sensitivity in their feet. The symptoms may indicate loss of sensation, but symptoms alone are not able to differentiate between neuropathic subjects with different progressions of diabetic peripheral neuropathy (DPN). Duration of diabetes and symptoms did not explain the severity of neuropathy in people with a diabetic ulcer.

  5. Suprascapular neuropathy in pitchers.

    PubMed

    Ringel, S P; Treihaft, M; Carry, M; Fisher, R; Jacobs, P

    1990-01-01

    The clinical features and preoperative and postoperative electrodiagnostic studies were reviewed in two professional pitchers with a suprascapular neuropathy. These studies demonstrate that denervation of the infraspinatus and/or supraspinatus muscle is not always due to entrapment of the nerve at the suprascapular or spinoglenoid notches, as is often proposed. Similar studies in healthy pitchers during spring training and again at midseason demonstrate that slowing of suprascapular nerve conduction is detectable in some cases as the season progresses. Sagittal sections of a cadaver with the arm fixed in the acceleration phase of the pitching motion demonstrate five possible sites of trauma to the suprascapular nerve. Mechanisms proposed to explain these progressive, but potentially reversible, changes include consideration of biomechanical factors as well as anatomical features. An alternative hypothesis to nerve trauma that explains this symptom complex is intimal damage to the axillary or suprascapular artery and subsequent production of microemboli which become trapped in the suprascapular nerve vasa nervorum.

  6. 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

  7. 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.

  8. Inhibiting TRPA1 ion channel reduces loss of cutaneous nerve fiber function in diabetic animals: sustained activation of the TRPA1 channel contributes to the pathogenesis of peripheral diabetic neuropathy.

    PubMed

    Koivisto, Ari; Hukkanen, Mika; Saarnilehto, Marja; Chapman, Hugh; Kuokkanen, Katja; Wei, Hong; Viisanen, Hanna; Akerman, Karl E; Lindstedt, Ken; Pertovaara, Antti

    2012-01-01

    Peripheral diabetic neuropathy (PDN) is a devastating complication of diabetes mellitus (DM). Here we test the hypothesis that the transient receptor potential ankyrin 1 (TRPA1) ion channel on primary afferent nerve fibers is involved in the pathogenesis of PDN, due to sustained activation by reactive compounds generated in DM. DM was induced by streptozotocin in rats that were treated daily for 28 days with a TRPA1 channel antagonist (Chembridge-5861528) or vehicle. Laser Doppler flow method was used for assessing axon reflex induced by intraplantar injection of a TRPA1 channel agonist (cinnamaldehyde) and immunohistochemistry to assess substance P-like innervation of the skin. In vitro calcium imaging and patch clamp were used to assess whether endogenous TRPA1 agonists (4-hydroxynonenal and methylglyoxal) generated in DM induce sustained activation of the TRPA1 channel. Axon reflex induced by a TRPA1 channel agonist in the plantar skin was suppressed and the number of substance P-like immunoreactive nerve fibers was decreased 4 weeks after induction of DM. Prolonged treatment with Chembridge-5861528 reduced the DM-induced attenuation of the cutaneous axon reflex and loss of substance P-like immunoreactive nerve fibers. Moreover, in vitro calcium imaging and patch clamp results indicated that reactive compounds generated in DM (4-hydroxynonenal and methylglyoxal) produced sustained activations of the TRPA1 channel, a prerequisite for adverse long-term effects. The results indicate that the TRPA1 channel exerts an important role in the pathogenesis of PDN. Blocking the TRPA1 channel provides a selective disease-modifying treatment of PDN. PMID:22133672

  9. 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

  10. Persisting nutritional neuropathy amongst former war prisoners.

    PubMed Central

    Gill, G V; Bell, D R

    1982-01-01

    Of 898 former Far East prisoners of war, assessed between 1968 and 1981, 49 (5.5%) had evidence of persisting symptomatic neurological disease dating back to their periods of malnutrition in captivity. The commonest syndromes were peripheral neuropathy (often of "burning foot" type), optic atrophy, and sensori-neural deafness. Though nutritional neuropathies disappeared soon after release in most ex-Far East prisoners of war, in some they have persisted up to 36 years since exposure to the nutritional insult. PMID:6292369

  11. 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

  12. Relationships between presynaptic inhibition and static postural sway in subjects with and without diabetic neuropathy.

    PubMed

    Chun, Jihyun; Hong, Junggi

    2015-09-01

    [Purpose] Diabetic peripheral neuropathy can often lead to balance impairment. The spinal reflex is a mechanism that is reportedly important for balance, but it has not been investigated in diabetic peripheral neuropathy patients. Moreover, inhibitory or facilitatory behavior of the spinal reflex-known as presynaptic inhibition-is essential for controlling postural sway. The purpose of this study was to compare the differences in as presynaptic inhibition and balance in subjects with and without diabetic peripheral neuropathy to determine the influence of presynaptic inhibition on balance in diabetic peripheral neuropathy patients. [Subjects and Methods] Presynaptic inhibition and postural sway were tested in eight patients (mean age, 58±6 years) and eight normal subjects (mean age, 59±7 years). The mean percent difference in conditioned reflex amplitude relative to the unconditioned reflex amplitude was assessed to calculate as presynaptic inhibition. The single-leg balance index was measured using a computerized balance-measuring device. [Results] The diabetic peripheral neuropathy group showed lower presynaptic inhibition (47±30% vs. 75±22%) and decreased balance (0.65±0.24 vs. 0.38±0.06) as compared with the normal group. No significant correlation was found between as presynaptic inhibition and balance score (R=0.37). [Conclusion] Although the decreased as presynaptic inhibition observed in diabetic peripheral neuropathy patients may suggest central nervous system involvement, further research is necessary to explore the role of presynaptic inhibition in decreased balance in diabetic peripheral neuropathy patients.

  13. [Genetics of neuropathies].

    PubMed

    Gess, B; Schirmacher, A; Young, P

    2013-02-01

    Hereditary neuropathies belong to the most common neurogenetic disorders. They appear mostly as sensory and motor neuropathies but there are also pure sensory, pure motor as well as sensory and autonomic hereditary neuropathies. In clinical practice, knowledge of hereditary neuropathies is important in order to recognize them among polyneuropathies and achieve a successful genetic diagnosis. The molecular genetics of hereditary neuropathies are very heterogeneous with currently more than 40 known disease-causing genes. The 4 most common genes account for almost 90% of the genetically diagnosed hereditary neuropathies. In this review article we provide an overview of the currently known genes and propose a rational genetic work-up protocol of the most common genes.

  14. 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.

  15. 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.

  16. Foot Pad Skin Biopsy in Mouse Models of Hereditary Neuropathy

    PubMed Central

    Dacci, Patrizia; Dina, Giorgia; Cerri, Federica; Previtali, Stefano Carlo; Lopez, Ignazio Diego; Lauria, Giuseppe; Feltri, Maria Laura; Bolino, Alessandra; Comi, Giancarlo; Wrabetz, Lawrence; Quattrini, Angelo

    2010-01-01

    Numerous transgenic and knockout mouse models of human hereditary neuropathies have become available over the past decade. We describe a simple, reproducible, and safe biopsy of mouse skin for histopathological evaluation of the peripheral nervous system (PNS) in models of hereditary neuropathies. We compared the diagnostic outcome between sciatic nerve and dermal nerves found in skin biopsy (SB) from the hind foot. A total of five animal models of different Charcot-Marie-Tooth neuropathies, and one model of congenital muscular dystrophy associated neuropathy were examined. In wild type mice, dermal nerve fibers were readily identified by immunohistochemistry, light, and electron microscopy and they appeared similar to myelinated fibers in sciatic nerve. In mutant mice, SB manifested myelin abnormalities similar to those observed in sciatic nerves, including hypomyelination, onion bulbs, myelin outfolding, redundant loops, and tomacula. In many strains, however, SB showed additional abnormalities—fiber loss, dense neurofilament packing with lower phosphorylation status, and axonal degeneration—undetected in sciatic nerve, possibly because SB samples distal nerves. SB, a reliable technique to investigate peripheral neuropathies in human beings, is also useful to investigate animal models of hereditary neuropathies. Our data indicate that SB may reveal distal axonal pathology in mouse models and permits sequential follow-up of the neuropathy in an individual mouse, thereby reducing the number of mice necessary to document pathology of the PNS. © 2010 Wiley-Liss, Inc. PMID:20878767

  17. Reversible isolated sensory axonal neuropathy due to cobalamin deficiency.

    PubMed

    Dalla Torre, Chiara; Lucchetta, Marta; Cacciavillani, Mario; Campagnolo, Marta; Manara, Renzo; Briani, Chiara

    2012-03-01

    Vitamin B(12) deficiency causes a wide range of hematological, gastrointestinal, and neurological manifestations. The most common neurological complication is subacute combined degeneration, sometimes associated with polyneuropathy. Isolated peripheral neuropathy due to cyanocobalamin deficiency is less frequent, and thus it may be overlooked. We describe 2 patients with isolated sensory axonal neuropathy secondary to vitamin B(12) deficiency who had complete clinical and electrophysiological recovery after cyanocobalamin replacement. Testing for serum vitamin B(12) and its metabolites should be done in any distal symmetric neuropathy.

  18. Somatosensory symptoms in unmedicated de novo patients with idiopathic Parkinson's disease.

    PubMed

    Schindlbeck, Katharina A; Mehl, Arne; Geffe, Sarah; Benik, Steffen; Tütüncü, Serdar; Klostermann, Fabian; Marzinzik, Frank

    2016-03-01

    Parkinson's disease (PD) is a neurodegenerative condition presenting with motor and non-motor symptoms including somatosensory disturbances. As neuropathic syndromes in advanced PD patients are supposed to be due to antiparkinsonian medication, we studied the presence of somatosensory symptoms and peripheral nerve function in drug naïve patients with PD as well as age-matched healthy controls. Somatosensory symptoms and signs were investigated in 39 de novo PD patients and 32 age-matched healthy controls using the modified Toronto Clinical Neuropathy Scale. To elucidate potential underlying mechanisms, peripheral nerve function was analyzed with sensory and motor neurography. About two thirds of de novo diagnosed levodopa naïve PD patients (66.7 %) reported somatosensory symptoms in comparison to one third of the control group (31.2 %) (p = 0.003). The presence of PD (p = 0.017) was a predictive factor for the occurrence of somatosensory symptoms among all participants. In contrast to the significantly higher frequency of somatosensory symptoms in patients with PD compared to controls, neurographically based peripheral nerve function did not differ between the groups. Our results indicate that somatosensory symptoms are a PD feature, which can be found when diagnosed first and independently of dopaminergic treatment. As the electrophysiologically determined peripheral nerve function was not different from that obtained in the control group, somatosensory symptoms are inherent in early PD and may be, at least partially, of central origin. PMID:26392189

  19. Peripheral neuropathy associated with erythrophagocytic lymphohistiocytosis.

    PubMed Central

    Boutin, B; Routon, M C; Rocchiccioli, F; Mayer, M; Leverger, G; Robain, O; Ponsot, G; Arthuis, M

    1988-01-01

    A 12 year old patient who developed clinical, biochemical and histological features of erythrophagocytic lymphohistiocytosis is described. In contrast to previously reported cases, the prominent neurological feature was a subacute sensorimotor polyneuropathy. Sural nerve biopsy showed a marked reduction of myelinated fibres and severe axonal lesions, absence of histiocyte infiltration and deposits of IgM along the epineurium. In addition to the hypertriglyceridaemia previously described in this condition, an elevation of plasma very long-chain fatty acids and phytanic acid was found which suggests a transient impairment of peroxisomal functions. Images PMID:3346698

  20. Periaxin mutations cause recessive Dejerine-Sottas neuropathy.

    PubMed

    Boerkoel, C F; Takashima, H; Stankiewicz, P; Garcia, C A; Leber, S M; Rhee-Morris, L; Lupski, J R

    2001-02-01

    The periaxin gene (PRX) encodes two PDZ-domain proteins, L- and S-periaxin, that are required for maintenance of peripheral nerve myelin. Prx(-/-) mice develop a severe demyelinating peripheral neuropathy, despite apparently normal initial formation of myelin sheaths. We hypothesized that mutations in PRX could cause human peripheral myelinopathies. In accordance with this, we identified three unrelated Dejerine-Sottas neuropathy patients with recessive PRX mutations-two with compound heterozygous nonsense and frameshift mutations, and one with a homozygous frameshift mutation. We mapped PRX to 19q13.13-13.2, a region recently associated with a severe autosomal recessive demyelinating neuropathy in a Lebanese family (Delague et al. 2000) and syntenic to the location of Prx on murine chromosome 7 (Gillespie et al. 1997). PMID:11133365

  1. Schwann Cell Expression of PLP1 but Not DM20 Is Necessary to Prevent Neuropathy

    PubMed Central

    Shy, Michael E.; Hobson, Grace; Jain, Manisha; Boespflug-Tanguy, Odile; Garbern, James; Sperle, Karen; Li, Wen; Gow, Alex; Rodriguez, Diana; Bertini, Enrico; Mancias, Pedro; Krajewski, Karen; Lewis, Richard; Kamholz, John

    2016-01-01

    Proteolipid protein (PLP1) and its alternatively spliced isoform, DM20, are the major myelin proteins in the CNS, but are also expressed in the PNS. The proteins have an identical sequence except for 35 amino acids in PLP1 (the PLP1-specific domain) not present in DM20. Mutations of PLP1/DM20 cause Pelizaeus-Merzbacher Disease (PMD), a leukodystrophy, and in some instances, a peripheral neuropathy. To identify which mutations cause neuropathy, we have evaluated a cohort of patients with PMD and PLP1 mutations for the presence of neuropathy. As shown previously, all patients with PLP1 null mutations had peripheral neuropathy. We also identified 4 new PLP1 point mutations that cause both PMD and peripheral neuropathy, three of which truncate PLP1 expression within the PLP1-specific domain, but do not alter DM20. The fourth, a splicing mutation, alters both PLP1 and DM20, and is probably a null mutation. Six PLP1 point mutations predicted to produce proteins with an intact PLP1-specific domain do not cause peripheral neuropathy. Sixty-one individuals with PLP1 duplications also had normal peripheral nerve function. These data demonstrate that expression of PLP1 but not DMSO is necessary to prevent neuropathy, and suggest that the 35 amino acid PLP1-specific domain plays an important role in normal peripheral nerve function. PMID:12601703

  2. Gain-of-function Nav1.8 mutations in painful neuropathy.

    PubMed

    Faber, Catharina G; Lauria, Giuseppe; Merkies, Ingemar S J; Cheng, Xiaoyang; Han, Chongyang; Ahn, Hye-Sook; Persson, Anna-Karin; Hoeijmakers, Janneke G J; Gerrits, Monique M; Pierro, Tiziana; Lombardi, Raffaella; Kapetis, Dimos; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2012-11-20

    Painful peripheral neuropathy often occurs without apparent underlying cause. Gain-of-function variants of sodium channel Na(v)1.7 have recently been found in ∼30% of cases of idiopathic painful small-fiber neuropathy. Here, we describe mutations in Na(v)1.8, another sodium channel that is specifically expressed in dorsal root ganglion (DRG) neurons and peripheral nerve axons, in patients with painful neuropathy. Seven Na(v)1.8 mutations were identified in 9 subjects within a series of 104 patients with painful predominantly small-fiber neuropathy. Three mutations met criteria for potential pathogenicity based on predictive algorithms and were assessed by voltage and current clamp. Functional profiling showed that two of these three Na(v)1.8 mutations enhance the channel's response to depolarization and produce hyperexcitability in DRG neurons. These observations suggest that mutations of Na(v)1.8 contribute to painful peripheral neuropathy. PMID:23115331

  3. Contemporary medical management of peripheral arterial disease: a focus on risk reduction and symptom relief for intermittent claudication.

    PubMed

    Agrawal, Kush; Eberhardt, Robert T

    2015-02-01

    Peripheral arterial disease (PAD) is primarily caused by progressive systemic atherosclerosis manifesting in the lower extremities. This review addresses the epidemiology, clinical presentation and evaluation, and medical management of PAD, with a focus on intermittent claudication. Key advances in the recognition of cardiovascular risk in asymptomatic individuals with mildly abnormal ankle-brachial index, newer reflections on exercise therapy, and a review of established and investigational agents for the treatment of symptomatic PAD, such as cilostazol, statins, and angiotensin-converting enzyme inhibitors, are highlighted.

  4. 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.

  5. PMP22 related congenital hypomyelination neuropathy.

    PubMed

    Fabrizi, G M; Simonati, A; Taioli, F; Cavallaro, T; Ferrarini, M; Rigatelli, F; Pini, A; Mostacciuolo, M L; Rizzuto, N

    2001-01-01

    The peripheral myelin protein 22 (PMP22) is a tetraspan membrane protein which is localised in the compact myelin of the peripheral nerves. In fibroblasts, where it was originally identified as growth arrest related factor 3 (Gas3), PMP22 has been shown to modulate cell proliferation; in the peripheral nervous system its roles are still debated. The duplication of PMP22 is the most common cause of the demyelinating form of the autosomal dominant Charcot-Marie-Tooth neuropathy (CMT1A); rarer missense mutations of PMP22 also cause CMT1A or severe dehypomyelinating neuropathies of infancy grouped under the heading of Dejerine-Sottas syndrome (DSS). Here, a sporadic patient affected with DSS is described; nerve biopsy disclosed a picture of hypomyelination/amyelination with basal laminae onion bulbs and no florid demyelination and it was consistent with congenital hypomyelination neuropathy (CHN); molecular analysis disclosed a novel point mutation of PMP22 that causes a non-conservative arginine for cysteine substitution at codon 109, in the third transmembrane domain. CHN is the rarest and severest form of DSS and it is thought to reflect dysmyelination rather than demyelination. The reported case suggests that missense point mutations may alter a putative role of PMP22 in modulating Schwann cell growth and differentiation. PMID:11118262

  6. 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

  7. Necrotizing Lymphocytic Vasculitis Limited to the Peripheral Nerves: Report of Six Cases and Review

    PubMed Central

    Restrepo, José Félix; Rondón, Federico; Matteson, Eric L.; Colegial, Carlos H.; Quintana, Gerardo; Iglesias-Gamarra, Antonio

    2009-01-01

    Background. The systemic vasculitides are syndromes characterized by inflammation and injury (necrosis or thrombosis) of blood vessels, resulting in clinical manifestations according to the affected vascular bed, but not classically in stocking-glove neuropathy. Objective. To describe a form of primary vasculitis affecting strictly peripheral nerves manifesting as stocking-glove neuropathy. Methods. Case series of 110 patients seen in three centers in Bogotá who presented with symptoms and signs of polyneuropathy and/or were identified with vasculitis affecting only the peripheral nerves, and who underwent sural nerve biopsy. Results. Six patients had a vasculitis affecting only the peripheral nerves diagnosed on sural nerve biopsy which demonstrated a mixed infiltrate of monocytes/macrophages and lymphocytes especially in the small epineurial blood vessels. Over time, all had worsening of symptoms, with grip weakness and motor deficits in the hand and feet. Serologies and acute phase reactants were normal in all patients. Treatment response to immunosuppression was satisfactory in 5 patients; 1 patient had progressive neurologic damage. Conclusions. There is a distinct form of primary vasculitis of the peripheral nervous system characterized by distal sensory polyneuropathy with stocking-glove distribution with good prognosis, few and minor relapses and good response to treatment even after delayed diagnosis. PMID:20204175

  8. [Interconnection of the angiopathy and neuropathy development mechanism at patients with type II pancreatic diabetes].

    PubMed

    Saltykov, B B; Zinov'eva, O E

    2012-01-01

    In the article we summarized literature data, covered genesis of angiopathy and neuropathy at patients with type II diabetes. In the genesis of disease different metabolic, immune, hypoxic, genetic and others factors, caused affection of arteries, microcirculation and the peripheral nervous system, play an important role. Increasing changes of the great and minute vessels are interconnected with diabetic neuropathy

  9. Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy.

    PubMed

    Huang, Jianying; Han, Chongyang; Estacion, Mark; Vasylyev, Dymtro; Hoeijmakers, Janneke G J; Gerrits, Monique M; Tyrrell, Lynda; Lauria, Giuseppe; Faber, Catharina G; Dib-Hajj, Sulayman D; Merkies, Ingemar S J; Waxman, Stephen G

    2014-06-01

    Sodium channel Nav1.9 is expressed in peripheral nociceptive neurons, as well as visceral afferents, and has been shown to act as a threshold channel. Painful peripheral neuropathy represents a significant public health challenge and may involve gain-of-function variants in sodium channels that are preferentially expressed in peripheral sensory neurons. Although gain-of-function variants of peripheral sodium channels Nav1.7 and Nav1.8 have recently been found in painful small fibre neuropathy, the aetiology of peripheral neuropathy in many cases remains unknown. We evaluated 459 patients who were referred for possible painful peripheral neuropathy, and confirmed the diagnosis of small fibre neuropathy in a cohort of 393 patients (369 patients with pure small fibre neuropathy, and small fibre neuropathy together with large fibre involvement in an additional 24 patients). From this cohort of 393 patients with peripheral neuropathy, we sequenced SCN11A in 345 patients without mutations in SCN9A and SCN10A, and found eight variants in 12 patients. Functional profiling by electrophysiological recordings showed that these Nav1.9 mutations confer gain-of-function attributes to the channel, depolarize resting membrane potential of dorsal root ganglion neurons, enhance spontaneous firing, and increase evoked firing of these neurons. Our data show, for the first time, missense mutations of Nav1.9 in individuals with painful peripheral neuropathy. These genetic and functional observations identify missense mutations of Nav1.9 as a cause of painful peripheral neuropathy. PMID:24776970

  10. Traumatic optic neuropathy.

    PubMed

    Steinsapir, K D; Goldberg, R A

    1994-01-01

    Knowledge concerning the pathophysiologic mechanisms of traumatic optic neuropathy is limited. The optic nerve is a tract of the brain. Therefore, the cellular and biochemical pathophysiology of brain and spinal cord trauma and ischemia provide insight into mechanisms that may operate in traumatic optic neuropathy. The dosage of methylprednisolone (30 mg/kg/6 hours) which was successful in the National Acute Spinal Cord Injury Study 2 (NASCIS 2) evolved from the unique pharmacology of corticosteroids as antioxidants. The management of traumatic optic neuropathy rests on an accurate diagnosis which begins with a comprehensive clinical assessment and appropriate neuroimaging. The results of medical and surgical strategies for treating this injury have not been demonstrated to be better than those achieved without treatment. The spinal cord is a mixed grey and white matter tract of the brain in contrast to the optic nerve which is a pure white matter tract. The treatment success seen with methylprednisolone in the NASCIS 2 study may not generalize to the treatment of traumatic optic neuropathy. Conversely, if the treatment does generalize to the optic nerve, NASCIS 2 data suggests that treatment must be started within eight hours of injury, making traumatic optic neuropathy one of the true ophthalmic emergencies. Given the uncertainties in the treatment, ophthalmologists involved in the management of traumatic optic neuropathy are encouraged to participate in the collaborative study of traumatic optic neuropathy.

  11. 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

  12. 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.

  13. Wherefore Art Thou, O Treatment for Diabetic Neuropathy?

    PubMed

    Malik, R A

    2016-01-01

    As of March 2016, we continue to advocate the diagnosis of diabetic neuropathy using a simple foot examination or monofilament, which identifies only those with severe neuropathy and hence risk of foot ulceration. Given the fact that the 5-year mortality rate of diabetic patients with foot ulceration is worse than that of most common cancers, surely we should be identifying patients at an earlier stage of neuropathy to prevent its progression to a stage with such a high mortality? Of course, we lament that there is no licensed treatment for diabetic neuropathy. Who is to blame? As researchers and carers, we have a duty of care to our patients with diabetic neuropathy. So, we have to look forward not backwards, and move away from our firmly entrenched views on the design and conduct of clinical trials for diabetic neuropathy. Relevant organizations such as Neurodiab, the American Diabetes Association and the Peripheral Nerve Society have to acknowledge that they cannot continue to endorse a bankrupt strategy. The FDA needs an open and self-critical dialogue with these organizations, to give pharmaceutical companies at least a fighting chance to deliver effective new therapies for diabetic neuropathy.

  14. 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

  15. 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

  16. Progressive auditory neuropathy in patients with Leber's hereditary optic neuropathy

    PubMed Central

    Ceranic, B; Luxon, L

    2004-01-01

    Objective: To investigate auditory neural involvement in patients with Leber's hereditary optic neuropathy (LHON). Methods: Auditory assessment was undertaken in two patients with LHON. One was a 45 year old woman with Harding disease (multiple-sclerosis-like illness and positive 11778mtDNA mutation) and mild auditory symptoms, whose auditory function was monitored over five years. The other was a 59 year old man with positive 11778mtDNA mutation, who presented with a long standing progressive bilateral hearing loss, moderate on one side and severe to profound on the other. Standard pure tone audiometry, tympanometry, stapedial reflex threshold measurements, stapedial reflex decay, otoacoustic emissions with olivo-cochlear suppression, auditory brain stem responses, and vestibular function tests were undertaken. Results: Both patients had good cochlear function, as judged by otoacoustic emissions (intact outer hair cells) and normal stapedial reflexes (intact inner hair cells). A brain stem lesion was excluded by negative findings on imaging, recordable stapedial reflex thresholds, and, in one of the patients, olivocochlear suppression of otoacoustic emissions. The deterioration of auditory function implied a progressive course in both cases. Vestibular function was unaffected. Conclusions: The findings are consistent with auditory neuropathy—a lesion of the cochlear nerve presenting with abnormal auditory brain stem responses and with normal inner hair cells and the cochlear nucleus (lower brain stem). The association of auditory neuropathy, or any other auditory dysfunction, with LHON has not been recognised previously. Further studies are necessary to establish whether this is a consistent finding. PMID:15026512

  17. 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

  18. Diabetic neuropathy in children.

    PubMed

    Mah, Jean K; Pacaud, Danièle

    2014-01-01

    The worldwide burden of diabetes and its complications in children continues to increase due to the rise in type 1 and type 2 diabetes. Although overt diabetic neuropathy is rarely present in children and adolescents with diabetes, subclinical diabetic neuropathy has been estimated to occur in approximately half of all children with type 1 diabetes with a duration of 5 years or longer and up to 25% of pediatric patients with newly diagnosed diabetes have abnormal findings on nerve conduction studies. The present review on the state of pediatric diabetic neuropathy covers the definition, prevalence, pathogenesis, diagnosis, risk factors, and possible treatment approaches specific to children and adolescents with diabetes. It also highlights the many unknowns in this field. Nonetheless, new emerging interventions that can either prevent or delay the progression of diabetic microvascular and macrovascular complications may become available in the near future. Until specific interventions for diabetic neuropathy are available for use in children, it will be hard to justify screening for neuropathy other than through clinical assessment. Meanwhile, the search for quicker, easily administered, and quantifiable tests for diabetic neuropathy and efforts to establish valid pediatric norms for well-established measures used in adults will need to continue.

  19. 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

  20. Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome.

    PubMed

    Toschi-Dias, Edgar; Trombetta, Ivani C; da Silva, Valdo José Dias; Maki-Nunes, Cristiane; Alves, Maria Janieire N N; Angelo, Luciana F; Cepeda, Felipe X; Martinez, Daniel G; Negrão, Carlos Eduardo; Rondon, Maria Urbana P B

    2013-03-01

    Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.

  1. 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

  2. Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies.

    PubMed

    Gonzalez, Sergio; Berthelot, Jade; Jiner, Jennifer; Perrin-Tricaud, Claire; Fernando, Ruani; Chrast, Roman; Lenaers, Guy; Tricaud, Nicolas

    2016-03-01

    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

  3. 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

  4. Mouse Models of Diabetic Neuropathy

    PubMed Central

    O'Brien, Phillipe D.; Sakowski, Stacey A.; Feldman, Eva L.

    2014-01-01

    Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and is associated with significant morbidity and mortality. DPN is characterized by progressive, distal-to-proximal degeneration of peripheral nerves that leads to pain, weakness, and eventual loss of sensation. The mechanisms underlying DPN pathogenesis are uncertain, and other than tight glycemic control in type 1 patients, there is no effective treatment. Mouse models of type 1 (T1DM) and type 2 diabetes (T2DM) are critical to improving our understanding of DPN pathophysiology and developing novel treatment strategies. In this review, we discuss the most widely used T1DM and T2DM mouse models for DPN research, with emphasis on the main neurologic phenotype of each model. We also discuss important considerations for selecting appropriate models for T1DM and T2DM DPN studies and describe the promise of novel emerging diabetic mouse models for DPN research. The development, characterization, and comprehensive neurologic phenotyping of clinically relevant mouse models for T1DM and T2DM will provide valuable resources for future studies examining DPN pathogenesis and novel therapeutic strategies. PMID:24615439

  5. Peripherally Restricted Cannabinoids for the Treatment of Pain.

    PubMed

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

    2015-10-01

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

  6. [A case of Sotos syndrome associated with peripheral nerve involvements].

    PubMed

    Funakawa, I; Katoh, H; Hara, K; Yasuda, T; Terao, A

    1992-03-01

    A case of the Sotos syndrome associated with peripheral nerve involvements was reported. A 52-year-old male was admitted to Kawasaki Medical School Hospital because of gait disturbance, muscle atrophy, and weakness in both hands. This case was diagnosed as the Sotos syndrome based on the following symptoms and findings, acromegaloid features, hypertrophic changes in the hands and feet, a history of epileptic episodes, a low IQ, a normal growth hormone value, and no tumor lesion in the pituitary gland. Radiological examination disclosed a cauliflower-like appearance of the finger tips and thickness of the heel pads. Brain CT and MRI revealed diffuse mild brain atrophy. An electroencephalogram showed diffuse theta waves with sharp waves in the right parietal region. A needle electromyogram revealed neurogenic change in both upper and lower limbs. A nerve conduction study disclosed the carpal tunnel syndrome and cubital tunnel syndrome. These findings suggest that, as in the case of acromegaly, entrapment neuropathy and peripheral neuropathy can also be induced in the Sotos syndrome.

  7. [A case of Sotos syndrome associated with peripheral nerve involvements].

    PubMed

    Funakawa, I; Katoh, H; Hara, K; Yasuda, T; Terao, A

    1992-03-01

    A case of the Sotos syndrome associated with peripheral nerve involvements was reported. A 52-year-old male was admitted to Kawasaki Medical School Hospital because of gait disturbance, muscle atrophy, and weakness in both hands. This case was diagnosed as the Sotos syndrome based on the following symptoms and findings, acromegaloid features, hypertrophic changes in the hands and feet, a history of epileptic episodes, a low IQ, a normal growth hormone value, and no tumor lesion in the pituitary gland. Radiological examination disclosed a cauliflower-like appearance of the finger tips and thickness of the heel pads. Brain CT and MRI revealed diffuse mild brain atrophy. An electroencephalogram showed diffuse theta waves with sharp waves in the right parietal region. A needle electromyogram revealed neurogenic change in both upper and lower limbs. A nerve conduction study disclosed the carpal tunnel syndrome and cubital tunnel syndrome. These findings suggest that, as in the case of acromegaly, entrapment neuropathy and peripheral neuropathy can also be induced in the Sotos syndrome. PMID:1321017

  8. National Institute of Neurological Disorders and Stroke (NINDS): Advances in understanding and treating neuropathy, 24–25 October 2006; Bethesda, Maryland

    PubMed Central

    Feldman, Eva L.; Cornblath, David R.; Porter, John; Dworkin, Robert; Scherer, Steven

    2009-01-01

    National Institute of Neurological Disorders and Stroke sponsored a meeting to explore the current status of basic and clinical research in peripheral neurobiology and clinical neuropathy. The goal of the workshop was to identify areas where additional research could lead to the development of new therapeutics in the next 5 years. Participants discussed the current understanding of disease mechanisms of axonal and demyelinating neuropathies, existing techniques in research, disease biomarkers, and assessment of neuropathy. Painful neuropathies were discussed at the basic scientific and clinical levels in relation to new insights into etiology and treatment. The meeting concluded with a discussion on therapeutic development in neuropathy and the need for a unified approach to multicenter trials. Short-term goals of the workshop were to form a working group for neuropathy, the Peripheral Neuropathy Study Group, and to translate new scientific findings into therapies and complete clinical trials. PMID:18346227

  9. Ischemic optic neuropathy.

    PubMed

    Athappilly, Geetha; Pelak, Victoria S; Mandava, Naresh; Bennett, Jeffrey L

    2008-10-01

    Ischemic optic neuropathy is the most frequent cause of vision loss in middle age. Clinical and laboratory research studies have begun to clarify the natural history, clinical presentation, diagnostic criteria and pathogenesis of various ischemic nerve injuries. As a result, physicians are acquiring new tools to aid in the diagnosis and potential treatment of ischemic nerve injury. The aim of this review is to examine recent data on anterior and posterior ischemic optic neuropathy and to provide a framework for physicians to manage and counsel affected individuals. PMID:18826805

  10. Oral curcumin mitigates the clinical and neuropathologic phenotype of the Trembler-J mouse: a potential therapy for inherited neuropathy.

    PubMed

    Khajavi, Mehrdad; Shiga, Kensuke; Wiszniewski, Wojciech; He, Feng; Shaw, Chad A; Yan, Jiong; Wensel, Theodore G; Snipes, G Jackson; Lupski, James R

    2007-09-01

    Mutations in myelin genes cause inherited peripheral neuropathies that range in severity from adult-onset Charcot-Marie-Tooth disease type 1 to childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Many myelin gene mutants that cause severe disease, such as those in the myelin protein zero gene (MPZ) and the peripheral myelin protein 22 gene (PMP22), appear to make aberrant proteins that accumulate primarily within the endoplasmic reticulum (ER), resulting in Schwann cell death by apoptosis and, subsequently, peripheral neuropathy. We previously showed that curcumin supplementation could abrogate ER retention and aggregation-induced apoptosis associated with neuropathy-causing MPZ mutants. We now show reduced apoptosis after curcumin treatment of cells in tissue culture that express PMP22 mutants. Furthermore, we demonstrate that oral administration of curcumin partially mitigates the severe neuropathy phenotype of the Trembler-J mouse model in a dose-dependent manner. Administration of curcumin significantly decreases the percentage of apoptotic Schwann cells and results in increased number and size of myelinated axons in sciatic nerves, leading to improved motor performance. Our findings indicate that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and improves the neuropathologic phenotype in an animal model of human neuropathy, suggesting a potential therapeutic role in selected forms of inherited peripheral neuropathies. PMID:17701891

  11. 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

  12. 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.

  13. Ulnar Neuropathy After Extracorporeal Shockwave Therapy: A Case Report.

    PubMed

    Shim, Jae Seong; Chung, Sun G; Bang, Hyun; Lee, Hyuk Jin; Kim, Keewon

    2015-06-01

    Currently, extracorporeal shockwave therapy (ESWT) is widely used for treatment of various musculoskeletal disorders. We report a case of ulnar neuropathy secondary to the application of ESWT. A 48-year-old man was diagnosed with medial epicondylitis and underwent 2 sessions of ESWT. Immediately after the second session, he experienced paresthesia and weakness in the right hand. On physical examination, atrophy of the first dorsal interosseus and weakness of the abductor digiti minimi were observed. Electrophysiologic study demonstrated ulnar neuropathy at the elbow with severe partial axonotmesis. Our case report demonstrates that ESWT might cause or contribute to peripheral nerve injury at the site of application.

  14. Microvascular dysfunction in the context of diabetic neuropathy.

    PubMed

    Stirban, Alin

    2014-01-01

    Microvascular dysfunction in diabetes plays a crucial role in the development of diabetic complications. The skin, as one of the most accessible organs, serves as a model for the investigation of microvascular dysfunction. Several non-invasive, mostly laser-Doppler-based methods have been developed lately to assess microvascular function in the skin. Microvascular functional changes occur even in the prediabetic state and become more complex with overt diabetes, being exacerbated by the presence of peripheral and/or autonomic diabetic neuropathy. The present article aims at shedding light on the implication of endothelial and neurovascular dysfunction in microvascular changes in diabetes, highlighting the contribution of different forms of diabetic neuropathy.

  15. Suprascapular neuropathy in a collegiate pitcher.

    PubMed

    Smith, A N

    1995-03-01

    A healthy, 20-year-old, highly competitive collegiate baseball pitcher developed vague pain and soreness in the dominant posterior shoulder with live pitching. The symptoms intensified, and, after a particularly poor starting performance, the athlete presented for physical examination. Examination revealed visible atrophy of the infraspinatus muscle and decreased strength in external rotation and abduction. Magnetic Resonance Imaging was inconclusive. Electromyographic examination revealed decreased suprascapular nerve conduction to the infraspinatus muscle. Our diagnosis was entrapment neuropathy from traction on the suprascapular nerve at the spinoglenoid notch, causing delayed conduction to the infraspinatus muscle. We took a conservative approach of shoulder rehabilitation and activity modification, which resulted in the athlete returning to a highly competitive level without further problems, despite the remaining atrophy and muscle weakness. Examination of injuries to the shoulder complex, especially in athletes involved in repetitive overhead motions, should take suprascapular neuropathy into consideration.

  16. 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

  17. Recessive optic atrophy, sensorimotor neuropathy and cataract associated with novel compound heterozygous mutations in OPA1

    PubMed Central

    LEE, JINHO; JUNG, SUNG-CHUL; HONG, YOUNG BIN; YOO, JEONG HYUN; KOO, HEASOO; LEE, JA HYUN; HONG, HYUN DAE; KIM, SANG-BEOM; CHUNG, KI WHA; CHOI, BYUNG-OK

    2016-01-01

    Mutations in the optic atrophy 1 gene (OPA1) are associated with autosomal dominant optic atrophy and 20% of patients demonstrate extra-ocular manifestations. In addition to these autosomal dominant cases, only a few syndromic cases have been reported thus far with compound heterozygous OPA1 mutations, suggestive of either recessive or semi-dominant patterns of inheritance. The majority of these patients were diagnosed with Behr syndrome, characterized by optic atrophy, ataxia and peripheral neuropathy. The present study describes a 10-year-old boy with Behr syndrome presenting with early-onset severe optic atrophy, sensorimotor neuropathy, ataxia and congenital cataracts. He had optic atrophy and was declared legally blind at six years old. Electrophysiological, radiological, and histopathological findings were compatible with axonal sensorimotor polyneuropathy. At birth, he presented with a congenital cataract, which has not been previously described in patients with OPA1 mutations. Whole exome sequencing indicated a pair of novel compound heterozygous mutations: p.L620fs*13 (c.1857–1858delinsT) and p.R905Q (c.G2714A). Neither mutation was observed in controls (n=300), and thus, they were predicted to be pathogenic by multiple in silico analyses. The mutation sites were highly conserved throughout different vertebrate species. The patients parents did not have any ophthalmic or neurologic symptoms and the results of electrophysiological studies were normal, suggestive of an autosomal recessive pattern of inheritance. The present study identified novel compound heterozygous OPA1 mutations in a patient with recessive optic atrophy, sensorimotor neuropathy and congenital cataracts, indicating an expansion of the clinical spectrum of pathologies associated with OPA1 mutations. Thus, OPA1 gene screening is advisable in the workup of patients with recessive optic atrophy, particularly with Behr syndrome and cataracts. PMID:27150940

  18. Neuroactive steroids and the peripheral nervous system: An update.

    PubMed

    Giatti, Silvia; Romano, Simone; Pesaresi, Marzia; Cermenati, Gaia; Mitro, Nico; Caruso, Donatella; Tetel, Marc J; Garcia-Segura, Luis Miguel; Melcangi, Roberto C

    2015-11-01

    In the present review we summarize observations to date supporting the concept that neuroactive steroids are synthesized in the peripheral nervous system, regulate the physiology of peripheral nerves and exert notable neuroprotective actions. Indeed, neuroactive steroids have been recently proposed as therapies for different types of peripheral neuropathy, like for instance those occurring during aging, chemotherapy, physical injury and diabetes. Moreover, pharmacological tools able to increase the synthesis of neuroactive steroids might represent new interesting therapeutic strategy to be applied in case of peripheral neuropathy.

  19. Neurotoxicity of acrylamide and its analogues and effects of these analogues and other agents on acrylamide neuropathy.

    PubMed Central

    Edwards, P M

    1975-01-01

    N-Hydroxymethylacrylamide, N-methylacrylamide, and N,N-diethylacrylamide produce peripheral neuropathy in rats. Seven other compounds related to acrylamide do not produce neuropathy. Rats given one of the three neurotoxic compounds are more susceptible to acrylamide. A regime for testing acrylamide analogues for neuro-toxicity is suggested. DDT, phenobarbitone, or high dietary concentrations of vitamin A or E have no effect on the development of acrylamide neuropathy in rats. Acrylamide produces neuropathy in hens but not in frogs or goldfish. PMID:164879

  20. The clinical spectrum of amiodarone-associated optic neuropathy.

    PubMed Central

    Johnson, Lenworth N.; Krohel, Gregory B.; Thomas, Eric R.

    2004-01-01

    PURPOSE: To describe the clinical spectrum of amiodarone-associated optic neuropathy. METHODS: Observational cases series and review. RESULTS: Of 55 cases, the median interval for onset of optic neuropathy was four months after initiating amiodarone; 88% occurred within 12 months. Seven (13%) patients were asymptomatic. Twenty-two (40%) patients presented with sudden visual loss, while 26 (47%) had insidious loss of vision. Visual acuity ranged from 20/15 to light perception; 10 (18%) patients had legal blindness with visual acuity of 20/200 or worse. Visual field loss was present in 91% of cases. Color vision loss was present in eight (40%) of 20 cases. Optic disc edema was present in 85% of cases, while eight (15%) patients had retrobulbar optic neuropathy, without evidence of disc edema. Optic disc edema resolved over a median time of three months. Five patients had raised intracranial pressure on lumbar puncture. CONCLUSION: We were able to classify amiodarone-associated optic neuropathy into five clinical categories with respect to temporal characteristics and optic nerve appearance: insidious-onset (43%), acute-onset (28%), retrobulbar (13%), increased intracranial pressure (8%), and delayed-progressive onset (8%). Most cases of optic neuropathy commenced within 12 months of initiating amiodarone, with the median onset being four months. Over 10% of patients will have no visual symptoms at the onset. Ophthalmologic examinations within the first 12 months--and particularly within four months of initiating amiodarone--should improve early detection of amiodarone-associated optic neuropathy. PMID:15586652

  1. Sjögren Syndrome-Associated Small Fiber Neuropathy: Characterization From a Prospective Series of 40 Cases.

    PubMed

    Sène, Damien; Cacoub, Patrice; Authier, François-Jérôme; Haroche, Julien; Créange, Alain; Saadoun, David; Amoura, Zahir; Guillausseau, Pierre-Jean; Lefaucheur, Jean-Pascal

    2013-08-26

    We conducted the current study to analyze the clinical, immunologic, and neurophysiologic features of primary Sjögren syndrome (pSS)-associated sensory small fiber neuropathies (SFNs). Forty consecutive pSS patients with SFN were included. SFN was defined by the presence of suggestive sensory painful symptoms with normal nerve conduction studies and abnormal neurophysiologic tests for small nerve fibers or a low intraepidermal nerve fiber density at skin biopsy. Included patients were compared to 100 pSS patients without peripheral neuropathy.SFN patients were mainly female (92.5%). Age at pSS diagnosis was 55.3 ± 13.1 years, and at SFN diagnosis, 58.9 ± 11.8 years, with a median time to SFN diagnosis after symptom onset of 3.4 years. Clinical symptoms included burning pains (90%), numbness (87.5%), tingling (82.5%), pins and needles (72.5%), electric discharges (70%), and allodynia (55%). Dysautonomia included vasomotor symptoms (66%) and hyperhidrosis (47%). Abnormal neurophysiologic tests included laser evoked potentials (97.5%), thermal quantitative sensory testing (67.5%), and sympathetic skin reflex (40%). A skin biopsy revealed low intraepidermal nerve fiber density in 76% of the 17 tested patients.Compared to the 100 pSS patients without peripheral neuropathy, the 40 pSS-SFN patients were older at pSS diagnosis (55.3 ± 13.1 vs. 49.5 ± 14.9 yr; p = 0.03), and more often had xerostomia (97.5% vs. 81%; p = 0.01) and arthralgia (82.5% vs. 65.0%; p = 0.04). Immunologically, they were characterized by a lower prevalence of serum B-cell activation markers, that is, antinuclear antibodies (65% vs. 85%; p = 0.01), anti-SSA (42.5% vs. 71%; p = 0.002), and anti-SSB (17.5% vs. 39%; p = 0.017); rheumatoid factor (32.5% vs. 66%; p = 0.0005); and hypergammaglobulinemia (35% vs. 62%; p = 0.005).In conclusion, we report the main features of SFN in patients with pSS, the first such study to our knowledge. Our results show that patients with pSS-associated SFN are

  2. Genetics Home Reference: Leber hereditary optic neuropathy

    MedlinePlus

    ... Conditions Leber hereditary optic neuropathy Leber hereditary optic neuropathy Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Leber hereditary optic neuropathy (LHON) is an inherited form of vision loss. ...

  3. Genetics Home Reference: ataxia neuropathy spectrum

    MedlinePlus

    ... Genetics Home Health Conditions ataxia neuropathy spectrum ataxia neuropathy spectrum Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Ataxia neuropathy spectrum is part of a group of conditions ...

  4. Genetics Home Reference: small fiber neuropathy

    MedlinePlus

    ... Home Health Conditions small fiber neuropathy small fiber neuropathy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Small fiber neuropathy is a condition characterized by severe pain attacks ...

  5. Relationship of axonal voltage-gated sodium channel 1.8 (NaV1.8) mRNA accumulation to sciatic nerve injury-induced painful neuropathy in rats.

    PubMed

    Ruangsri, Supanigar; Lin, Audrey; Mulpuri, Yatendra; Lee, Kyung; Spigelman, Igor; Nishimura, Ichiro

    2011-11-18

    Painful peripheral neuropathy is a significant clinical problem; however, its pathological mechanism and effective treatments remain elusive. Increased peripheral expression of tetrodotoxin-resistant voltage-gated sodium channel 1.8 (NaV1.8) has been shown to associate with chronic pain symptoms in humans and experimental animals. Sciatic nerve entrapment (SNE) injury was used to develop neuropathic pain symptoms in rats, resulting in increased NaV1.8 mRNA in the injured nerve but not in dorsal root ganglia (DRG). To study the role of NaV1.8 mRNA in the pathogenesis of SNE-induced painful neuropathy, NaV1.8 shRNA vector was delivered by subcutaneous injection of cationized gelatin/plasmid DNA polyplex into the rat hindpaw and its subsequent retrograde transport via sciatic nerve to DRG. This in vivo NaV1.8 shRNA treatment reversibly and repeatedly attenuated the SNE-induced pain symptoms, an effect that became apparent following a distinct lag period of 3-4 days and lasted for 4-6 days before returning to pretreatment levels. Surprisingly, apparent knockdown of NaV1.8 mRNA occurred only in the injured nerve, not in the DRG, during the pain alleviation period. Levels of heteronuclear NaV1.8 RNA were unaffected by SNE or shRNA treatments, suggesting that transcription of the Scn10a gene encoding NaV1.8 was unchanged. Based on these data, we postulate that increased axonal mRNA transport results in accumulation of functional NaV1.8 protein in the injured nerve and the development of painful neuropathy symptoms. Thus, targeted delivery of agents that interfere with axonal NaV1.8 mRNA may represent effective neuropathic pain treatments. PMID:21965668

  6. [Leber's hereditary optic neuropathy].

    PubMed

    Hilo, Wasseem; Jabaly-Habib, Haneen; Modi, Naftali; Briscoe, Daniel

    2013-08-01

    Lebers hereditary optic neuropathy (LHON) is a maternally inherited disease characterized by subacute severe visual loss in both eyes, which usually manifests in young adulthood. The disease has maternal inheritance due to mitochondrial DNA mutation. The final diagnosis is genetic. There is still no proven treatment, but there is significant progress in developments on the genetics of the disease to reach gene therapy. In this article we review the latest literature relevant to this disease.

  7. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice.

    PubMed

    Trammell, Samuel A J; Weidemann, Benjamin J; Chadda, Ankita; Yorek, Matthew S; Holmes, Amey; Coppey, Lawrence J; Obrosov, Alexander; Kardon, Randy H; Yorek, Mark A; Brenner, Charles

    2016-01-01

    Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP(+) and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies. PMID:27230286

  8. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice

    PubMed Central

    Trammell, Samuel A.J.; Weidemann, Benjamin J.; Chadda, Ankita; Yorek, Matthew S.; Holmes, Amey; Coppey, Lawrence J.; Obrosov, Alexander; Kardon, Randy H.; Yorek, Mark A.; Brenner, Charles

    2016-01-01

    Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD+ metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP+ and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies. PMID:27230286

  9. Hereditary Neuropathy with Liability to Pressure Palsy Presenting as an Acute Brachial Plexopathy: A Lover's Palsy

    PubMed Central

    Wedderburn, Sarah; Pateria, Puraskar; Panegyres, Peter K.

    2014-01-01

    It is generally regarded that patients with hereditary neuropathy to pressure palsies, due to a deletion in the PMP22 gene, show recurrent pressure palsy and generalised peripheral neuropathy (pes cavus and hammer toes sometimes develop). Brachial plexopathy is rarely identified as a first presentation of hereditary neuropathy to pressure palsies. We describe a young man who developed a painless flail upper limb with a clinical diagnosis of a brachial plexopathy after his partner slept on his arm – a PMP22 deletion was found. His father, who had a symmetrical polyneuropathy without recurrent mononeuropathies, shared the PMP22 deletion. PMID:25685136

  10. Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency

    PubMed Central

    Yaghini, Omid

    2016-01-01

    Biotinidase deficiency is a disorder inherited autosomal recessively showing evidence of hearing loss and optic atrophy in addition to seizures, hypotonia, and ataxia. In the present study, a 2-year-old boy with Biotinidase deficiency is presented in which clinical symptoms have been reported with auditory neuropathy/auditory dyssynchrony (AN/AD). In this case, transient-evoked otoacoustic emissions showed bilaterally normal responses representing normal function of outer hair cells. In contrast, acoustic reflex test showed absent reflexes bilaterally, and visual reinforcement audiometry and auditory brainstem responses indicated severe to profound hearing loss in both ears. These results suggest AN/AD in patients with Biotinidase deficiency. PMID:27144235

  11. Mesenchymal stem cells to treat diabetic neuropathy: a long and strenuous way from bench to the clinic.

    PubMed

    Zhou, J Y; Zhang, Z; Qian, G S

    2016-01-01

    As one of the most common complications of diabetes, diabetic neuropathy often causes foot ulcers and even limb amputations. Inspite of continuous development in antidiabetic drugs, there is still no efficient therapy to cure diabetic neuropathy. Diabetic neuropathy shows declined vascularity in peripheral nerves and lack of angiogenic and neurotrophic factors. Mesenchymal stem cells (MSCs) have been indicated as a novel emerging regenerative therapy for diabetic neuropathy because of their multipotency. We will briefly review the pathogenesis of diabetic neuropathy, characteristic of MSCs, effects of MSC therapies for diabetic neuropathy and its related mechanisms. In order to treat diabetic neuropathy, neurotrophic or angiogenic factors in the form of protein or gene therapy are delivered to diabetic neuropathy, but therapeutic efficiencies are very modest if not ineffective. MSC treatment reverses manifestations of diabetic neuropathy. MSCs have an important role to repair tissue and to lower blood glucose level. MSCs even paracrinely secrete neurotrophic factors, angiogenic factors, cytokines, and immunomodulatory substances to ameliorate diabetic neuropathy. There are still several challenges in the clinical translation of MSC therapy, such as safety, optimal dose of administration, optimal mode of cell delivery, issues of MSC heterogeneity, clinically meaningful engraftment, autologous or allogeneic approach, challenges with cell manufacture, and further mechanisms.

  12. Mesenchymal stem cells to treat diabetic neuropathy: a long and strenuous way from bench to the clinic

    PubMed Central

    Zhou, J Y; Zhang, Z; Qian, G S

    2016-01-01

    As one of the most common complications of diabetes, diabetic neuropathy often causes foot ulcers and even limb amputations. Inspite of continuous development in antidiabetic drugs, there is still no efficient therapy to cure diabetic neuropathy. Diabetic neuropathy shows declined vascularity in peripheral nerves and lack of angiogenic and neurotrophic factors. Mesenchymal stem cells (MSCs) have been indicated as a novel emerging regenerative therapy for diabetic neuropathy because of their multipotency. We will briefly review the pathogenesis of diabetic neuropathy, characteristic of MSCs, effects of MSC therapies for diabetic neuropathy and its related mechanisms. In order to treat diabetic neuropathy, neurotrophic or angiogenic factors in the form of protein or gene therapy are delivered to diabetic neuropathy, but therapeutic efficiencies are very modest if not ineffective. MSC treatment reverses manifestations of diabetic neuropathy. MSCs have an important role to repair tissue and to lower blood glucose level. MSCs even paracrinely secrete neurotrophic factors, angiogenic factors, cytokines, and immunomodulatory substances to ameliorate diabetic neuropathy. There are still several challenges in the clinical translation of MSC therapy, such as safety, optimal dose of administration, optimal mode of cell delivery, issues of MSC heterogeneity, clinically meaningful engraftment, autologous or allogeneic approach, challenges with cell manufacture, and further mechanisms. PMID:27551543

  13. Mesenchymal stem cells to treat diabetic neuropathy: a long and strenuous way from bench to the clinic.

    PubMed

    Zhou, J Y; Zhang, Z; Qian, G S

    2016-01-01

    As one of the most common complications of diabetes, diabetic neuropathy often causes foot ulcers and even limb amputations. Inspite of continuous development in antidiabetic drugs, there is still no efficient therapy to cure diabetic neuropathy. Diabetic neuropathy shows declined vascularity in peripheral nerves and lack of angiogenic and neurotrophic factors. Mesenchymal stem cells (MSCs) have been indicated as a novel emerging regenerative therapy for diabetic neuropathy because of their multipotency. We will briefly review the pathogenesis of diabetic neuropathy, characteristic of MSCs, effects of MSC therapies for diabetic neuropathy and its related mechanisms. In order to treat diabetic neuropathy, neurotrophic or angiogenic factors in the form of protein or gene therapy are delivered to diabetic neuropathy, but therapeutic efficiencies are very modest if not ineffective. MSC treatment reverses manifestations of diabetic neuropathy. MSCs have an important role to repair tissue and to lower blood glucose level. MSCs even paracrinely secrete neurotrophic factors, angiogenic factors, cytokines, and immunomodulatory substances to ameliorate diabetic neuropathy. There are still several challenges in the clinical translation of MSC therapy, such as safety, optimal dose of administration, optimal mode of cell delivery, issues of MSC heterogeneity, clinically meaningful engraftment, autologous or allogeneic approach, challenges with cell manufacture, and further mechanisms. PMID:27551543

  14. Phenotyping animal models of diabetic neuropathy: a consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab).

    PubMed

    Biessels, G J; Bril, V; Calcutt, N A; Cameron, N E; Cotter, M A; Dobrowsky, R; Feldman, E L; Fernyhough, P; Jakobsen, J; Malik, R A; Mizisin, A P; Oates, P J; Obrosova, I G; Pop-Busui, R; Russell, J W; Sima, A A; Stevens, M J; Schmidt, R E; Tesfaye, S; Veves, A; Vinik, A I; Wright, D E; Yagihashi, S; Yorek, M A; Ziegler, D; Zochodne, D W

    2014-06-01

    NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current understanding of each area, gold standards (if applicable) for assessments of function, improvements of existing techniques, and utility of known and exploratory biomarkers. The research opportunities in each area were outlined, providing a possible roadmap for future studies. The meeting concluded with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted toward the therapeutic efficacy of drug interventions.

  15. Nerve Growth Factor and Diabetic Neuropathy

    PubMed Central

    Vinik, Aaron

    2003-01-01

    Neuropathy is one of the most debilitating complications of both type 1 and type 2 diabetes, with estimates of prevalence between 50–90% depending on the means of detection. Diabetic neuropathies are heterogeneous and there is variable involvement of large myelinated fibers and small, thinly myelinated fibers. Many of the neuronal abnormalities in diabetes can be duplicated by experimental depletion of specific neurotrophic factors, their receptors or their binding proteins. In experimental models of diabetes there is a reduction in the availability of these growth factors, which may be a consequence of metabolic abnormalities, or may be independent of glycemic control. These neurotrophic factors are required for the maintenance of the neurons, the ability to resist apoptosis and regenerative capacity. The best studied of the neurotrophic factors is nerve growth factor (NGF) and the related members of the neurotrophin family of peptides. There is increasing evidence that there is a deficiency of NGF in diabetes, as well as the dependent neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) that may also contribute to the clinical symptoms resulting from small fiber dysfunction. Similarly, NT3 appears to be important for large fiber and IGFs for autonomic neuropathy. Whether the observed growth factor deficiencies are due to decreased synthesis, or functional, e.g. an inability to bind to their receptor, and/or abnormalities in nerve transport and processing, remains to be established. Although early studies in humans on the role of neurotrophic factors as a therapy for diabetic neuropathy have been unsuccessful, newer agents and the possibilities uncovered by further studies should fuel clinical trials for several generations. It seems reasonable to anticipate that neurotrophic factor therapy, specifically targeted at different nerve fiber populations, might enter the therapeutic armamentarium. PMID:14668049

  16. Neurophysiological approach to disorders of peripheral nerve.

    PubMed

    Crone, Clarissa; Krarup, Christian

    2013-01-01

    Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves, plexus, or root lesions). Furthermore pathological processes may result in either demyelination, axonal degeneration or both. In order to reach an exact diagnosis of any neuropathy electrophysiological studies are crucial to obtain information about these variables. Conventional electrophysiological methods including nerve conduction studies and electromyography used in the study of patients suspected of having a neuropathy and the significance of the findings are discussed in detail and more novel and experimental methods are mentioned. Diagnostic considerations are based on a flow chart classifying neuropathies into eight categories based on mode of onset, distribution, and electrophysiological findings, and the electrophysiological characteristics in each type of neuropathy are discussed. PMID:23931776

  17. Diagnostic pitfalls: posterior ischemic optic neuropathy mimicking optic neuritis.

    PubMed

    Lysandropoulos, Andreas P; Carota, Antonio

    2011-02-01

    In young people, the most frequent cause of isolated monocular visual loss due to an optic neuropathy is optic neuritis. We present the case of a 27 year old woman who presented monocular visual loss, excruciating orbital pain and unusual temporal headache. The initial diagnosis of optic neuritis revealed later to be a posterior ischemic optic neuropathy (PION). In this case, PION was the first unique presentation of a non-traumatic carotid dissection, and it was followed 24h later by an ischemic stroke. Sudden monocular visual loss associated with a new-onset headache are clinical symptoms that should immediately prompt to a carotid dissection. PMID:21056537

  18. Autonomic Involvement in Subacute and Chronic Immune-Mediated Neuropathies

    PubMed Central

    Mazzeo, Anna; Stancanelli, Claudia; Vita, Giuseppe

    2013-01-01

    Autonomic function can be impaired in many disorders in which sympathetic, parasympathetic, and enteric arms of the autonomic nervous system are affected. Signs and symptoms of autonomic involvement are related to impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic functions. Availability of noninvasive, sensitive, and reproducible tests can help to recognize these disorders and to better understand specific mechanisms of some, potentially treatable, immune-mediated autonomic neuropathies. This paper describes autonomic involvement in immune-mediated neuropathies with a subacute or chronic course. PMID:23853716

  19. Giant axonal neuropathy: a rare inherited neuropathy with simple clinical clues

    PubMed Central

    Kamate, Mahesh; Ramakrishna, Shashikala; Ka