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Sample records for sciatic neuropathy

  1. Hereditary neuropathy with liability to pressure palsies presenting with sciatic neuropathy.

    PubMed

    Topakian, Raffi; Wimmer, Sibylle; Pischinger, Barbara; Pichler, Robert

    2014-10-17

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder associated with recurrent mononeuropathies following compression or trivial trauma. Reports on sciatic neuropathy as the presenting manifestation of HNPP are very scarce. We report on a 21-year-old previously healthy man who was admitted with sensorimotor deficits in his left leg. He had no history of preceding transient episodes of weakness or sensory loss. Clinical and electrophysiological examinations were consistent with sciatic neuropathy. Cerebrospinal fluid investigation and MRI of the nerve roots, plexus, and sciatic nerve did not indicate the underlying aetiology. When extended electrophysiological tests revealed multiple subclinical compression neuropathies in the upper limbs, HNPP was contemplated and eventually confirmed by genetic testing.

  2. [A case of localized hypertrophic neuropathy in the sciatic nerve].

    PubMed

    Izumi, T; Kusaka, H; Imai, T

    1995-01-01

    A 26-year-old male patient gradually developed muscular atrophy of the right lower leg over a two-year period. Neurological examination revealed absent Achilles tendon reflex and muscular atrophy of the right lower leg and right hamstring muscles. Conduction velocity of the F waves was delayed in the right posterior tibial nerve. A computerized tomography scan and magnetic resonance imaging revealed a mass lesion along the proximal segment of the right sciatic nerve. Exploration revealed a fusiformly swollen sciatic nerve. Histological examination showed that a swollen segment of the sciatic nerve was filled with onion-bulb formations of perineurial cells, consistent with the diagnosis of localized hypertrophic neuropathy. This condition should be added to several etiologies of monomelic amyotrophy. Electrophysiological studies and neuroimaging techniques were useful in obtaining differential diagnosis.

  3. Severe isolated sciatic neuropathy due to a modified lotus position

    PubMed Central

    Bosma, Jacob Wycher; Wijntjes, Juerd; Hilgevoord, Ton Antonius; Veenstra, Jan

    2014-01-01

    A 51-year-old man presented to our hospital with progressive pain and weakness in his right leg. Neurological examination revealed atrophy of all muscles of the right leg, unilateral foot drop and paralysis of the anterior tibial and gastrocnemicus muscles. Electromyography confirmed a severe isolated sciatic neuropathy in the thigh. For unclear reasons, our patient habitually used to sit in a modified lotus position. We concluded that this position, in literature known as “lotus neuropathy” had resulted in the sciatic neuropathy. After more than a year our patient was referred again to our outpatient clinic. At that time there was only minimal improvement, now with an achilles tendon contracture and pes equinus due to immobility. PMID:24579070

  4. Sciatic neuropathies--a retrospective review of electrodiagnostic features in 29 patients.

    PubMed

    Goh, K J; Tan, C B; Tjia, H T

    1996-07-01

    Sciatic neuropathy is an uncommonly diagnosed focal mononeuropathy. We reviewed the aetiology and electrodiagnostic features of 29 patients studied at the Neurodiagnostic Laboratory, Tan Tock Seng Hospital from January 1989 to April 1995. External nerve compression was the most common cause (38%) followed by trauma (21%). Other rare causes in this series included intragluteal injections, hip surgery and diabetic mononeuropathy while 24% had uncertain aetiology. Electrodiagnostic studies showed preferential involvement of the peroneal division in 51%. Axonal loss was found in 97%. We conclude that sciatic neuropathy often mimics distal peroneal nerve dysfunction and neurophysiological studies are essential for diagnosis. Furthermore, these studies are necessary for assessing prognosis in relation to axonal loss.

  5. Study on the use of quantitative ultrasound evaluation of diabetic neuropathy in the rat sciatic nerve.

    PubMed

    Huang, Yunxia; Hu, Bing; Zhu, Jiaan

    2016-12-01

    Ultrasound is an effective tool for peripheral disease with direct imaging of morphological and echogenic changes, but it has limitations when applied to evaluation of diabetic peripheral neuropathy. The aim of this study was to assess the role of ultrasound to quantitatively evaluate diabetic peripheral neuropathy in rat sciatic nerve. In our experiments, ultrasound imaging and electrophysiological examination testing of sciatic nerves were monitored in diabetic and control rats at the period of 1st and 4th month of hyperglycemia. Cross sectional area, intraneural echo intensity, inner diameter, motor nerve conduction velocity, and histological changes were measured and compared between diabetic and control groups. Intraneural hyperechoic were observed in the diabetic rats, and the echo intensity of the sciatic nerve was increased in diabetic rats rather than control lean rats at 4th month of hyperglycemia (p < 0.05), which has shown a similar correlation with functional deficit and histological changes based on the severity of diabetic peripheral neuropathy. We conclude that the echo intensity is potentially useful in detecting diabetic peripheral neuropathy, which can pave the way for more accurate and efficient diagnosis in clinical study.

  6. Bilateral Sciatic Neuropathy after an Autologous Breast Reconstruction in a Massive Weight Loss Patient

    PubMed Central

    Ablavsky, Michael; Shteynberg, Aleksandr

    2017-01-01

    Summary: Perioperative compression neuropathy is a known potential complication of prolonged surgical procedures. Sciatic postoperative neuropathy has rarely been reported. We present a 34-year-old woman who underwent right breast reconstruction with supercharged (venous anastomosis) transverse rectus abdominis flap and developed bilateral sciatic compression neuropathy. Her history was remarkable for sleeve gastrectomy 2 years earlier resulting in 105 pound weight loss 1 year before breast reconstruction. During the procedure, the patient was in the supine position for 8 hours and in the semirecumbent position for an additional 2 hours with the torso flexed at 30 degrees and knees flexed at approximately 45 degrees in addition to standard padding. Postoperatively, the patient was found to have loss of sensation and motor paralysis distal to her knees bilaterally. Pain sensation was preserved distally and no other neurological abnormalities were noted. Laboratory tests, magnetic resonance imaging, electromyography, and nerve conduction studies all revealed no evidence of neurological lesions and peroneal or lumbosacral radiculopathy. Motor strength gradually returned to her lower extremities over 4–5 weeks, whereas sensory function continued to improve over 7 weeks. The patient had complete neurological recovery 2 months postoperatively. PMID:28203505

  7. 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

  8. 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.

  9. Gene expression microarray analysis of the sciatic nerve of mice with diabetic neuropathy

    PubMed Central

    ZHANG, LEI; QU, SHEN; LIANG, AIBIN; JIANG, HONG; WANG, HAO

    2015-01-01

    The present study aimed to explore novel target genes that regulate the development of diabetic neuropathy (DN) by analyzing gene expression profiles in the sciatic nerve of infected mice. The GSE11343 microarray dataset, which was downloaded from Gene Expression Omnibus, included data on 4 control samples and 5 samples from mice with diabetes induced by streptozotocin (STZ), 5 samples from normal mice treated with rosiglitazone (Rosi) and 5 samples from mice with diabetes induced by STZ and treated with Rosi. Differentially expressed genes (DEGs) between the different groups were identified using the substitution augmentation modification redefinition (SAMR) model. The Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Regulatory and protein-protein interaction networks were searched using BioCarta and STRING, respectively. The protein structures of potential regulatory genes were predicted using the SYBYL program. Compared with the controls, 1,384 DEGs were identified in the mice with STZ-induced diabetes and 7 DEGs were identified in the mice treated with Rosi. There were 518 DEGs identified between the mice in the STZ + Rosi and STZ groups. We identified 45 GO items, and the calmodulin nerve phosphatase and chemokine signaling pathways were identified as the main pathways. Three genes [myristoylated alanine-rich protein kinase C substrate (Marcks), GLI pathogenesis-related 2 (Glipr2) and centrosomal protein 170 kDa (Cep170)] were found to be co-regulated by both STZ and Rosi, the protein structure of which was predicted and certain binding activity to Rosi was docked. Our study demonstrates that the Marcks, Glipr2 and Cep170 genes may be underlying drug targets in the treatment of DN. PMID:25435094

  10. Preventive Effects of the Chinese Herbal Medicine Prescription Tangkuei Decoction for Frigid Extremities on Sciatic Neuropathy in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Liu, Pengsong; Bian, Yuanyuan; Zhang, Hong; Jia, Aiming

    2016-01-01

    Ischemia and hypoxia are important physiological changes in diabetic peripheral neuropathy (DPN). Chinese herbal medicine prescription Tangkuei Decoction for Frigid Extremities (TDFE) is useful for increasing blood flow. To help determine whether TDFE could protect the peripheral nerves of diabetic patients from the degeneration caused by high blood glucose, TDFE was administered to streptozotocin-induced diabetic rats for 6 or 12 weeks. Plantar thermal stimulation reaction time thresholds, sciatic nerve conduction velocities, and the levels of HIF-1α mRNA, HIF-1α protein, VEGF protein, and the endothelial marker vWF in sciatic nerves were measured at the end of the sixth and twelfth weeks. The thermal thresholds and sciatic nerve conduction velocities of the rats differed after 12 weeks, and the sciatic nerves of the diabetic rats that were given TDFE displayed higher levels of HIF-1α protein, VEGF protein, and HIF-1α mRNA than those of the diabetic model rats. The results at 6 weeks differed from those at 12 weeks. These results suggest that the early preventive application of TDFE effectively delayed the development of DPN and that TDFE increased HIF-1α mRNA levels in the sciatic nerves of diabetic rats through 12 weeks of treatment. PMID:27057201

  11. 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.

  12. Localization and expression of ciliary neurotrophic factor (CNTF) in postmortem sciatic nerve from patients with motor neuron disease and diabetic neuropathy

    SciTech Connect

    Lee, D.A.; Gross, L.; Wittrock, D.A.; Windebank, A.J.

    1996-08-01

    Ciliary neurotrophic factor (CNTF) is thought to play an important role in the maintenance of the mature motor system. The factor is found most abundantly in myelinating Schwann cells in the adult sciatic nerve. Lack of neuronal growth factors has been proposed as one possible etiology of amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Growth factor replacement therapies are currently being evaluated as a treatment for motor neuron disease. In this report we determined whether the expression of CNTF in sciatic nerve differed in patients with motor neuron disease compared to controls or patients with another form of axonopathy. We identified 8 patients (7 with ALS and 1 with SMA) with motor neuron disease and 6 patients with diabetic motor neuropathy who had autopsy material available. Immunoperoxidase staining showed reduced CNTF expression in nerves of patients with motor neuron disease but not in patients with diabetic motor neuropathy. Decreased CNTF appears be associated with primary motor neuron disease rather than a generalized process of axon loss. This result supports suggestions that CNTF deficiency may be an important factor in the development of motor neuron disease. 20 refs., 4 figs., 1 tab.

  13. Deep venous thrombosis and inferior vena cava agenesis causing double crush sciatic neuropathy in Behçet's disease.

    PubMed

    Kara, Murat; Ozçakar, Levent; Eken, Güneş; Ozen, Gülsen; Kiraz, Sedat

    2008-12-01

    We report here the case of a 18-year-old young man with Behçet's disease who had suffered deep venous thrombosis of the right femoral and popliteal veins. Consequently, right sciatic nerve injury, drop foot and tightness of the achilles tendon also ensued. The clinical scenario was further challenged by demonstration of the agenetic inferior vena cava and epidural vein dilatations compressing the lumbar nerve roots. To the best notice of the authors, this is the first patient encompassing all these complications in the literature concerning Behçet's disease.

  14. Piriformis syndrome surgery causing severe sciatic nerve injury.

    PubMed

    Justice, Phillip E; Katirji, Bashar; Preston, David C; Grossman, Gerald E

    2012-09-01

    Piriformis syndrome is a controversial entrapment neuropathy in which the sciatic nerve is thought to be compressed by the piriformis muscle. Two patients developed severe left sciatic neuropathy after piriformis muscle release. One had a total sciatic nerve lesion, whereas the second had a predominantly high common peroneal nerve lesion. Follow-up studies showed reinnervation of the hamstrings only. We conclude that piriformis muscle surgery may be hazardous and result in devastating sciatic nerve injury.

  15. The Effect of Angipars on Diabetic Neuropathy in STZ-Induced Diabetic Male Rats: A Study on Behavioral, Electrophysiological, Sciatic Histological and Ultrastructural Indices

    PubMed Central

    Zangiabadi, Nasser; Mohtashami, Hossein; Hojatipour, Mahboobeh; Jafari, Mandana; Asadi-Shekaari, Majid; Shabani, Mohammad

    2014-01-01

    Diabetes mellitus is the most common metabolic disease with a high prevalence rate in human society that eventually leads to the peripheral nervous system complications in a great number of patients. In the present study, the effects of Angipars on nerve conduction velocity, histological alterations, and behavioral indices were investigated. Diabetes was induced in male rats by intraperitoneal injection of streptozotocin (STZ). Six weeks after STZ injection, animals were divided into five groups control, vehicle, and 3 experimental groups. The vehicle group received 1 mL distilled water daily for two weeks and three experimental groups received, respectively, intraperitoneal injection of 5, 10, and 20 mg/kg Angipars daily for two weeks. Intraperitoneal injection of Angipars, in some extent, could significantly improve behavioral indices of the experimental groups as compared to the vehicle group. Furthermore, mean nerve conduction velocity in the vehicle group showed significant difference with that in the control and the 2nd experimental groups; therefore, Angipars could increase nerve conduction velocity in neuropathic rats. Overall, Angipars exerted positive effects on the treatment and reduction of physiologic symptoms and improvement of sciatic morphological injuries in neuropathic rats. PMID:25614895

  16. Sciatic nerve injury caused by a stretching exercise in a trained dancer.

    PubMed

    Shim, Ho Yong; Lim, Oh Kyung; Bae, Keun Hwan; Park, Seok Min; Lee, Ju Kang; Park, Ki Deok

    2013-12-01

    Sciatic nerve injury after stretching exercise is uncommon. We report a case of an 18-year-old female trained dancer who developed sciatic neuropathy primarily involving the tibial division after routine stretching exercise. The patient presented with dysesthesia and weakness of the right foot during dorsiflexion and plantarflexion. The mechanism of sciatic nerve injury could be thought as hyperstretching alone, not caused by both hyperstretching and compression. Electrodiagnostic tests and magnetic resonance imaging revealed evidence of the right sciatic neuropathy from the gluteal fold to the distal tibial area, and partial tear of the left hamstring origin and fluid collection between the left hamstring and ischium without left sciatic nerve injury. Recovery of motor weakness was obtained by continuous rehabilitation therapy and some evidence of axonal regeneration was obtained by follow-up electrodiagnostic testing performed at 3, 5, and 12 months after injury.

  17. [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.

  18. [Buttocks sciatic pain].

    PubMed

    Labat, J-J; Robert, R; Riant, T; Louppe, J-M; Lucas, O; Hamel, O

    2009-10-01

    Confusion between radicular and nerve trunk syndrome is not rare. With sciatic pain, any nerve trunk pain or an atypical nerve course should suggest nerve trunk pain of the sciatic nerve in the buttocks. The usual reflex with sciatic pain is vertebral-radicular conflict. The absence of spinal symptoms and the beginning of pain in the buttocks and not in the lumbar region should reorient the etiologic search. Once a tumor of the nerve trunk has been ruled out (rarely responsible for pain other than that caused by tumor pressure), a myofascial syndrome should be explored searching for clinical, electrophysiological, and radiological evidence of compression of the sciatic trunk by the piriform muscle but also the obturator internus muscle. Hamstring syndrome may be confused with this syndrome. Treatment is first and foremost physical therapy. Failures can be treated with classical CT-guided infiltrations with botulinum toxin. Surgery should only be entertained when all these solutions have failed.

  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. Peripheral Neuropathy

    MedlinePlus

    Peripheral neuropathy Overview By Mayo Clinic Staff Peripheral neuropathy, a result of damage to your peripheral nerves, often causes weakness, numbness and pain, usually in your hands and feet. It can also ...

  1. Diabetic Neuropathy

    MedlinePlus

    ... of diabetic neuropathy may become severe enough to cause depression in some patients. × Prognosis The prognosis for diabetic ... of diabetic neuropathy may become severe enough to cause depression in some patients. View Full Prognosis Clinical Trials ...

  2. Diabetic neuropathy

    PubMed Central

    Bansal, V; Kalita, J; Misra, U K

    2006-01-01

    Diabetic neuropathy (DN) refers to symptoms and signs of neuropathy in a patient with diabetes in whom other causes of neuropathy have been excluded. Distal symmetrical neuropathy is the commonest accounting for 75% DN. Asymmetrical neuropathies may involve cranial nerves, thoracic or limb nerves; are of acute onset resulting from ischaemic infarction of vasa nervosa. Asymmetric neuropathies in diabetic patients should be investigated for entrapment neuropathy. Diabetic amyotrophy, initially considered to result from metabolic changes, and later ischaemia, is now attributed to immunological changes. For diagnosis of DN, symptoms, signs, quantitative sensory testing, nerve conduction study, and autonomic testing are used; and two of these five are recommended for clinical diagnosis. Management of DN includes control of hyperglycaemia, other cardiovascular risk factors; α lipoic acid and L carnitine. For neuropathic pain, analgesics, non‐steroidal anti‐inflammatory drugs, antidepressants, and anticonvulsants are recommended. The treatment of autonomic neuropathy is symptomatic. PMID:16461471

  3. 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 ...

  4. Vasculitic neuropathy.

    PubMed

    Sampaio, Luzia; Silva, Lã Gia; Terroso, Georgina; Nadais, Goreti; Mariz, Eva; Ventura, Francisco

    2011-01-01

    Vasculitic neuropathy corresponds to the occurrence of vasculitis at the level of vasa nervorum, resulting in ischemic damage of the peripheral nerve and axonal degeneration. Vasculitic neuropathy commonly occurs in association with systemic diseases and may be the initial manifestation or arise in the course of established disease. Although rare, vasculitis can be confined to the peripheral nervous system - non-systemic vasculitic neuropathy. This paper aims to review the classification, diagnosis and treatment of vasculitic neuropathy.

  5. Decompression of the Sciatic Nerve Entrapment Caused by Post-Inflammatory Scarring

    PubMed Central

    Kim, Deog-ryeong; Jeun, Sin Soo; Lee, Sang-won

    2015-01-01

    A rare case of chronic pain of entrapment neuropathy of the sciatic nerve successfully relieved by surgical decompression is presented. A 71-year-old male suffered a chronic right buttock pain of duration of 7 years which radiating to the right distal leg and foot. His pain developed gradually over one year after underwenting drainage for the gluteal abscess seven years ago. A cramping buttock and intermittently radiating pain to his right foot on sitting, walking, and voiding did not respond to conventional treatment. An MRI suggested a post-inflammatory adhesion encroaching the proximal course of the sciatic nerve beneath the piriformis as it emerges from the sciatic notch. Upon exploration of the sciatic nerve, a fibrotic tendinous scar beneath the piriformis was found and released proximally to the sciatic notch. His chronic intractable pain was completely relieved within days after the decompression. However, thigh weakness and hypesthesia of the foot did not improve. This case suggest a need for of more prompt investigation and decompression of the chronic sciatic entrapment neuropathy which does not improve clinically or electrically over several months. PMID:25733994

  6. Sciatic nerve hypertrophy with Klippel-Trenaunay syndrome: a case report.

    PubMed

    Ilhanli, Ilker; Keskin, Ozlem; Arslan, Erhan; Ekiz, Mehmet

    2015-01-01

    A 73-year-old female patient who had severe neuropathic pain due to sciatic nerve hypertrophy with the Klippel-Trenaunay Syndrome has been presented. Localized hypertrophic neuropathy is in one region and characterized by concentric proliferation of Schwann cells around the axon. It is very rare in the absence of generalized hypertrophic neuropathy. Very little is known about the etiology and the course of this neuropathy. Klippel-Trenaunay-Syndrome (KTS) is a rare syndrome characterized by hemangioma, abnormalities of the venous and lymphatic systems, and limb enlargement due to soft tissue and bone hypertrophy.

  7. Inflammatory neuropathies.

    PubMed

    Whitesell, Jackie

    2010-09-01

    Inflammatory neuropathies are acquired disorders of peripheral nerves and occasionally of the central nervous system that can affect individuals at any age. The course can be monophasic, relapsing, or progressive. Inflammatory neuropathies are classified as acute or chronic. The acute form reaches a nadir by 4 weeks and the chronic form over 8 weeks or greater. The most common example of an acute inflammatory neuropathy is acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is part of the Guillain-Barré syndrome (GBS). The most common chronic inflammatory neuropathy is chronic inflammatory demyelinating polyradiculopathy (CIDP). Other chronic inflammatory neuropathies are multifocal motor neuropathy (MMN) and the Lewis-Sumner syndrome. The Fisher syndrome and Bickerstaff brainstem encephalitis occur acutely and have clinical overlap with AIDP.

  8. AMYLOID NEUROPATHIES

    PubMed Central

    Shin, Susan C.; Robinson-Papp, Jessica

    2012-01-01

    Peripheral neuropathy is a common complication of many of the systemic amyloidoses. Although the cause of neuropathy is not entirely clear, it is likely related to amyloid deposition within the nerve. This may lead to focal, multifocal, or diffuse neuropathies involving sensory, motor and/or autonomic fibers. The presenting symptoms depend on the distribution of nerves affected. One of the most common phenotypes is sensorimotor polyneuropathy, which is characterized by symptoms of neuropathic pain, numbness, and in advanced cases weakness. Symptoms begin in the feet and ultimately progress to the proximal legs and hands. The most common focal neuropathy is a median neuropathy at the wrist, or clinically known as carpal tunnel syndrome. Carpal tunnel symptoms may include pain and sensory disturbances in the lateral palm and fingers; hand weakness may ensue if the focal neuropathy is severe. Autonomic neuropathy may affect a variety of organ systems such as the cardiovascular, gastrointestinal, and genitourinary systems. Symptoms may be non-specific making the diagnosis of autonomic neuropathy more difficult to identify. However, it is important to recognize and distinguish autonomic neuropathy from diseases of the end-organs themselves. This chapter reviews the inherited and acquired amyloidoses that affect the peripheral nervous system including familial amyloid polyneuropathy, and primary, secondary and senile amyloidosis. We emphasize the clinical presentation of the neurologic aspects of these diseases, physical examination findings, appropriate diagnostic evaluation, treatment and prognosis. PMID:23239211

  9. Delayed Presentation of Sciatic Nerve Injury after Total Hip Arthroplasty: Neurosurgical Considerations, Diagnosis, and Management

    PubMed Central

    Xu, Linda W.; Veeravagu, Anand; Azad, Tej D.; Harraher, Ciara; Ratliff, John K.

    2016-01-01

    Background  Total hip arthroplasty (THA) is an established treatment for end-stage arthritis, congenital deformity, and trauma with good long-term clinical and functional outcomes. Delayed sciatic nerve injury is a rare complication after THA that requires prompt diagnosis and management. Methods  We present a case of sciatic nerve motor and sensory deficit in a 52-year-old patient 2 years after index left THA. Electromyography (EMG) results and imaging with radiographs and CT of the affected hip demonstrated an aberrant acetabular cup screw in the posterior-inferior quadrant adjacent to the sciatic nerve. Case Description  The patient underwent surgical exploration that revealed injury to the peroneal division of the sciatic nerve due to direct injury from screw impingement. A literature review identified 11 patients with late-onset neuropathy after THA. Ten patients underwent surgical exploration and pain often resolved after surgery with 56% of patients recovering sensory function and 25% experiencing full recovery of motor function. Conclusions  Delayed neuropathy of the sciatic nerve is a rare complication after THA that is most often due to hardware irritation, component failure, or wear-related pseudotumor formation. Operative intervention is often pursued to explore and directly visualize the nerve with limited results in the literature showing modest relief of pain and sensory symptoms and poor restoration of motor function. PMID:27602309

  10. Endoscopic Sciatic Neurolysis.

    PubMed

    Knudsen, Joshua S; McConkey, Mark O; Brick, Matthew J

    2015-08-01

    Despite remaining a controversial diagnosis, piriformis syndrome continues to affect patients' quality of life with pain, sitting discomfort, and exercise intolerance. Open sciatic neurolysis has been noted by the senior author to often only bring temporary relief of the symptoms, with the recurrence presumably due to postoperative scar tissue. Minimally invasive techniques used to decompress the nerve have met with mixed results. This article describes a step-by-step surgical technique designed to maximize patient safety, as well as surgeon orientation, and achieve a thorough neurolysis. Preoperative findings suggestive of piriformis syndrome are described and include retro-trochanteric pain, sciatica-like leg pain, and paresthesias, as well as a positive response to computed tomography-guided injection of dilute ropivacaine hydrochloride and 40 mg of triamcinolone. The operation is performed with the patient in the lateral decubitus position through 2 portals 6 to 8 cm apart, allowing for good triangulation. Dissection is undertaken with a combination of radiofrequency and a laparoscopic peanut, with the assistance of a vascular sling to control the sciatic nerve. Encouraging results have been achieved, and with increasing interest in this procedure, a step-by-step technical description with an accompanying video may prove useful for other experienced hip arthroscopists. Pearls and pitfalls are discussed.

  11. Endoscopic Sciatic Neurolysis

    PubMed Central

    Knudsen, Joshua S.; McConkey, Mark O.; Brick, Matthew J.

    2015-01-01

    Despite remaining a controversial diagnosis, piriformis syndrome continues to affect patients' quality of life with pain, sitting discomfort, and exercise intolerance. Open sciatic neurolysis has been noted by the senior author to often only bring temporary relief of the symptoms, with the recurrence presumably due to postoperative scar tissue. Minimally invasive techniques used to decompress the nerve have met with mixed results. This article describes a step-by-step surgical technique designed to maximize patient safety, as well as surgeon orientation, and achieve a thorough neurolysis. Preoperative findings suggestive of piriformis syndrome are described and include retro-trochanteric pain, sciatica-like leg pain, and paresthesias, as well as a positive response to computed tomography–guided injection of dilute ropivacaine hydrochloride and 40 mg of triamcinolone. The operation is performed with the patient in the lateral decubitus position through 2 portals 6 to 8 cm apart, allowing for good triangulation. Dissection is undertaken with a combination of radiofrequency and a laparoscopic peanut, with the assistance of a vascular sling to control the sciatic nerve. Encouraging results have been achieved, and with increasing interest in this procedure, a step-by-step technical description with an accompanying video may prove useful for other experienced hip arthroscopists. Pearls and pitfalls are discussed. PMID:26759776

  12. 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.

  13. Diabetic neuropathy.

    PubMed

    Said, Gérard

    2013-01-01

    Diabetes is the most common cause of peripheral neuropathy in the world. Both type 1 (insulin-dependent) and type 2 diabetes are commonly complicated by peripheral nerve disorders. Two main types of neuropathy are observed: the most common is a nerve fiber length-dependent, distal symmetrical sensory polyneuropathy with little motor involvement but frequent, and potentially life threatening, autonomic dysfunction. Alteration of temperature and pain sensations in the feet is an early manifestation of diabetic polyneuropathy. The second pattern is a focal neuropathy, which more commonly complicates or reveals type 2 diabetes. Poor diabetic control increases the risk of neuropathy with subsequent neuropathic pains and trophic changes in the feet, which can be prevented by education of patients.

  14. Autonomic neuropathy

    MedlinePlus

    ... page, please enable JavaScript. Autonomic neuropathy is a group of symptoms that occur when there is damage to the nerves that manage every day body functions such as blood pressure, heart rate, sweating, bowel and bladder emptying, and ...

  15. Peripheral neuropathy

    MedlinePlus

    ... damage your nerves. Other health conditions that may cause neuropathy are: Autoimmune disorders, such as rheumatoid arthritis or lupus Chronic kidney disease Infections such as HIV/AIDS, shingles , hepatitis C ...

  16. Paraneoplastic neuropathy.

    PubMed

    Koike, Haruki; Sobue, Gen

    2013-01-01

    Recent progress in serological screening of paraneoplastic antibodies and in diagnostic imaging techniques to detect malignancies has enabled a broadening of the concept of paraneoplastic neurological syndromes by integrating nonclassic clinical features. The peripheral nervous system is frequently involved in patients with paraneoplastic syndrome and may be seen alone or in combination with involvement of other areas of the nervous system. Destruction of dorsal root ganglion cells due to lymphocytic infiltration, especially with CD8-positive cytotoxic T cells, has been postulated to mediate the classic syndrome of subacute sensory neuronopathy. However, the motor and autonomic nervous systems are frequently affected. Indeed, patients can develop clinical features compatible with Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, or brachial plexopathy. Other forms of paraneoplastic neuropathy are vasculitic neuropathy, autoimmune autonomic ganglionopathy, and chronic intestinal pseudo-obstruction. Various onconeural antibodies, including anti-Hu, anti-CV2/CRMP-5, and anti-ganglionic acetylcholine receptor antibodies, are associated with neuropathy. Somatic neuropathy is the most common manifestation in patients with anti-Hu and anti-CV2/CRMP-5 antibodies, while anti-ganglionic acetylcholine receptor antibody is associated with autonomic neuropathies. A whole-body fluorodeoxyglucose positron emission tomography scan may be useful to detect malignancy in patients with unremarkable conventional radiological findings. Recognition and diagnosis of paraneoplastic neuropathy is important, as neuropathic symptoms usually precede the identification of the primary tumor, and treatment at an earlier stage provides better chances of good outcomes.

  17. 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

  18. Galanin and its receptor system promote the repair of injured sciatic nerves in diabetic rats

    PubMed Central

    Xu, Xiao-feng; Zhang, Dan-dan; Liao, Jin-chi; Xiao, Li; Wang, Qing; Qiu, Wei

    2016-01-01

    Various studies have reported that galanin can promote axonal regeneration of dorsal root ganglion neurons in vitro and inhibit neuropathic pain. However, little is known about its effects on diabetic peripheral neuropathy, and in vivo experimental data are lacking. We hypothesized that repeated applications of exogenous galanin over an extended time frame may also repair nerve damage in diabetic peripheral neuropathy, and relieve pain in vivo. We found that neuropathic pain occurred in streptozotocin-induced diabetic rats and was more severe after sciatic nerve pinch injury at 14 and 28 days than in diabetic sham-operated rats. Treatment with exogenous galanin alleviated the neuropathic pain and promoted sciatic nerve regeneration more effectively in diabetic rats than in non-diabetic rats after sciatic nerve pinch injury. This was accompanied by changes in the levels of endogenous galanin, and its receptors galanin receptor 1 and galanin receptor 2 in the dorsal root ganglia and the spinal dorsal horn when compared with nerve pinch normal rats. Our results show that application of exogenous galanin daily for 28 days can promote the regeneration of injured sciatic nerves, and alleviate neuropathic pain in diabetic rats. PMID:27857760

  19. A conduction block in sciatic nerves can be detected by magnetic motor root stimulation.

    PubMed

    Matsumoto, Hideyuki; Konoma, Yuko; Fujii, Kengo; Hanajima, Ritsuko; Terao, Yasuo; Ugawa, Yoshikazu

    2013-08-15

    Useful diagnostic techniques for the acute phase of sciatic nerve palsy, an entrapment neuropathy, are not well established. The aim of this paper is to demonstrate the diagnostic utility of magnetic sacral motor root stimulation for sciatic nerve palsy. We analyzed the peripheral nerves innervating the abductor hallucis muscle using both electrical stimulations at the ankle and knee and magnetic stimulations at the neuro-foramina and conus medullaris levels in a patient with sciatic nerve palsy at the level of the piriformis muscle due to gluteal compression related to alcohol consumption. On the fourth day after onset, magnetic sacral motor root stimulation using a MATS coil (the MATS coil stimulation method) clearly revealed a conduction block between the knee and the sacral neuro-foramina. Two weeks after onset, needle electromyography supported the existence of the focal lesion. The MATS coil stimulation method clearly revealed a conduction block in the sciatic nerve and is therefore a useful diagnostic tool for the abnormal neurophysiological findings associated with sciatic nerve palsy even at the acute phase.

  20. Diabetic Neuropathy

    PubMed Central

    Gibbons, Christopher H.; Freeman, Roy; Veves, Aristidis

    2010-01-01

    OBJECTIVE To determine the relationships among large, small, and autonomic fiber neurophysiological measures in a cross-sectional study of patients with diabetes. RESEARCH DESIGN AND METHODS We assessed 130 individuals: 25 healthy subjects and 105 subjects with diabetes. Subjects were classified by the presence or absence of neuropathy by physical examination. All subjects underwent autonomic testing, nerve conduction studies, quantitative sensory testing, and nerve-axon reflex vasodilation in addition to quantifiable neurological examination and symptom scores. Correlation and cluster analysis were used to determine relationships between and among different neurophysiological testing parameters. RESULTS Results of neurophysiological tests were abnormal in patients with clinical evidence of diabetic neuropathy compared with results in healthy control subjects and in those without neuropathy (P < 0.01, all tests). The correlations among individual tests varied widely, both within (r range <0.5–>0.9, NS to <0.001) and between test groups (r range <0.2–>0.5, NS to <0.01). A two-step hierarchical cluster analysis revealed that neurophysiological tests do not aggregate by typical “small,” “large,” or “autonomic” nerve fiber subtypes. CONCLUSIONS The modest correlation coefficients seen between the different testing modalities suggest that these techniques measure different neurophysiological parameters and are therefore not interchangeable. However, the data suggest that only a small number of neurophysiological tests are actually required to clinically differentiate individuals with neuropathy from those without. The natural clustering of both patients and healthy control subjects suggests that variations in the population will need to be considered in future studies of diabetic neuropathy. PMID:20805259

  1. Acquired inflammatory demyelinating neuropathies.

    PubMed

    Ensrud, E R; Krivickas, L S

    2001-05-01

    The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

  2. Effects of decompression on behavioral, electrophysiologic, and histomorphologic recovery in a chronic sciatic nerve compression model of streptozotocin-induced diabetic rats

    PubMed Central

    Wang, Ping-Hui; Yang, Cheng-Chang; Su, Wei-Ren; Wu, Po-Ting; Cheng, Shun-Chien; Jou, I-Ming

    2017-01-01

    Purpose To determine susceptibility to decompression surgery in diabetic and nondiabetic peripheral neuropathy using a chronic compression neuropathy model. Materials and methods Twenty-four streptozotocin-induced diabetic rats were randomly divided into three groups: group I, chronic compression of the left sciatic nerve for 4 weeks with decompression; group II, similar without decompression; and group III, sham exposing the sciatic nerve only. The other 24 nondiabetic rats were assigned to groups IV–VI, which received compression–decompression, compression, and the sham operation, respectively. Mixed-nerve-elicited somatosensory evoked potentials (M-SSEPs) and compound muscle action potentials (CMAPs) were measured to verify the compression neuropathy in the posttreatment follow-up. Behavioral observations in thermal hyperalgesia tests were quantified before electrophysiologic examinations. Treated and contralateral nerves were harvested for histomorphologic analysis. Results Chronic compression of sciatic nerve induced significant reduction of amplitude and increment of latency of M-SSEP and CMAP in both diabetic and nondiabetic rats. Diabetic group changes were more susceptible. Decompression surgery significantly improved both sensory and motor conduction, thermal hyperalgesia, and the mean myelin diameter of the rat sciatic nerve in both diabetic and nondiabetic groups. Near full recovery of motor and sensory function occurred in the nondiabetic rats, but not in the diabetic rats 8 weeks postdecompression. Conclusion Behavioral, electrophysiologic, and histomorphologic findings indicate that decompression surgery is effective in both diabetic and nondiabetic peripheral neuropathy. PMID:28360533

  3. Enhanced synthesis and secretion of apolipoprotein E from sciatic nerves of streptozotocin-induced diabetic rats after injury

    SciTech Connect

    Ishibashi, S.; Yamada, N.; Oka, Y.; Shimano, H.; Mori, N.; Yoon, T.H.; Shimada, M.; Kanazawa, Y.; Akanuma, Y.; Murase, T.

    1988-08-30

    To elucidate the pathogenesis of diabetic neuropathy, synthesis and secretion of apolipoprotein E (apo E) from sciatic nerves after injury was studied in normal and streptozotocin-induced diabetic rats. Seven, 14, 28, 45 and 59 days after making crush injury on sciatic nerves with concomitant administration of streptozotocin (50 mg/kg body weight), the nerves were taken out and incubated with (/sup 35/S)methionine. The (/sup 35/S)labeled apo E was precipitated with specific antiserum. The amounts of apo E secreted into medium by nerves of diabetic rats were 7 times greater than those of non-diabetic rats 7 days after injury. This enhanced secretion of apo E was relatively selective for this protein, since the ratio of the immunoprecipitable apo E to the TCA preciptitable protein in the medium increased in diabetic rats. Intriguing possibility deduced from these results is that the secretion of apo E is involved in the development of diabetic neuropathy.

  4. [Inflammatory neuropathies and multineuritis].

    PubMed

    Kuntzer, Thierry; Chofflon, Michel

    2009-12-02

    Inflammatory neuropathies include those neuropathies in which the diagnosis, outcome and type of treatment are badly known, the reason of this review. They are expressed as diffuse (such as CIDP and ganglionopathies), multifocal (vasculitic neuropathy) or focal (MMN; plexopathies; immune reconstitution inflammatory syndrome). These forms of neuropathies are important to be known because the beneficial therapeutic possibilities of immunosuppression.

  5. 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.

  6. Mitotoxicity and bortezomib-induced chronic painful peripheral neuropathy.

    PubMed

    Zheng, H; Xiao, W H; Bennett, G J

    2012-12-01

    Many of the most effective anti-cancer drugs induce a dose-limiting peripheral neuropathy that compromises therapy. Evidence from animal models of chemotherapy-induced painful peripheral neuropathy produced by the taxane agent, paclitaxel, and the platinum-complex agent, oxaliplatin, indicate that they produce neuropathy via a common mechanism-a toxic effect on the mitochondria in primary afferent sensory neurons. Bortezomib is from the proteasome-inhibitor class of chemotherapeutics. It also produces a dose-limiting peripheral neuropathy, but its effects on neuronal mitochondria are unknown. To investigate this, we developed a model of bortezomib-induced painful peripheral neuropathy in the rat and assessed mitochondrial function (respiration and ATP production) in sciatic nerve samples harvested at two time points: day 7, which is three days after treatment and before pain appears, and day 35, which is one month post-treatment and the time of peak pain severity. We found significant deficits in Complex I-mediated and Complex II-mediated respiration, and in ATP production at both time points. Prophylactic treatment with acetyl-L-carnitine, which has previously been shown to prevent paclitaxel- and oxaliplatin-induced mitochondrial dysfunction and pain, completely blocked bortezomib's effects on mitochondria and pain. These results suggest that mitotoxicity may be the core pathology for all chemotherapy-induced peripheral neuropathy and that drugs that protect mitochondrial function may be useful chemotherapy adjuncts.

  7. Peripheral neuropathy in diabetes.

    PubMed

    Majumder, A; Chatterjee, S; Maji, D

    2013-06-01

    Peripheral neuropathy is common complication of diabetes. The prevalence of peripheral neuropathy among diabetic patients on the basis of loss of vibration sensation had been studied. Detailed clinical history of each patient including age, gender, duration of diabetes, foot ulcer and biothesiometry was recorded in 211 diabetic patients between 20 and 80 years of age. It was observed that all patients under 30 years age (n = 8) felt vibration below 15 volts (no risk zone); 77% (24 out of 31) of the patients in the age group of 30-39 years were in the no risk zone, and 23% (n = 7) had mild peripheral neuropathy. Sixty per cent of the patients between 40 and 50 years (n = 44) were in the no risk zone, while 32% (n = 24) had mild peripheral neuropathy, 5% (n = 4) had moderate neuropathy and 3% (n = 2) had severe peripheral neuropathy. Amongst patients above 50 years of age, 31% (n = 31) were in no risk zone, 34% (n = 34) had mild peripheral neuropathy, 22% (n = 20) had moderate peripheral neuropathy and 13% (n = 13) had severe peripheral neuropathy. Of the patients with diabetes for less than 5 years, 58% had no neuropathy, and only 3% had severe neuropathy. Of the patients with diabetes for 5 to 15 years, 50% had no neuropathy, 30% had mild, and 10% had severe peripheral neuropathy. When patients with diabetes for over 15 years were studied, only 6% had no neuropathy and 19% had severe peripheral neuropathy. The study re-establishes that the severity of peripheral neuropathy increases with age and vibration perception decreses progressively with increased duration of diabetes. Vibration perception threshold testing helps to identify the high risk subjects who require special counselling and education to protect their feet.

  8. Tetrahydrocurcumin exerts protective effect on vincristine induced neuropathy: Behavioral, biochemical, neurophysiological and histological evidence.

    PubMed

    Greeshma, N; Prasanth, K G; Balaji, Bhaskar

    2015-08-05

    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.

  9. Sciatic nerve: beyond the sacral foramen

    PubMed Central

    Sanal, Hatice Tuba

    2016-01-01

    Sciatica may result from pathologies affecting the nerve both in its intraspinal and extraspinal course. In daily routine, the vast majority of cases are caused by herniation of the lumbar discs compressing the neural roots. Extraspinal causes of sciatic pain are usually underestimated and the imaging study may be completed after reporting the lumbar MRIs. However, early diagnosis of the exact etiology of sciatica is paramount for both relieving the symptoms and preventing any additional neurologic injury. In this pictorial assay, some relatively rare causes of sciatic neuralgia along the route of the sciatic nerve after leaving the sacral foramen will be displayed. PMID:27670092

  10. Peripheral neuropathies 1988

    SciTech Connect

    Assal, J.P.; Liniger, C.

    1990-01-01

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

  11. Dumb-bell shaped tuberculous abscess across the greater sciatic notch compressing both sciatic nerves.

    PubMed

    Baba, H; Okumura, Y; Furusawa, N; Omori, H; Kawahara, H; Fujita, T; Katayama, K; Noriki, S

    1998-08-01

    We report an instructive case of a 65-year-old man who presented with a dumb-bell shaped tuberculous abscess across the greater sciatic notch bilaterally compressing both sciatic nerves. Clinical symptoms progressed slowly and mimicked lumbar radiculopathy, thus delaying an accurate diagnosis. Anterolateral retroperitoneal and posterolateral gluteal approaches of the greater sciatic notch as well as the acetabulum on both sides were followed in order to provide safe viewing and resection of the abscess. The abscess wall was adherent to the sciatic nerve and surrounding blood vessels. The symptoms completely disappeared after resection of the abscess.

  12. Piriformis Syndrome and Endoscopic Sciatic Neurolysis.

    PubMed

    Knudsen, Joshua S; Mei-Dan, Omer; Brick, Mathew J

    2016-03-01

    Piriformis syndrome is the compression or the irritation of the sciatic nerve by the adjacent piriformis muscle in the buttock leading to symptoms that include buttock pain, leg pain, and altered neurology in the sciatic nerve distribution. Epidemiological figures of the prevalence are unknown, but are estimated to be about 12.2% to 27%. There is no consensus on the diagnostic criteria. Advancement in magnetic resonance imaging allows us to observe unilateral hyperintensity and bowing of the sciatic nerve. The pathophysiology of the disease includes single blunt trauma, overuse causing piriformis hypertrophy, and long-term microtrauma causing scarring. Treatments include physiotherapy, steroid injections, and surgery. Minimally invasive techniques are emerging with the hope that with less postoperative scar tissue formation, there will be less recurrence of the disease. In this chapter, senior author describes his technique for endoscopic sciatic neurolysis.

  13. Sciatic nerve cuffing in mice: a model of sustained neuropathic pain.

    PubMed

    Benbouzid, Malika; Pallage, Viviane; Rajalu, Mathieu; Waltisperger, Elisabeth; Doridot, Stéphane; Poisbeau, Pierrick; Freund-Mercier, Marie José; Barrot, Michel

    2008-07-01

    Because of its severity, chronicity, resistance to usual therapy and its consequences on quality of life, neuropathic pain represents a real clinical challenge. Fundamental research on this pathology uses metabolic, pharmacological or traumatic models in rodents that reproduce the characteristic human pain symptoms. In 1996, Mosconi and Kruger morphologically described a model of peripheral neuropathy in which a cuff of polyethylene tubing was placed around the sciatic nerve in rats. In the present study, we evaluated the behavioral consequences of this neuropathic pain model in C57Bl/6J mice which is the main genetic background used for studies in transgenic mice. A short cuff of polyethylene tubing was unilaterally placed around the main branch of the sciatic nerve. It induced an ipsilateral heat thermal hyperalgesia lasting around 3 weeks, and a sustained ipsilateral mechanical allodynia lasting at least 2 months. We showed that this neuropathic pain model is insensitive to ketoprofen, a non-steroidal anti-inflammatory drug. Morphine treatment acutely suppressed the mechanical allodynia, but tolerance to this effect rapidly developed. The analysis of video recordings revealed that most aspects of spontaneous behavior remained unaffected on the long term, excepted for a decrease in the time spent at social interaction for the neuropathic mice. Using the elevated plus-maze and the marble-burying test, we also showed that neuropathic mice develop an anxiety phenotype. Our data indicate that sciatic nerve cuffing in mice is a pertinent model for the study of nociceptive and emotional consequences of sustained neuropathic pain.

  14. Peripheral Neuropathy and Agent Orange

    MedlinePlus

    ... ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  15. Cardiac Involvement in Peripheral Neuropathies.

    PubMed

    Burakgazi, Ahmet Z; AlMahameed, Soufian

    2016-03-01

    Cardiac autonomic neuropathy (CAN) is the least recognized and understood complication of peripheral neuropathy. However, because of its potential adverse effects including sudden death, CAN is one of the most important forms of autonomic neuropathies. CAN presents with different clinical manifestations including postural hypotension, exercise intolerance, fluctuation of blood pressure and heart rate, arrhythmia, and increased risk of myocardial infarction. In this article, the prevalence, clinical presentations, and management of cardiac involvement in certain peripheral neuropathies, including diabetic neuropathy, Guillain-Barré syndrome, chronic inflammatory polyneuropathy, human immunodeficiency virus-associated neuropathy, hereditary neuropathies, and amyloid neuropathy are examined in detail.

  16. Endoplasmic Reticulum Stress Plays a Key Role in the Pathogenesis of Diabetic Peripheral Neuropathy

    PubMed Central

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

    2013-01-01

    Endoplasmic reticulum stress resulting from abnormal folding of newly synthesized proteins impairs metabolism, transcriptional regulation, and gene expression, and it is a key mechanism of cell injury. Endoplasmic reticulum stress plays an important role in cardiovascular and neurodegenerative diseases, cancer, and diabetes. We evaluated the role for this phenomenon in diabetic peripheral neuropathy. Endoplasmic reticulum stress manifest in upregulation of multiple components of unfolded protein response was identified in neural tissues (sciatic nerve, spinal cord) of streptozotocin diabetic rats and mice. A chemical chaperone, trimethylamine oxide, administered for 12 weeks after induction of diabetes (110 mg⋅kg−1⋅d−1, a prevention paradigm) attenuated endoplasmic reticulum stress, peripheral nerve dysfunction, intraepidermal nerve fiber loss, and sciatic nerve and spinal cord oxidative-nitrative stress in streptozotocin diabetic rats. Similar effects on diabetes-induced endoplasmic reticulum stress and peripheral nerve dysfunction were observed with a structurally unrelated chemical chaperone, 4-phenylbutyric acid (100 mg⋅kg−1⋅d−1, intraperitoneal). CCAAT/enhancer-binding protein homologous protein (CHOP)−/− mice made diabetic with streptozotocin displayed less severe sciatic nerve oxidative-nitrative stress and peripheral neuropathy than the wild-type (C57Bl6/J) mice. Neither chemical chaperones nor CHOP gene deficiency reduced diabetic hyperglycemia. Our findings reveal an important role of endoplasmic reticulum stress in the development of diabetic peripheral neuropathy and identify a potential new therapeutic target. PMID:23364451

  17. 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

  18. Role of A3 adenosine receptor in diabetic neuropathy.

    PubMed

    Yan, Heng; Zhang, Enshui; Feng, Chang; Zhao, Xin

    2016-10-01

    Neuropathy is the most common diabetic complication. Although the A1 and A2A adenosine receptors are important pharmacological targets in alleviating diabetic neuropathy, the role of the A3 adenosine receptor remains unknown. Because the A3 adenosine receptor regulates pain induced by chronic constriction injury or chemotherapy, its stimulation might also attenuate diabetic neuropathy. This study examines the effects of systemic treatment with the A3 adenosine receptor agonist 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-β-d-ribofuranuronamide (IB-MECA) on diabetic neuropathy and explores the putative mechanisms underlying its pharmacological effects. We show that IB-MECA alleviated mechanical hyperalgesia and thermal hypoalgesia in mice 2 weeks but not 4 weeks after streptozocin (STZ) treatment. Furthermore, IB-MECA prevented the reduction in sciatic motor nerve conduction velocity and sensory nerve conduction velocity in diabetic mice 2 weeks but not 4 weeks after STZ treatment. Similarly, IB-MECA inhibited the activation of nuclear factor-κB and decreased the generation of tumor necrosis factor-α in the spinal cord of mice 2 weeks but not 4 weeks after STZ treatment. These phenomena were associated with reduction of A3 adenosine receptor expression in the spinal cord after long-term diabetes. Our results suggest that the A3 adenosine receptor plays a critical role in regulating diabetic neuropathy and that reduction in A3 adenosine receptor expression/function might contribute to the progression of diabetic neuropathy. © 2016 Wiley Periodicals, Inc.

  19. Study on Variant Anatomy of Sciatic Nerve

    PubMed Central

    V, Sangeetha

    2014-01-01

    Introduction: Sciatic Nerve (SN) is the nerve of the posterior compartment of thigh formed in the pelvis from the ventral rami of the L4 to S3 spinal nerves. It leaves the pelvis via the greater sciatic foramen below piriformis and divides into Common Peroneal Nerve (CPN) and Tibial Nerve (TN) at the level of the upper angle of the popliteal fossa. Higher division of the sciatic nerve is the most common variation where the TN and CPN may leave the pelvis through different routes. Such variation may lead to compression of the nerve and lead to Non-discogenic sciatica. Materials and Methods: Fifty lower limbs were used for the study from Department of Anatomy, J.J.M.M.C Davangere, Karnataka, India. Observation and Results: In our study on 25 cadavers (50 lower limbs), we have observed 4 (8 %) lower limbs high division of sciatic nerve was noted. High division of sciatic nerve in the back of thigh was noted in one specimen (2%), while high division within the pelvis was noted in 3 specimens (6%), while in 46 (92%) it occurred outside the pelvis. Conclusion: Knowledge regarding such variation and differences in the course of SN is important for the surgeons to plan for various surgical interventions pertaining to the gluteal region. The variant anatomy of SN may cause piriformis syndrome and failure of SN block. Hence present study is undertaken to know the level of division, exit, course, relationship to piriformis and variations in the branching pattern of SN. PMID:25302181

  20. Yoga neuropathy. A snoozer.

    PubMed

    Walker, Melanie; Meekins, Gregg; Hu, Shu-Ching

    2005-05-01

    Sciatic nerve compression very rarely occurs bilaterally. The authors present a woman with profound lower extremity weakness and sensory abnormality after falling asleep in the head-to-knees yoga position (also called "Paschimottanasana"). Clinical and electrodiagnostic findings are discussed in detail and a brief review of the literature is presented.

  1. Neuroprotective effects of octreotide on diabetic neuropathy in rats.

    PubMed

    Solmaz, Volkan; Çınar, Bilge Piri; Yiğittürk, Gürkan; Özlece, Hatice Köse; Avni Eroglu, Hüseyin; Tekatas, Aslan; Erbaş, Oytun; Taşkıran, Dilek

    2017-02-26

    The purpose of the present study is to investigate the possible healing effects of octreotide (OCT) on motor performance, electrophysiological and histopathological findings of diabetic neuropathy in a rat model of diabetes mellitus (DM). To induce diabetes, rats were administered a single dose (60mg/kg) of streptozotocin (STZ). Diabetic rats were treated either with saline (1ml/kg/day, n=7) or OCT (0.1mg/kg/day, n=7) for four weeks. Seven rats served as control group and received no treatment. At the end of the study, electromyography (EMG), gross motor function (inclined plate test), general histology and the perineural thickness of sciatic nerve were evaluated. At the end of study, weight loss was significantly lower in OCT treated rats than that of saline treated ones (p<0.001). Electrophysiologically, compound muscle action potential (CMAP) amplitudes of the saline treated DM group were significantly reduced than those of controls (p<0.0001). Also, distal latency and CMAP durations were significantly prolonged in saline treated DM group (p<0.05) compared to control. However, treatment of diabetic rats with OCT significantly counteracted these alterations in EMG. Furthermore, OCT significantly improved the motor performance scores in diabetic rats (p<0.05). Histomorphometric assessment of the sciatic nerve demonstrated a significant reduction in perineural thickness in OCT treated group compared to saline group. In conclusion, OCT possesses beneficial effects against STZ-induced diabetic neuropathy, which promisingly support the use of OCT as a neuroprotective agent in patients with diabetic neuropathy.

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

    PubMed

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

    2012-06-01

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

  3. Epalrestat: an aldose reductase inhibitor for the treatment of diabetic neuropathy.

    PubMed

    Ramirez, Mary Ann; Borja, Nancy L

    2008-05-01

    Diabetic neuropathy is one of the most common long-term complications in patients with diabetes mellitus, with a prevalence of 60-70% in the United States. Treatment options include antidepressants, anticonvulsants, tramadol, and capsaicin. These agents are modestly effective for symptomatic relief, but they do not affect the underlying pathology nor do they slow progression of the disease. Epalrestat is an aldose reductase inhibitor that is approved in Japan for the improvement of subjective neuropathy symptoms, abnormality of vibration sense, and abnormal changes in heart beat associated with diabetic peripheral neuropathy. Unlike the current treatment options for diabetic neuropathy, epalrestat may affect or delay progression of the underlying disease process. Data from experimental studies indicate that epalrestat reduces sorbitol accumulation in the sciatic nerve, erythrocytes, and ocular tissues in animals, and in erythrocytes in humans. Data from six clinical trials were evaluated, and it was determined that epalrestat 50 mg 3 times/day may improve motor and sensory nerve conduction velocity and subjective neuropathy symptoms as compared with baseline and placebo. Epalrestat is well tolerated, and the most frequently reported adverse effects include elevations in liver enzyme levels and gastrointestinal-related events such as nausea and vomiting. Epalrestat may serve as a new therapeutic option to prevent or slow the progression of diabetic neuropathy. Long-term, comparative studies in diverse patient populations are needed for clinical application.

  4. 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.

  5. Painful diabetic neuropathy.

    PubMed

    Peltier, Amanda; Goutman, Stephen A; Callaghan, Brian C

    2014-05-06

    Diabetes is a worldwide epidemic, and associated neuropathy is its most costly and disabling complication. Given the rising prevalence of painful diabetic neuropathy, it is increasingly important that we understand the best ways to diagnose and treat this condition. Diagnostic tests in this field are evolving rapidly. These include the use of skin biopsies to measure small unmyelinated fibers, as well as even newer techniques that can measure both small unmyelinated fibers and large myelinated fibers in the same biopsy. The main treatments for painful diabetic neuropathy remain management of the underlying diabetes and drugs for the relief of pain. However, emerging evidence points to major differences between type 1 and type 2 diabetes, including the ability of glycemic control to prevent neuropathy. Enhanced glucose control is much more effective at preventing neuropathy in patients with type 1 diabetes than in those with type 2 disease [corrected]. This dichotomy emphasizes the need to study the pathophysiologic differences between the two types of diabetes, because different treatments may be needed for each condition. The impact of the metabolic syndrome on neuropathy in patients with type 2 diabetes may account for the difference between the two types of diabetes and requires further study. Finally, neuropathic pain is under-recognized and undertreated despite an ever evolving list of effective drugs. Evidence exists to support several drugs, but the optimal sequence and combination of these drugs are still to be determined.

  6. Peripheral Neuropathy: Prevention and Treatment.

    DTIC Science & Technology

    AChE, BuChE, neurotoxic esterase, carboxylesterase). Likewise, there were no changes in the compound action potential of either the sural or sciatic...nerve and no changes in the sciatic nerve responsiveness to extracellular potassium. The triceps surae muscles responded normally to tetanic

  7. 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

  8. Treatment of proximal hamstring tendinopathy-related sciatic nerve entrapment: presentation of an ultrasound-guided “Intratissue Percutaneous Electrolysis” application

    PubMed Central

    Mattiussi, Gabriele; Moreno, Carlos

    2016-01-01

    Summary Background Proximal Hamstring Tendinopathy-related Sciatic Nerve Entrapment (PHTrSNE) is a neuropathy caused by fibrosis interposed between the semimembranosus tendon and the sciatic nerve, at the level of the ischial tuberosity. Methods Ultrasound-guided Intratissue Percutaneous Electrolysis (US-guided EPI) involves galvanic current transfer within the treatment target tissue (fibrosis) via a needle 0.30 to 0.33 mm in diameter. The galvanic current in a saline solution instantly develops the chemical process of electrolysis, which in turn induces electrochemical ablation of fibrosis. In this article, the interventional procedure is presented in detail, and both the strengths and limits of the technique are discussed. Results US-guided EPI eliminates the fibrotic accumulation that causes PHTrSNE, without the semimembranosus tendon or the sciatic nerve being directly involved during the procedure. The technique is however of limited use in cases of compression neuropathy. Conclusion US-guided EPI is a technique that is quick to perform, minimally invasive and does not force the patient to suspend their activities (work or sports) to make the treatment effective. This, coupled to the fact that the technique is generally well-tolerated by patients, supports use of US-guided EPI in the treatment of PHTrSNE. PMID:27900300

  9. [Effects of Tongxinluo capsule on sciatic nerve apoptosis in spontaneous type II diabetic KK/Upj-Ay mice and mechanism research].

    PubMed

    Wang, Chao; Zhang, Hui-xin; Xing, Han-ying; Wang, Xing

    2015-04-01

    To investigate the effects of Tongxinluo capsule on sciatic nerve apoptosis in spontaneous type II diabetic KK/Upj-Ay mice, in order to explore its mechanism for improving diabetic peripheral neuropathy (DPN). KK/Upj-Ay mice were selected as the DPN animal model and randomly divided into the model, Tongxinluo low, middle and high group (1, 2, 4 g x kg(-1)). C57BL/6 mice were selected as the control group. Mice were given intragastrically for 12 weeks. Paw withdrawal latency, motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) were detected. Apoptotic rate were detected by FCM. Bcl-2, Bax, Caspase-3 mRNA and protein expression in sciatic nerve were examined by Real-time PCR and Western blot. p38MAPK, p-p38MAPK expression were examined by Western blot. In this study,the authors found that Tongxinluo capsule could increase paw withdrawal latency, MNCV and SNCV. Apoptotic rate of sciatic, the expression of Bax and caspase-3 were lower, while Bcl-2 expression was higher in Tongxinluo group than those in model mice. The expression of p-p38MAPK significantly decreased in Tongxinluo group. The results showed that Tongxinluo capsule has protective effects on diabetic peripheral neuropathy of mice via inhibiting cell apoptosis and suppressing the expression of p-p38MAPK.

  10. 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

  11. Pathogenesis of diabetic neuropathy: bad to the bone.

    PubMed

    Chan, Lawrence; Terashima, Tomoya; Urabe, Hiroshi; Lin, Fan; Kojima, Hideto

    2011-12-01

    Insulin and proinsulin are normally produced only by the pancreas and thymus. We detected in diabetic rodents the presence of extra pancreatic proinsulin-producing bone marrow-derived cells (PI-BMDCs) in the BM, liver, and fat. In mice and rats with diabetic neuropathy, we also found proinsulin-producing cells in the sciatic nerve and neurons of the dorsal root ganglion (DRG). BM transplantation experiments using genetically marked donor and recipient mice showed that the proinsulin-producing cells in the DRG, which morphologically resemble neurons, are actually polyploid proinsulin-producing fusion cells formed between neurons and PI-BMDCs. Additional experiments indicate that diabetic neuropathy is not simply the result of nerve cells being damaged directly by hyperglycemia. Rather, hyperglycemia induces fusogenic PI-BMDCs that travel to the peripheral nervous system, where they fuse with Schwann cells and DRG neurons, causing neuronal dysfunction and death, the sine qua non for diabetic neuropathy. Poorly controlled diabetes is indeed bad to the bone.

  12. Peripheral Neuropathy: Symptoms and Signs

    MedlinePlus

    ... Tomography Scan (CAT) Electrodiagnostic Testing Lumbar Puncture Imaging Quantitative Sensory Testing (QST) Peripheral Neuropathy Treatments Facts + Risk ... Tomography Scan (CAT) Electrodiagnostic Testing Lumbar Puncture Imaging Quantitative Sensory Testing (QST) Peripheral Neuropathy Treatments Facts + Risk ...

  13. Neuropathy and monoclonal gammopathy.

    PubMed

    Nobile-Orazio, Eduardo

    2013-01-01

    The association of neuropathy with monoclonal gammopathy has been known for several years, even if the clinical and pathogenetic relevance of this association is not completely defined. This is not a marginal problem since monoclonal gammopathy is present in 1-3% of the population above 50 years in whom it is often asymptomatic, and in at least 8% of patients is associated with a symptomatic neuropathy, representing one of the leading causes of neuropathy in aged people. Monoclonal gammopathy may result from malignant lymphoproliferative diseases including multiple myeloma or solitary plasmocytoma, Waldenström's macroglobulinemia (WM), other IgM-secreting lymphoma or chronic lymphocytic leukemia, and primary systemic amyloidosis (AL). In most instances it is not associated with any of these disorders and is defined monoclonal gammopathy of undetermined significance (MGUS) for its possible, though infrequent, evolution into malignant forms. Several data support the pathogenetic role of the monoclonal gammopathy in the neuropathy particularly when of IgM isotype where IgM reactivity to several neural antigens has been reported. Increased levels of VEGF have been implicated in POEMS syndrome. However, there are as yet no defined therapies for these neuropathies, as their efficacy has not been confirmed in randomized trials.

  14. Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy.

    PubMed

    Zheng, Huaien; Xiao, Wen Hua; Bennett, Gary J

    2011-12-01

    Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicative of a functional impairment and that this results in a chronic axonal energy deficiency that is the cause of the neuropathy's symptoms. However, the significance of mitochondrial swelling and vacuolation is ambiguous and a test of the hypothesis requires a direct assessment of the effects of chemotherapy on mitochondrial function. The results of such an assessment are reported here. Mitochondrial respiration and ATP production were measured in rat sciatic nerve samples taken 1-2 days after and 3-4 weeks after induction of painful peripheral neuropathy with paclitaxel and oxaliplatin. Significant deficits in Complex I-mediated and Complex II-mediated respiration and significant deficits in ATP production were found for both drugs at both time points. In addition, prophylactic treatment with acetyl-l-carnitine, which inhibited the development of paclitaxel-evoked and oxaliplatin-evoked neuropathy, prevented the deficits in mitochondrial function. These results implicate mitotoxicity as a possible cause of chemotherapy-evoked chronic sensory peripheral neuropathy.

  15. Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer

    PubMed Central

    Hernández-Pedro, N.; Fernández-González- Aragón, M.C.; Saavedra-Pérez, D.; Campos-Parra, A.D.; Ríos-Trejo, M.Á.; Cerón-Lizárraga, T.; Martínez-Barrera, L.; Pineda, B.; Ordóñez, G.; Ortiz-Plata, A.; Granados-Soto, V.; Sotelo, J.

    2011-01-01

    Objective: To evaluate the effect of all-trans retinoic acid (ATRA) as treatment for chemotherapy-induced peripheral neuropathy in an experimental animal model and in a randomized, double-blinded, controlled trial in patients with non-small-cell lung cancer (NSCLC). Methods: Forty male Wistar rats were randomized in 5 groups: group A, control; groups B and C, treated with cisplatin; and groups D and E, treated with paclitaxel. ATRA (20 mg/kg PO) was administered for 15 days in groups C and E. We evaluated neuropathy and nerve regeneration–related morphologic changes in sciatic nerve, the concentration of nerve growth factor (NGF), and retinoic acid receptor (RAR)–α and RAR-β expression. In addition, 95 patients with NSCLC under chemotherapy treatment were randomized to either ATRA (20 mg/m2/d) or placebo. Serum NGF, neurophysiologic tests, and clinical neurotoxicity were assessed. Results: The experimental animals developed neuropathy and axonal degeneration, associated with decreased NGF levels in peripheral nerves. Treatment with ATRA reversed sensorial changes and nerve morphology; this was associated with increased NGF levels and RAR-β expression. Patients treated with chemotherapy had clinical neuropathy and axonal loss assessed by neurophysiology, which was related to decreased NGF levels. ATRA reduced axonal degeneration demonstrated by nerve conduction velocity and clinical manifestations of neuropathy grades ≥2. Conclusions: ATRA reduced chemotherapy-induced experimental neuropathy, increased NGF levels, and induced RAR-β expression in nerve. In patients, reduction of NGF in serum was associated with the severity of neuropathy; ATRA treatment reduced the electrophysiologic alterations. Classification of evidence: This study provides Class II evidence that ATRA improves nerve conduction in patients with chemotherapy-induced peripheral neuropathy. Neurology® 2011;77:987–995 PMID:21865574

  16. Thyroid hormone reduces the loss of axotomized sensory neurons in dorsal root ganglia after sciatic nerve transection in adult rat.

    PubMed

    Schenker, Michel; Kraftsik, Rudolf; Glauser, Liliane; Kuntzer, Thierry; Bogousslavsky, Julien; Barakat-Walter, Ibtissam

    2003-11-01

    We have shown that a local administration of thyroid hormones (T3) at the level of transected rat sciatic nerve induced a significant increase in the number of regenerated axons. To address the question of whether local administration of T3 rescues the axotomized sensory neurons from death, in the present study we estimated the total number of surviving neurons per dorsal root ganglion (DRG) in three experimental group animals. Forty-five days following rat sciatic nerve transection, the lumbar (L4 and L5) DRG were removed from PBS-control, T3-treated as well as from unoperated rats, and serial sections (1 microm) were cut. The physical dissector method was used to estimate the total number of sensory neurons in the DRGs. Our results revealed that in PBS-control rats transection of sciatic nerve leads to a significant (P < 0.001) decrease in the mean number of sensory neurons (8743.8 +/- 748.6) compared with the number of neurons in nontransected ganglion (mean 13,293.7 +/- 1368.4). However, administration of T3 immediately after sciatic nerve transection rescues a great number of axotomized neurons so that their mean neuron number (12,045.8 +/- 929.8) is not significantly different from the mean number of neurons in the nontransected ganglion. In addition, the volume of ganglia showed a similar tendency. These results suggest that T3 rescues a high number of axotomized sensory neurons from death and allows these cells to grow new axons. We believe that the relative preservation of neurons is important in considering future therapeutic approaches of human peripheral nerve lesion and sensory neuropathy.

  17. [Peripheral neuropathies: Diagnostic strategy].

    PubMed

    Magy, L

    2017-02-28

    Diagnosing a peripheral neuropathy is sometimes challenging, as the causes are diverse and the clinical pictures heterogeneous. Overall, diagnosing a patient with peripheral neuropathy will require some knowledge in almost every field of medicine. Therefore, it appears crucial to adopt a diagnostic strategy that is based on solid clinical and neurophysiological grounds. The present paper describes a three-step diagnostic strategy: (1) to delineate a clinico-pathologic entity from clinical and electrodiagnostic findings; (2) to propose a list of plausible causes based on step one, history and clinical context; (3) to use appropriate workup in order to determine the cause or mechanism of the neuropathy. The three steps of this diagnostic strategy necessitate a high level of expertise and interaction between physicians is highly desirable. Finally, an aggressive course and a severe impairment should lead to relentlessly look for a curable cause.

  18. Evaluation of ketamine, nimodipine, gabapentin and imipramine in partial sciatic nerve transection model of neuropathic pain in rat: an experimental study.

    PubMed

    Hota, D; Bansal, V; Pattanaik, S

    2007-09-01

    The aim of this research is to study the effects of nimodipine, gabapentin, ketamine and imipramine in the partial sciatic nerve transection (PST) model of neuropathic pain in rats. PST was produced in young Wistar rats of either sex by partial destruction of the sciatic nerve. A decrease in the latency to paw withdrawal reaction on the hot plate was considered as development of neuropathy. The drugs were given daily from the third day of the procedure, and evaluation was done on days 7, 14, 21 and 28. There was a significant decrease (p < 0.05) in the paw withdrawal response in the nimodipine group from day 14 onward when compared with the control group. In the ketamine and imipramine group, this response was seen from day 21 onward. The effect persisted till the end of the study. There was no improvement in the gabapentin group. The results of our study show that nimodipine (dihydropyridine calcium channel blocker), ketamine (NMDA antagonist) and imipramine (tricyclic antidepressant) modulated hyperalgesia and allodynia in the PST model of neuropathy. Gabapentin (an alpha-2 delta calcium subunit blocker) did not show any effect in this model of neuropathy. The widespread use of gabapentin in various types of neuropathic pain thus needs to be reevaluated.

  19. Recurrent brachial plexus neuropathy.

    PubMed

    Bradley, W G; Madrid, R; Thrush, D C; Campbell, M J

    1975-09-01

    The clinical, electrophysiological and pathological changes in 3 patients with recurrent attacks of non-traumatic brachial plexus neuropathy have been described. Two had recurrent attacks and a dominant family history of similar attacks, together with evidence of lesser degrees of nerve involvement outside the brachial plexus. In one patient the attacks were moderately painful, while in the other there was little or no pain. Only one showed undue slowing of motor nerve conduction during ischaemia, but in both cases the sural nerves had the changes of tomaculous neuropathy, with many sausage-shaped swellings of the myelin sheaths, and extensive segmental demyelination and remyelination. The third patient had two attacks of acute brachial plexus neuropathy which were both extremely painful. The clinical features were compatible with a diagnosis of neuralgic amuotrophy. In the second attack, there was vagus nerve involvement and the sural nerve showed evidence of healed extensive segmental demyelination. The various syndromes presenting with acute non-traumatic brachial plexus neuropathy are reviewed, and a tentative nonsological classification advanced. Most patients fall into the category of acute, painful paralysis with amyotrophy, with no family history and no evidence of lesions outside the brachial plexus. It is suggested that the term "neuralgic amyotrophy" be restricted to this group. Patients with features outside this clinical picture probably suffer from other disease entities presenting with brachial plexus neuropathy. The familial cases constitute one or more aetioliogical subgroups, differing from neuralgic amyotrophy in the frequency of recurrences, the relative freedom from pain in the attacks, the frequency of nerve lesions outside the brachial plexus, and of hypotelorism. Individual attacks of acute brachial plexus neuropathy, however, may be identical in patients with the different diseases, and further pathological and biochemical studies are

  20. 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.

  1. Ulnar Neuropathy in Cyclists.

    PubMed

    Brubacher, Jacob W; Leversedge, Fraser J

    2017-02-01

    The form and function of the cyclist exposes the ulnar nerve to both traction and compressive forces at both the elbow and wrist. Prevention of ulnar neuropathy and treatment of early symptoms include bike fitting, avoidance of excessive or prolonged weight-bearing through the hands, and the use of padded gloves. For persisting or progressive symptoms, a thorough history and physical examination is essential to confirm the diagnosis and to rule out other sites of nerve compression. The majority of compression neuropathies in cyclists resolve after appropriate rest and conservative treatment; however, should symptoms persist, nerve decompression may be indicated.

  2. Therapeutic strategies for diabetic neuropathy.

    PubMed

    Habib, Ali A; Brannagan, Thomas H

    2010-03-01

    Diabetes is the leading cause of peripheral neuropathy globally. Duration of diabetes, glycemic control, and preexisting cardiovascular risk factors independently correlate with the development and progression of diabetic peripheral neuropathy as well as cardiovascular autonomic neuropathy. The pathogenesis of diabetic neuropathy remains unclear, although insulin resistance, oxidative stress, mitochondrial dysfunction, abnormal glucose metabolism, advanced glycation end products, neurotrophic factors, and protein kinase C activation all may play a role. Strict glycemic control remains the only available treatment option, although other treatments are in development. Multiple options are available for symptom management. In this article, we review factors associated with development and progression of diabetic neuropathy and discuss available treatment options.

  3. Nerve Wrapping of the Sciatic Nerve With Acellular Dermal Matrix in Chronic Complete Proximal Hamstring Ruptures and Ischial Apophyseal Avulsion Fractures

    PubMed Central

    Haus, Brian M.; Arora, Danny; Upton, Joseph; Micheli, Lyle J.

    2016-01-01

    Background: Patients with chronic injuries of the proximal hamstring can develop significant impairment because of weakness of the hamstring muscles, sciatic nerve compression from scar formation, or myositis ossificans. Purpose: To describe the surgical outcomes of patients with chronic injury of the proximal hamstrings who were treated with hamstring repair and sciatic neurolysis supplemented with nerve wrapping with acellular dermal matrix. Study Design: Retrospective case series; Level of evidence, 4. Methods: Fifteen consecutive patients with a diagnosis of chronic complete proximal hamstring rupture or chronic ischial tuberosity apophyseal avulsion fracture (mean age, 39.67 years; range, 14-69 years) were treated with proximal hamstring repair and sciatic neurolysis supplemented with nerve wrapping with acellular dermal matrix. Nine patients had preoperative sciatica, and 6 did not. Retrospective chart review recorded clinical outcomes measured by the degree of pain relief, the rate of return to activities, and associated postoperative complications. Results: All 15 patients were followed in the postoperative period for an average of 16.6 months. Postoperatively, there were 4 cases of transient sciatic nerve neurapraxia. Four patients (26%) required postoperative betamethasone sodium phosphate (Celestone Soluspan) injectable suspension USP 6 mg/mL. Among the 9 patients with preoperative sciatica, 6 (66%) had a good or excellent outcome and were able to return to their respective activities/sports; 3 (33%) had persistent chronic pain. One of these had persistent sciatic neuropathy that required 2 surgical reexplorations and scar excision after development of recurrent extraneural scar formation. Among the 6 without preoperative sciatica, 100% had a good or excellent outcomes and 83% returned to their respective activities/sports. Better outcomes were observed in younger patients, as the 3 cases of persistent chronic sciatic pain were in patients older than 45

  4. [Pathophysiology of sensory ataxic neuropathy].

    PubMed

    Sobue, G

    1996-12-01

    The main lesions of sensory ataxic neuropathy such as chronic idiopathic sensory ataxic neuropathy, (ISAN), carcinomatous neuropathy, Sjögren syndrome-associated neuropathy and acute autonomic and sensory neuropathy (AASN) are the large-diameter sensory neurons and dosal column of the spinal cord and the large myelinated fibers in the peripheral nerve trunks. In addition, afferent fibers to the Clarke's nuclei are also severely involved, suggesting Ia fibers being involved in these neuropathies. In NT-3 knockout mouse, an animal model of sensory ataxia, large-sized la neurons as well as muscle spindle and Golgi tendon organs are depleted, and are causative for sensory ataxia. Thus, the proprioceptive Ia neurons would play a role in pathogenesis of sensory ataxia in human sensory ataxic neuropathies, but the significance of dorsal column involvement in human sensory ataxia is still needed to evaluate.

  5. Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats

    PubMed Central

    FATANI, AMAL JAMIL; AL-REJAIE, SALIM SALIH; ABUOHASHISH, HATEM MUSTAFA; AL-ASSAF, ABDULLAH; PARMAR, MIHIR YOGESHKUMAR; OLA, MOHAMMAD SHAMSUL; AHMED, MOHAMMED MAHBOOBUDDIN

    2015-01-01

    The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF

  6. Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats.

    PubMed

    Fatani, Amal Jamil; Al-Rejaie, Salim Salih; Abuohashish, Hatem Mustafa; Al-Assaf, Abdullah; Parmar, Mihir Yogeshkumar; Ola, Mohammad Shamsul; Ahmed, Mohammed Mahboobuddin

    2015-05-01

    The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF

  7. EXPERIMENTAL MODEL OF ALCOHOL-RELATED PERIPHERAL NEUROPATHY

    PubMed Central

    MELLION, MICHELLE L.; NGUYEN, VANANH; TONG, MING; GILCHRIST, JAMES; DE LA MONTE, SUZANNE

    2015-01-01

    Introduction The aim of this work was to determine the effect of chronic alcohol exposure on peripheral nerves in a nutritionally balanced rat model of alcoholism. Methods Three different strains of adult male rats were pair-fed for 8 weeks with isocaloric liquid diets containing 0% or 37% ethanol. Nerve conduction studies (NCS) were performed. Peripheral nerve and muscle were examined histologically with morphometrics. Results Ethanol exposure significantly slowed velocity in tibial and fibular nerves, but not in the plantar nerve in all 3 strains. Studies of the sciatic nerve revealed decreased fiber diameters and increased regenerative sprouts in peripheral nerves. There was muscle denervation of ethanol-exposed rats in all 3 strains. Conclusions Chronic ethanol exposure caused a polyneuropathy characterized by axonal degeneration despite adequate nutrition. These results suggest that ethanol exposure has direct neurotoxic effects on peripheral nerves. This model may be useful in understanding the underlying mechanism(s) of alcohol-related peripheral neuropathy. PMID:23761140

  8. Ischemic optic neuropathy.

    PubMed

    Hayreh, Sohan Singh

    2009-01-01

    Ischemic optic neuropathy is one of the major causes of blindness or seriously impaired vision, yet there is disagreement as to its pathogenesis, clinical features and especially its management. This is because ischemic optic neuropathy is not one disease but a spectrum of several different types, each with its own etiology, pathogenesis, clinical features and management. They cannot be lumped together. Ischemic optic neuropathy is primarily of two types: anterior (AION) and posterior (PION), involving the optic nerve head (ONH) and the rest of the optic nerve respectively. Furthermore, both AION and PION have different subtypes. AION comprises arteritic (A-AION - due to giant cell arteritis) and, non-arteritic (NA-AION - due to causes other than giant cell arteritis); NA-AION can be further classified into classical NA-AION and incipient NA-AION. PION consists of arteritic (A-PION - due to giant cell arteritis), non-arteritic (NA-PION - due to causes other than giant cell arteritis), and surgical (a complication of several systemic surgical procedures). Thus, ischemic optic neuropathy consists of six distinct types of clinical entities. NA-AION is by far the most common type and one of the most prevalent and visually crippling diseases in the middle-aged and elderly. A-AION, though less common, is an ocular emergency and requires early diagnosis and immediate treatment with systemic high dose corticosteroids to prevent further visual loss, which is entirely preventable. Controversy exists regarding the pathogenesis, clinical features and especially management of the various types of ischemic optic neuropathy because there are multiple misconceptions about its many fundamental aspects. Recently emerging information on the various factors that influence the optic nerve circulation, and also the various systemic and local risk factors which play important roles in the development of various types of ischemic optic neuropathy have given us a better understanding of

  9. Genetics Home Reference: Leber hereditary optic neuropathy

    MedlinePlus

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

  10. 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

  11. Correlative CT and anatomic study of the sciatic nerve

    SciTech Connect

    Pech, P.; Haughton, V.

    1985-05-01

    Sciatica can be caused by numerous processes affecting the sciatic nerve or its components within the pelvis including tumors, infectious diseases, aneurysms, fractures, and endometriosis. The CT diagnosis of these causes of sciatica has not been emphasized. This study identified the course and appearance of the normal sciatic nerve in the pelvis by correlating CT and anatomic slices in cadavers. For purposes of discussion, the sciatic nerve complex is conveniently divided into three parts: presacral, muscular, and ischial. Each part is illustrated here by two cryosections with corresponding CT images.

  12. Forearm neuropathy and pruritus.

    PubMed

    Massey, E W; Massey, J M

    1986-10-01

    Five adult patients (four of them men) had episodic brachioradial pruritus associated with forearm paresthesia and hypalgesia. No cervical, shoulder, or forearm trauma was known. Onset was variable, but two had had the condition for more than ten years. In each, sensory alteration was detectable by pinprick and temperature in the distribution of the posterior cutaneous nerve of the forearm supplying the skin over the proximal portion of the brachioradial muscle. This seems to be a benign neuropathy.

  13. Metformin attenuates hyperalgesia and allodynia in rats with painful diabetic neuropathy induced by streptozotocin.

    PubMed

    Ma, Junxiong; Yu, Hailong; Liu, Jun; Chen, Yu; Wang, Qi; Xiang, Liangbi

    2015-10-05

    Painful diabetic neuropathy is a common complication of diabetes mellitus, which often makes the patients suffer from severe hyperalgesia and allodynia. Thus far, the treatment of painful diabetic neuropathy remains unsatisfactory. Metformin, which is the first-line drug for type-2 diabetes, has been proved to attenuate hyperexcitability in sensory neurons linked to chemotherapy-induced neuropathic pain, highlighting its potential in alleviating pain related with painful diabetic neuropathy. The present study was designed to investigate the potential beneficial effect of metformin on hyperalgesia and allodynia in diabetic rats. The mechanical sensitivity, heat nociception, and cold allodynia were examined. The levels of malondialdehyde, superoxide dismutase, and advanced glycation end-products in the blood were measured. The expression of adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and AMPK target genes were examined in the sciatic nerves of the animals. It was found that metformin was capable of attenuating diabetes-induced mechanical hyperalgesia, heat hyperalgesia and cold allodynia. In addition, metformin was capable of decreasing malondialdehyde and glycation end-products levels in blood, as well as increasing superoxide dismutas activity, indicating the inhibitory effect of metformin against diabetes-induced oxidative stress. Further studies showed that metformin could activate AMPK and increase the AMPK target genes in sciatic nerves in diabetic rats. In conclusion, metformin is able to attenuate diabetes-induced hyperalgesia and allodynia, which might be associated its anti-oxidative effect through AMPK pathway. Metformin might be used as an effective drug, especially with fewer side effects, for abnormal sensation in painful diabetic neuropathy.

  14. Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection.

    PubMed

    Chacur, M; Matos, R J B; Alves, A S; Rodrigues, A C; Gutierrez, V; Cury, Y; Britto, L R G

    2010-04-01

    Nerve injury leads to a neuropathic pain state that results from central sensitization. This phenomenom is mediated by NMDA receptors and may involve the production of nitric oxide (NO). In this study, we investigated the expression of the neuronal isoform of NO synthase (nNOS) in the spinal cord of 3-month-old male, Wistar rats after sciatic nerve transection (SNT). Our attention was focused on the dorsal part of L3-L5 segments receiving sensory inputs from the sciatic nerve. SNT resulted in the development of neuropathic pain symptoms confirmed by evaluating mechanical hyperalgesia (Randall and Selitto test) and allodynia (von Frey hair test). Control animals did not present any alteration (sham-animals). The selective inhibitor of nNOS, 7-nitroindazole (0.2 and 2 microg in 50 microL), blocked hyperalgesia and allodynia induced by SNT. Immunohistochemical analysis showed that nNOS was increased (48% by day 30) in the lumbar spinal cord after SNT. This increase was observed near the central canal (Rexed's lamina X) and also in lamina I-IV of the dorsal horn. Real-time PCR results indicated an increase of nNOS mRNA detected from 1 to 30 days after SNT, with the highest increase observed 1 day after injury (1469%). Immunoblotting confirmed the increase of nNOS in the spinal cord between 1 and 15 days post-lesion (20%), reaching the greatest increase (60%) 30 days after surgery. The present findings demonstrate an increase of nNOS after peripheral nerve injury that may contribute to the increase of NO production observed after peripheral neuropathy.

  15. Management of painful neuropathies.

    PubMed

    Brix Finnerup, Nanna; Hein Sindrup, Søren; Staehelin Jensen, Troels

    2013-01-01

    Neuropathic pain is the most common type of pain in neuropathy. In painful polyneuropathies the pain usually has a "glove and stocking" distribution. The pain may be predominantly spontaneous, e.g., with a burning, pricking, or shooting character or characterized by evoked pain such as mechanical or cold allodynia. In the clinical setting, the prevention of painful neuropathies and treatment of underlying neuropathy remains inadequate and thus symptomatic treatment of the pain and related disability needs to be offered. Most randomized, double-blind, placebo-controlled trials (RCTs) published in painful neuropathy have been conducted in patients with diabetes and to what extent a treatment which is found effective in painful diabetic polyneuropathy can be expected to relieve other conditions like chemotherapy- or HIV-induced neuropathy is unknown. Tricyclic antidepressants (TCAs), gabapentin, pregabalin, and serotonin noradrenaline reuptake inhibitors (SNRIs) are first drug choices. In patients with localized neuropathic pain, a topical lidocaine patch may also be considered. Second-line treatments are tramadol and other opioids. New types of treatment include botulinum toxin type A (BTX-A), high-dose capsaicin patches, and cannabinoids. Other types of anticonvulsant drugs such as lamotrigine, oxcarbazepine, and lacosamide have a more questionable efficacy in painful polyneuropathy but may have an effect in a subgroup of patients. Combination therapy may be considered in patients with insufficient effect from one drug. Treatment is usually a trial-and-error process and has to be individualized to the single patient, taking into account all comorbidities such as possible concomitant depression, anxiety, diseases, and drug interactions. Side-effects to antidepressants include dry mouth, nausea, constipation, orthostatic hypotension, and sedation. ECG should always be obtained prior to treatment with TCAs, which also should not be used in patients with cardiac

  16. A prospective study of acute idiopathic neuropathy. III. Immunological studies.

    PubMed Central

    Winer, J B; Gray, I A; Gregson, N A; Hughes, R A; Leibowitz, S; Shepherd, P; Taylor, W A; Yewdall, V

    1988-01-01

    The immune responses of 100 patients who presented with an acute idiopathic neuropathy were compared with those of age and sex matched controls. Blood lymphocytes and their subsets were counted with a fluorescent activated cell sorter. CD8+ (putative suppressor) lymphocytes were significantly reduced in the first week of the disease but total lymphocytes, total T and CD4+ (putative helper) cells were not altered. This reduction depended on the nature of the preceding infection. Serum complement C3 and C4 concentrations remained normal and immune complexes were rarely detected with a C1q binding assay. Complement-fixing antibodies to human peripheral nerve antigens were discovered in the serum of 7% of patients but only 1% of controls. Complement-fixing antibodies to galactocerebroside were not discovered in any sera. Enzyme-linked immunoassays detected increased antibody responses to galactocerebroside but none at all to human P2 myelin protein in the patient sera. Forty microliter of serum from five patients injected into the sciatic nerves of rats did not induce significantly more demyelination than the serum from control patients. It is concluded that auto-immune responses can only be detected by these techniques in a small minority of patients with acute idiopathic neuropathy. PMID:2969956

  17. Late sciatic nerve axonotmesis following acetabular reconstruction plate.

    PubMed

    Moreta, J; Foruria, X; Labayru, F

    2016-01-01

    Sciatic nerve injuries associated with acetabular fractures can be post-traumatic, perioperative or postoperative. Late postoperative injury is very uncommon and can be due to heterotopic ossifications, muscular scarring, or implant migration. A case is presented of a patient with a previous transverse acetabular fracture treated with a reconstruction plate for the posterior column. After 17 years, she presented with progressive pain and motor deficit in the sciatic territory. Radiological and neurophysiological assessments were performed and the patient underwent surgical decompression of the sciatic nerve. A transection of the nerve was observed that was due to extended compression of one of the screws. At 4 years postoperatively, her pain had substantially diminished and the paresthesias in her leg had resolved. However, her motor symptoms did not improve. This case report could be relevant due to this uncommon delayed sciatic nerve injury due to prolonged hardware impingement.

  18. Ursolic acid induces neural regeneration after sciatic nerve injury

    PubMed Central

    Liu, Biao; Liu, Yan; Yang, Guang; Xu, Zemin; Chen, Jiajun

    2013-01-01

    In this study, we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve. BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis at 0.5 cm below the ischial tube-rosity. The successfully generated model mice were treated with 10, 5, or 2.5 mg/kg ursolic acid via intraperitoneal injection. Enzyme-linked immunosorbent assay results showed that serum S100 protein expression level gradually increased at 1–4 weeks after sciatic nerve injury, and significantly decreased at 8 weeks. As such, ursolic acid has the capacity to significantly increase S100 protein expression levels. Real-time quantitative PCR showed that S100 mRNA expression in the L4–6 segments on the injury side was increased after ursolic acid treatment. In addition, the muscular mass index in the soleus muscle was also increased in mice treated with ursolic acid. Toluidine blue staining revealed that the quantity and average diameter of myelinated nerve fibers in the injured sciatic nerve were significantly increased after treatment with ursolic acid. 10 and 5 mg/kg of ursolic acid produced stronger effects than 2.5 mg/kg of ursolic acid. Our findings indicate that ursolic acid can dose-dependently increase S100 expression and promote neural regeneration in BALB/c mice following sciatic nerve injury. PMID:25206561

  19. Biodegradable magnesium wire promotes regeneration of compressed sciatic nerves

    PubMed Central

    Li, Bo-han; Yang, Ke; Wang, Xiao

    2016-01-01

    Magnesium (Mg) wire has been shown to be biodegradable and have anti-inflammatory properties. It can induce Schwann cells to secrete nerve growth factor and promote the regeneration of nerve axons after central nervous system injury. We hypothesized that biodegradable Mg wire may enhance compressed peripheral nerve regeneration. A rat acute sciatic nerve compression model was made, and AZ31 Mg wire (3 mm diameter; 8 mm length) bridged at both ends of the nerve. Our results demonstrate that sciatic functional index, nerve growth factor, p75 neurotrophin receptor, and tyrosine receptor kinase A mRNA expression are increased by Mg wire in Mg model. The numbers of cross section nerve fibers and regenerating axons were also increased. Sciatic nerve function was improved and the myelinated axon number was increased in injured sciatic nerve following Mg treatment. Immunofluorescence histopathology showed that there were increased vigorous axonal regeneration and myelin sheath coverage in injured sciatic nerve after Mg treatment. Our findings confirm that biodegradable Mg wire can promote the regeneration of acute compressed sciatic nerves. PMID:28197200

  20. Biodegradable magnesium wire promotes regeneration of compressed sciatic nerves.

    PubMed

    Li, Bo-Han; Yang, Ke; Wang, Xiao

    2016-12-01

    Magnesium (Mg) wire has been shown to be biodegradable and have anti-inflammatory properties. It can induce Schwann cells to secrete nerve growth factor and promote the regeneration of nerve axons after central nervous system injury. We hypothesized that biodegradable Mg wire may enhance compressed peripheral nerve regeneration. A rat acute sciatic nerve compression model was made, and AZ31 Mg wire (3 mm diameter; 8 mm length) bridged at both ends of the nerve. Our results demonstrate that sciatic functional index, nerve growth factor, p75 neurotrophin receptor, and tyrosine receptor kinase A mRNA expression are increased by Mg wire in Mg model. The numbers of cross section nerve fibers and regenerating axons were also increased. Sciatic nerve function was improved and the myelinated axon number was increased in injured sciatic nerve following Mg treatment. Immunofluorescence histopathology showed that there were increased vigorous axonal regeneration and myelin sheath coverage in injured sciatic nerve after Mg treatment. Our findings confirm that biodegradable Mg wire can promote the regeneration of acute compressed sciatic nerves.

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

    PubMed

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

    2011-08-01

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

  2. Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury.

    PubMed

    Villalón, Eric; Dale, Jeffrey M; Jones, Maria; Shen, Hailian; Garcia, Michael L

    2015-11-19

    Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L(E397K), which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L(E397K) mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K). Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L(E397K) mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K) mice provide a model for determining the efficacy of novel therapies.

  3. Fisetin Imparts Neuroprotection in Experimental Diabetic Neuropathy by Modulating Nrf2 and NF-κB Pathways.

    PubMed

    Sandireddy, Reddemma; Yerra, Veera Ganesh; Komirishetti, Prashanth; Areti, Aparna; Kumar, Ashutosh

    2016-08-01

    The current study is aimed to assess the therapeutic potential of fisetin, a phytoflavonoid in streptozotocin (STZ)-induced experimental diabetic neuropathy (DN) in rats. Fisetin was administered (5 and 10 mg/kg) for 2 weeks (7th and 8th week) post STZ administration. Thermal and mechanical hyperalgesia were assessed by measuring tactile sensitivity to thermal and mechanical stimuli, respectively. Motor nerve conduction velocity (MNCV) was determined using power lab system and sciatic nerve blood flow (NBF) was determined using laser Doppler system. Nerve sections were processed for TUNEL assay and NF-κB, COX-2 immunohistochemical staining. Sciatic nerve homogenate was used for biochemical and Western blotting analysis. MNCV and sciatic NBF deficits associated with DN were ameliorated in fisetin administered rats. Fisetin treatment reduced the interleukin-6 and tumour necrosis factor-alpha in sciatic nerves of diabetic rats (p < 0.001). Protein expression studies have identified that the therapeutic benefit of fisetin might be through regulation of redox sensitive transcription factors such as nuclear erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB). Our study provides an evidence for the therapeutic potential of fisetin in DN through simultaneous targeting of NF-κB and Nrf2.

  4. Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

    NASA Astrophysics Data System (ADS)

    Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernández, María G. H.; Jasso, José L. C.; Lira, Maricela O. F.; Flores, Mariana A.; Balderrama, Vicente L.

    2010-05-01

    The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours and at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p<0.001 and p<000) as in the amplitude (p<000 and p<000). Groups 3 and 4, which was stimulated at 100 mA and 100 ms latency showed no statistically significant difference (p>000), as to the extent, if any statistically significant difference. (p<0.001 and p<0.000). The laser produces a favorable response in the treatment of paresthesia (post-traumatic neuropathy).

  5. Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

    SciTech Connect

    Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernandez, Maria G. H.; Jasso, Jose L. C.

    2010-05-31

    The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours and at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p<0.001 and p<000) as in the amplitude (p<000 and p<000). Groups 3 and 4, which was stimulated at 100 mA and 100 ms latency showed no statistically significant difference (p>000), as to the extent, if any statistically significant difference. (p<0.001 and p<0.000). The laser produces a favorable response in the treatment of paresthesia (post-traumatic neuropathy).

  6. The effects of free fat grafts on the stiffness of the rat sciatic nerve and perineural scar.

    PubMed

    Dumanian, G A; McClinton, M A; Brushart, T M

    1999-01-01

    We developed a new quantitative rat sciatic nerve model to test whether free fat grafts can reduce postoperative perineural scar formation. Epineurectomies of sciatic nerves were performed to create scar. The force required to distract the nerve a unit distance was measured after surgery to determine the time of maximal scar formation. Nerve stiffness normalized for rat weight was statistically greater at 2 months after the initial dissection (0.097+/-0.009 g/mm/g rat weight; n = 10 limbs) than rat limbs that had not undergone a previous dissection (0.075+/-0.012 g/mm/g rat weight). Perineural scar thickness was thicker at 2 months than the perineural tissue in preoperative controls. Free fat grafts decreased nerve stiffness at 2 months (0.078+/-0.012 g/mm/g rat weight) in comparison to the contralateral surgical control limb without a fat graft (0.094+/-0.014 g/mm/g rat weight). Free fat grafts reduced the strength of postoperative perineural scar in this surgical model; however, they were associated with an unexpected finding of substantial postoperative neuropathy.

  7. [Surgical therapy for entrapment neuropathy].

    PubMed

    Tachibana, Shigekuni

    2012-01-01

    Entrapment neuropathy is not uncommon, and surgical treatment is followed by favorite result. Therefore, to obtain an accurate diagnosis based on precise knowledge of the peripheral nervous system is very important. The most popular and useful symptoms and signs of the entrapment neuropathy is paresthesia, dysesthesia and Tinel's like sign at the lesion site. Nerve conduction study is also valuable for the accurate diagnosis. For the last 30 years, the author operated on 1,399 lesions of entrapment neuropathy. They consist of 877 carpal tunnel syndrome (63%), 284 tarsal tunnel syndrome (20%), 135 ulnar neuropathy at the elbow (10%), 53 piriformis syndrome (4%), 15 thoracic outlet syndrome (1%), and others. From the pathophysiological point to view, except for the carpal tunnel syndrome, several locations and factors come into play producing the entrapment of the nerve. The author would like to stress that the entrapment neuropathy is not severe disease, though, it strongly insult the patient's quality of life.

  8. Dysfunction of nodes of Ranvier: a mechanism for anti-ganglioside antibody-mediated neuropathies

    PubMed Central

    Susuki, Keiichiro; Yuki, Nobuhiro; Schafer, Dorothy P.; Hirata, Koichi; Zhang, Gang; Funakoshi, Kei; Rasband, Matthew N.

    2011-01-01

    Autoantibodies against gangliosides GM1 or GD1a are associated with acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN), whereas antibodies to GD1b ganglioside are detected in acute sensory ataxic neuropathy (ASAN). These neuropathies have been proposed to be closely related and comprise a continuous spectrum, although the underlying mechanisms, especially for sensory nerve involvement, are still unclear. Antibodies to GM1 and GD1a have been proposed to disrupt the nodes of Ranvier in motor nerves via complement pathway. We hypothesized that the disruption of nodes of Ranvier is a common mechanism whereby various anti-ganglioside antibodies found in these neuropathies lead to nervous system dysfunction. Here, we show that the IgG monoclonal anti-GD1a/GT1b antibody injected into rat sciatic nerves caused deposition of IgG and complement products on the nodal axolemma and disrupted clusters of nodal and paranodal molecules predominantly in motor nerves, and induced early reversible motor nerve conduction block. Injection of IgG monoclonal anti-GD1b antibody induced nodal disruption predominantly in sensory nerves. In an ASAN rabbit model associated with IgG anti-GD1b antibodies, complement-mediated nodal disruption was observed predominantly in sensory nerves. In an AMAN rabbit model associated with IgG anti-GM1 antibodies, complement attack of nodes was found primarily in motor nerves, but occasionally in sensory nerves as well. Periaxonal macrophages and axonal degeneration were observed in dorsal roots from ASAN rabbits and AMAN rabbits. Thus, nodal disruption may be a common mechanism in immune-mediated neuropathies associated with autoantibodies to gangliosides GM1, GD1a, or GD1b, providing an explanation for the continuous spectrum of AMAN, AMSAN, and ASAN. PMID:22178332

  9. Painful neuropathy: Mechanisms.

    PubMed

    Lee-Kubli, Corinne A; Calcutt, Nigel A

    2014-01-01

    Painful neuropathy, like the other complications of diabetes, is a growing healthcare concern. Unfortunately, current treatments are of variable efficacy and do not target underlying pathogenic mechanisms, in part because these mechanisms are not well defined. Rat and mouse models of type 1 diabetes are frequently used to study diabetic neuropathy, with rats in particular being consistently reported to show allodynia and hyperalgesia. Models of type 2 diabetes are being used with increasing frequency, but the current literature on the progression of indices of neuropathic pain is variable and relatively few therapeutics have yet been developed in these models. While evidence for spontaneous pain in rodent models is sparse, measures of evoked mechanical, thermal and chemical pain can provide insight into the pathogenesis of the condition. The stocking and glove distribution of pain tantalizingly suggests that the generator site of neuropathic pain is found within the peripheral nervous system. However, emerging evidence demonstrates that amplification in the spinal cord, via spinal disinhibition and neuroinflammation, and also in the brain, via enhanced thalamic activity or decreased cortical inhibition, likely contribute to the pathogenesis of painful diabetic neuropathy. Several potential therapeutic strategies have emerged from preclinical studies, including prophylactic treatments that intervene against underlying mechanisms of disease, treatments that prevent gains of nociceptive function, treatments that suppress enhancements of nociceptive function, and treatments that impede normal nociceptive mechanisms. Ongoing challenges include unraveling the complexity of underlying pathogenic mechanisms, addressing the potential disconnect between the perceived location of pain and the actual pain generator and amplifier sites, and finding ways to identify which mechanisms operate in specific patients to allow rational and individualized choice of targeted therapies.

  10. Subacute diabetic proximal neuropathy

    NASA Technical Reports Server (NTRS)

    Pascoe, M. K.; Low, P. A.; Windebank, A. J.; Litchy, W. J.

    1997-01-01

    OBJECTIVE: To evaluate the clinical, electrophysiologic, autonomic, and neuropathologic characteristics and the natural history of subacute diabetic proximal neuropathy and its response to immunotherapy. MATERIAL AND METHODS: For the 12-year period from 1983 to 1995, we conducted a retrospective review of medical records of Mayo Clinic patients with diabetes who had subacute onset and progression of proximal weakness. The responses of treated versus untreated patients were compared statistically. RESULTS: During the designated study period, 44 patients with subacute diabetic proximal neuropathy were encountered. Most patients were middle-aged or elderly, and no sex preponderance was noted. The proximal muscle weakness often was associated with reduced or absent lower extremity reflexes. Associated weight loss was a common finding. Frequently, patients had some evidence of demyelination on nerve conduction studies, but it invariably was accompanied by concomitant axonal degeneration. The cerebrospinal fluid protein concentration was usually increased. Diffuse and substantial autonomic failure was generally present. In most cases, a sural nerve biopsy specimen suggested demyelination, although evidence of an inflammatory infiltrate was less common. Of 12 patients who received treatment (with prednisone, intravenous immune globulin, or plasma exchange), 9 had improvement of their conditions, but 17 of 29 untreated patients (59%) with follow-up also eventually had improvement, albeit at a much slower rate. Improvement was usually incomplete. CONCLUSION: We suggest that the entity of subacute diabetic proximal neuropathy is an extensive and severe variant of bilateral lumbosacral radiculoplexopathy, with some features suggestive of an immune-mediated cause. It differs from chronic inflammatory demyelinating polyradiculoneuropathy in that most cases have a more restricted distribution and seem to be monophasic and self-limiting. The efficacy of immunotherapy is unproved

  11. 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

  12. Anti-allodynic and neuroprotective effects of koumine, a Benth alkaloid, in a rat model of diabetic neuropathy.

    PubMed

    Ling, Qian; Liu, Ming; Wu, Min-Xia; Xu, Ying; Yang, Jian; Huang, Hui-Hui; Yu, Chang-Xi

    2014-01-01

    Diabetic neuropathy is characterized by progressive degeneration of nerve fibers associated with diabetes mellitus. Antidepressants and anticonvulsants are the mainstay of pharmacological treatment, but are often limited in effectiveness against the core clinical feature of pain. In the current study, we examined the potential effects of koumine, a Gelsemium elegans Benth alkaloid, using a rat model of diabetic neuropathy. Rats were administered intraperitoneally a single dose of streptozocin (60 mg/kg) to induce type 1 diabetes. Koumine was given at a dose range of 0.056-7 mg/kg subcutaneously for one week starting 3 weeks after streptozocin adminstration. Behavioral responses to mechanical stimuli were evaluated every day after streptozocin injection. At 4 weeks after streptozocin injection, sensory nerve conduction velocity (SNCV) and morphological alternation of sciatic nerves were assessed by electron microscopy. Diabetic rats developed mechanical hyperalgesia within 3 weeks after streptozocin injection and exhibited reduced SNCV and impaired myelin/axonal structure. Koumine treatment of diabetic rats decreased neuropathic pain behavior as early as after the first administration. At a dose of 7 mg/kg, koumine was more effective than gabapentin (100 mg/kg), and decreased mechanical sensitivity threshold to a level comparable to healthy control. Repeated treatment of koumine significantly reduced the damage to axon and myelin sheath of the sciatic nerve and increased SNCV, without affecting body weight and blood glucose. These findings encourage the use of koumine in the treatment of diabetic neuropathy.

  13. Evaluation of PMI-5011, an ethanolic extract of Artemisia dracunculus L., on peripheral neuropathy in streptozotocin-diabetic mice

    PubMed Central

    WATCHO, PIERRE; STAVNIICHUK, ROMAN; TANE, PIERRE; SHEVALYE, HANNA; MAKSIMCHYK, YURY; PACHER, PAL; OBROSOVA, IRINA G.

    2011-01-01

    We previously reported that PMI-5011, an ethanolic extract of Artemisia dracunculus L., alleviates peripheral neuropathy in high fat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and pro-inflammatory changes in the peripheral nervous system. This study evaluated PMI-5011 on established functional, structural, and biochemical changes associated with Type I diabetic peripheral neuropathy. C57BL6/J mice with streptozotocin-induced diabetes of a 12-week duration, developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia, and intra-epidermal nerve fiber loss. PMI-5011 (500 mg/kg/day for 7 weeks) alleviated diabetes-induced nerve conduction slowing, small sensory nerve fiber dysfunction, and increased intra-epidermal nerve fiber density. PMI-5011 blunted sciatic nerve and spinal cord 12/15-lipoxygenase activation and oxidative-nitrosative stress, without ameliorating hyperglycemia or reducing sciatic nerve sorbitol pathway intermediate accumulation. In conclusion, PMI-5011, a safe and non-toxic botanical extract, may find use in the treatment of diabetic peripheral neuropathy. PMID:21225225

  14. Concurrent targeting of nitrosative stress-PARP pathway corrects functional, behavioral and biochemical deficits in experimental diabetic neuropathy

    SciTech Connect

    Negi, Geeta; Kumar, Ashutosh; Sharma, Shyam S.

    2010-01-01

    Peroxynitrite mediated nitrosative stress, an indisputable initiator of DNA damage and overactivation of poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated after sensing DNA damage, are two crucial pathogenetic mechanisms in diabetic neuropathy. The intent of the present study was to investigate the effect of combination of a peroxynitrite decomposition catalyst (PDC), FeTMPyP and a PARP inhibitor, 4-ANI against diabetic peripheral neuropathy. The end points of evaluation of the study included motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) for evaluating nerve functions; thermal hyperalgesia and mechanical allodynia for assessing nociceptive alterations, malondialdehyde and peroxynitrite levels to detect oxidative stress-nitrosative stress; NAD concentration in sciatic nerve to assess overactivation of PARP. Additionally immunohistochemical studies for nitrotyrosine and Poly(ADP-ribose) (PAR) was also performed. Treatment with the combination of FeTMPyP and 4-ANI led to significant improvement in nerve functions and pain parameters and also attenuated the oxidative-nitrosative stress markers. Further, the combination also reduced the overactivation of PARP as evident from increased NAD levels and decreased PAR immunopositivity in sciatic nerve microsections. Thus, it can be concluded that treatment with the combination of a PDC and PARP inhibitor attenuates alteration in peripheral nerves in diabetic neuropathy (DN).

  15. Gender-specific differences in diabetic neuropathy in BTBR ob/ob mice

    PubMed Central

    O’Brien, Phillipe D.; Hur, Junguk; Robell, Nicholas J.; Hayes, John M.; Sakowski, Stacey A.; Feldman, Eva L.

    2015-01-01

    Aims To identify a female mouse model of diabetic peripheral neuropathy (DPN), we characterized DPN in female BTBR ob/ob mice and compared their phenotype to non-diabetic and gender-matched controls. We also identified dysregulated genes and pathways in sciatic nerve (SCN) and dorsal root ganglia (DRG) of female BTBR ob/ob mice to determine potential DPN mechanisms. Methods Terminal neuropathy phenotyping consisted of examining latency to heat stimuli, sciatic motor and sural sensory nerve conduction velocities (NCV), and intraepidermal nerve fiber (IENF) density. For gene expression profiling, DRG and SCN were dissected, RNA was isolated and processed using microarray technology and differentially expressed genes were identified. Results Similar motor and sensory NCV deficits were observed in male and female BTBR ob/ob mice at study termination; however, IENF density was greater in female ob/ob mice than their male counterparts. Male and female ob/ob mice exhibited similar weight gain, hyperglycemia, and hyperinsulinemia compared to non-diabetic controls, although triglycerides were elevated more so in males than in females. Transcriptional profiling of nerve tissue from female mice identified dysregulation of pathways related to inflammation. Conclusions Similar to males, female BTBR ob/ob mice display robust DPN, and pathways related to inflammation are dysregulated in peripheral nerve. PMID:26525588

  16. The neuroprotective effects of progesterone on experimental diabetic neuropathy in rats.

    PubMed

    Sameni, H R; Panahi, M; Sarkaki, A; Saki, G H; Makvandi, M

    2008-08-15

    This study was conducted to investigate the neuroprotective effects of progesterone (PROG) on electrophysiological and histomorphometrical alternation in STZ-induced diabetic neuropathy starting from 4 weeks after the diabetic induction. Thirty adult male Sprague-Dawley rats were randomly divided into 3 groups (with 10 rats in each), control (nondiabetic), untreated diabetic and diabetic PROG-treated. Diabetes was induced in adult male rats by a single dose injection of streptozotocin (STZ, 55 mg kg(-1), i.p.). In the PROG-treated group, 4 weeks after induce of diabetes; rats were treated with PROG (8 mg kg(-1), i.p., every two days) for 6 weeks. Diabetic rats showed a significant reduction in motor nerve conduction velocity (MNCV), mean myelinated fibers (MFs) diameter, axon diameter and myelin sheath thickness in the sciatic nerve after 6 weeks. In the untreated diabetic group endoneurial edema was observed in sciatic nerve and the numbers of MFs with infolding into the axoplasm, irregularity of fibers, myelin sheath with unclear boundaries and alteration in myelin compaction were also increased. Long-term treatment with PROG increased MNCV significantly and prevented all these abnormalities in treated diabetic rats. Our findings indicated that PROG as a therapeutic approach can protect neurophysiologic and histomorphologic alterations induced by peripheral diabetic neuropathy.

  17. Effects of Alcohol Injection in Rat Sciatic Nerve

    PubMed Central

    Mazoch, Mathew J.; Cheema, Gulraiz A.; Suva, Larry J.; Thomas, Ruth L.

    2015-01-01

    Background Previous studies have shown that the injection of dehydrated alcohol has been successful for the treatment of Morton's neuroma in the foot. In this study, we determined the cellular effect of injection of alcohol into and around the sciatic nerve of rats, and measured the extent of cell necrosis and/or any associated histologic or inflammatory changes. Methods Twenty-two male (~375g) Wistar rats were randomized into two groups each receiving alcohol injections into or around the sciatic nerve after nerve exposure under sterile technique. Group 1 rats were injected with a 0.5ml solution of 0.5% Marcaine in the left sciatic nerve as a control group. In the right sciatic nerve a 0.5ml solution of 4% ethanol with 0.5% Marcaine was injected. Group 2 rats received 0.5ml of 20%ethanol with 0.5% Marcaine injected into the left sciatic nerve and 0.5 ml of 30% ethanol with 0.5% Marcaine injected into the right sciatic nerve. In each group, the rats were placed in 3 subgroups: intraneural, perineural, perimuscular injections. All rats were sacrificed and tissue harvested for histologic evaluation at day 10 post injection. Results No evidence of alcohol-associated cell necrosis, apoptosis or apparent inflammation was observed in histologic specimens of any injected nerves, perineural tissue, or muscles in controls or experimental groups regardless of concentration of ethanol injected on day 10. Conclusion We concluded that alcohol injection (≤30% ethanol) into and/or around the sciatic nerve or the adjacent muscle of rats has no histologic evidence of necrosis or inflammation to the nerve or surrounding tissue. There was no observable histological change in apoptosis, or cell number, in response to the alcohol injection. PMID:25097192

  18. Metabolic neuropathies and myopathies.

    PubMed

    D'Amico, Adele; Bertini, Enrico

    2013-01-01

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

  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. 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

  1. Immunotherapy of idiopathic inflammatory neuropathies.

    PubMed

    Donofrio, Peter D

    2003-09-01

    Evaluation of peripheral neuropathy is a common reason for referral to a neurologist. Recent advances in immunology have identified an inflammatory component in many neuropathies and have led to treatment trials using agents that attenuate this response. This article reviews the clinical presentation and treatment of the most common subacute inflammatory neuropathies, Guillain-Barré syndrome (GBS) and Fisher syndrome, and describes the lack of response to corticosteroids and the efficacy of treatment with plasma exchange and intravenous immunoglobulin (IVIG). Chronic inflammatory demyelinating polyneuropathy, although sharing some clinical, electrodiagnostic, and pathologic similarities to GBS, improves after treatment with plasma exchange and IVIG and numerous immunomodulatory agents. Controlled trials in multifocal motor neuropathy have shown benefit after treatment with IVIG and cyclophosphamide. Also discussed is the treatment of less common inflammatory neuropathies whose pathophysiology involves monoclonal proteins or antibodies directed against myelin-associated glycoprotein or sulfatide. Little treatment data exist to direct the clinician to proper management of rare inflammatory neuropathies resulting from osteosclerotic myeloma; POEMS syndrome; vasculitis; Sjögren's syndrome; and neoplasia (paraneoplastic neuropathy).

  2. Perineural dexmedetomidine effects on sciatic nerve in rat.

    PubMed

    Yektaş, Abdulkadir; Çabalar, Murat; Sar, Mehmet; Alagöl, Ayşin; Çelik, Duygu Sultan; Yayla, Vildan; Tolga, Deniz

    The present study was designed to test the hypothesis that high dose dexmedetomidine would increase the duration of antinociception to a thermal stimulus in a rat model of sciatic nerve blockade without causing nerve damage. The rats were anesthetized with isoflurane. After electromyography (EMG) recordings, right sciatic nerves were explored and perineural injections were delivered: Group D (n=7), 40μgμgkg(-1) dexmedetomidine administration, Group II (n=6), (0.2mL) saline administration, Group III (n=2), only surgically exploration of the right sciatic nevre. Time to paw withdrawal latency (PAW) to a thermal stimulus for both paws and an assessment of motor function were measured every 30min after the nerve block until a return to baseline. The compound muscle action potential (CMAP) of right and left sciatic nerves were recorded 10 times per each nerve once more after perineural injections at 14 day. After EMG recordings, right and the part of left sciatic nerve were excised at a length of at minimum 15mm for histopathological examination. Comparison of right/left CMAP amplitude ratios before and 14 days after the procedure showed a statistically significant difference (p=0.000). There were no differences in perineural inflammation between the Group D, Group S, and Group E at 14 days.

  3. [Perineural dexmedetomidine effects on sciatic nerve in rat].

    PubMed

    Yektaş, Abdulkadir; Çabalar, Murat; Sar, Mehmet; Alagöl, Ayşin; Çelik, Duygu Sultan; Yayla, Vildan; Tolga, Deniz

    The present study was designed to test the hypothesis that high dose dexmedetomidine would increase the duration of antinociception to a thermal stimulus in a rat model of sciatic nerve blockade without causing nerve damage. The rats were anesthetized with isoflurane. After electromyography (EMG) recordings, right sciatic nerves were explored and perineural injections were delivered: Group D (n=7), 40μgμgkg(-1) dexmedetomidine administration, Group II (n=6), (0.2mL) saline administration, Group III (n=2), only surgically exploration of the right sciatic nevre. Time to paw withdrawal latency (PAW) to a thermal stimulus for both paws and an assessment of motor function were measured every 30min after the nerve block until a return to baseline. The compound muscle action potential (CMAP) of right and left sciatic nerves were recorded 10 times per each nerve once more after perineural injections at 14 day. After EMG recordings, right and the part of left sciatic nerve were excised at a length of at minimum 15mm for histopathological examination. Comparison of right/left CMAP amplitude ratios before and 14 days after the procedure showed a statistically significant difference (p=0.000). There were no differences in perineural inflammation between the Group D, Group S, and Group E at 14 days.

  4. 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.

  5. Intraneural dexamethasone applied simultaneously to rat sciatic nerve constriction delays the development of hyperalgesia and allodynia.

    PubMed

    Bastos, Leandro F S; Medeiros, Daniel C; Vieira, Rafael P; Watkins, Linda R; Coelho, Márcio M; Moraes, Márcio F D

    2012-02-21

    Although neuroimmune interactions associated with the development of pain sensitization in models of neuropathic pain have been widely studied, there are some aspects that require further investigation. Thus, we aimed to evaluate whether the local intraneural or perineural injections of dexamethasone, an efficacious anti-inflammatory and immunosuppressant drug, delays the development of both thermal hyperalgesia and mechanical allodynia in an experimental model of neuropathic pain in rats. Hargreaves and electronic von Frey tests were applied. The chronic constriction injury (CCI) of right sciatic nerve was performed. Single intraneural dexamethasone administration at the moment of constriction delayed the development of sensitization for thermal hyperalgesia and mechanical allodynia. However, perineural administration of dexamethasone, at the highest dose, did not delay experimental pain development. These results show that inflammation/immune response at the site of nerve lesion is an essential trigger for the pathological changes that lead to both hyperalgesia and allodynia. In conclusion, this approach opens new opportunities to study cellular and molecular neuroimmune interactions associated with the development of pain derived from peripheral neuropathies.

  6. Altered protein phosphorylation in sciatic nerve from rats with streptozocin-induced diabetes

    SciTech Connect

    Schrama, L.H.; Berti-Mattera, L.N.; Eichberg, J.

    1987-11-01

    The effect of experimental diabetes on the phosphorylation of proteins in the rat sciatic nerve was studied. Nerves from animals made diabetic with streptozocin were incubated in vitro with (/sup 32/P)orthophosphate and divided into segments from the proximal to the distal end, and proteins from each segment were then separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The principal labeled species were the major myelin proteins, P0, and the basic proteins. After 6 wk of diabetes, the incorporation of isotope into these proteins rose as a function of distance along the nerve in a proximal to distal direction and was significantly higher at the distal end compared with incorporation into nerves from age-matched controls. The overall level of isotope uptake was similar in nerves from diabetic animals and weight-matched controls. The distribution of /sup 32/P among proteins also differed in diabetic nerve compared with both control groups in that P0 and the small basic protein accounted for a greater proportion of total label incorporated along the entire length of nerve. In contrast to intact nerve, there was no significant difference in protein phosphorylation when homogenates from normal and diabetic nerve were incubated with (/sup 32/P)-gamma-ATP. The results suggest that abnormal protein phosphorylation, particularly of myelin proteins, is a feature of experimental diabetic neuropathy and that the changes are most pronounced in the distal portion of the nerve.

  7. Diabetic autonomic neuropathy.

    PubMed

    Vinik, Aaron I; Erbas, Tomris

    2013-01-01

    Autonomic neuropathy, once considered to be the Cinderella of diabetes complications, has come of age. The autonomic nervous system innervates the entire human body, and is involved in the regulation of every single organ in the body. Thus, perturbations in autonomic function account for everything from abnormalities in pupillary function to gastroparesis, intestinal dysmotility, diabetic diarrhea, genitourinary dysfunction, amongst others. "Know autonomic function and one knows the whole of medicine!" It is now becoming apparent that before the advent of severe pathological damage to the autonomic nervous system there may be an imbalance between the two major arms, namely the sympathetic and parasympathetic nerve fibers that innervate the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. Cardiac autonomic neuropathy (CAN) has been linked to resting tachycardia, postural hypotension, orthostatic bradycardia and orthostatic tachycardia (POTTS), exercise intolerance, decreased hypoxia-induced respiratory drive, loss of baroreceptor sensitivity, enhanced intraoperative or perioperative cardiovascular lability, increased incidence of asymptomatic ischemia, myocardial infarction, and decreased rate of survival after myocardial infarction and congestive heart failure. Autonomic dysfunction can affect daily activities of individuals with diabetes and may invoke potentially life-threatening outcomes. Intensification of glycemic control in the presence of autonomic dysfunction (more so if combined with peripheral neuropathy) increases the likelihood of sudden death and is a caveat for aggressive glycemic control. Advances in technology, built on decades of research and clinical testing, now make it possible to objectively identify early stages of CAN with the use of careful measurement of time and frequency domain analyses of autonomic function. Fifteen studies using different end points report prevalence rates of 1% to 90

  8. Radiation optic neuropathy

    SciTech Connect

    Kline, L.B.; Kim, J.Y.; Ceballos, R.

    1985-08-01

    Following surgery for pituitary adenoma, radiation therapy is an accepted treatment in reducing tumor recurrence. However, a potential therapeutic complication is delayed radionecrosis of perisellar neural structures, including the optic nerves and chiasm. This particular cause of visual loss, radiation optic neuropathy (RON), has not been emphasized in the ophthalmologic literature. Four cases of RON seen in the past five years are reported. Diagnostic criteria include: (1) acute visual loss (monocular or binocular), (2) visual field defects indicating optic nerve or chiasmal dysfunction, (3) absence of optic disc edema, (4) onset usually within three years of therapy (peak: 1-1 1/2 years), and (5) no computed tomographic evidence of visual pathway compression. Pathologic findings, differential diagnosis and therapy will be discussed in outlining the clinical profile of RON.

  9. Rutin ameliorates diabetic neuropathy by lowering plasma glucose and decreasing oxidative stress via Nrf2 signaling pathway in rats.

    PubMed

    Tian, Ruifeng; Yang, Wenqing; Xue, Qiang; Gao, Liang; Huo, Junli; Ren, Dongqing; Chen, Xiaoyan

    2016-01-15

    Rutin exhibits antidiabetic, antioxidant and anti-inflammatory properties, which makes rutin an attractive candidate for diabetic complications. The present study was designed to investigate the potential effect of rutin on diabetic neuropathy. After induction of diabetic neuropathy, rutin (5mg/kg, 25mg/kg and 50mg/kg) were daily given to the diabetic rats for 2 weeks. At the end of rutin administration, rutin produced a significant inhibition of mechanical hyperalgesia, thermal hyperalgesia and cold allodynia, as well as partial restoration of nerve conduction velocities in diabetic rats. Furthermore, rutin significantly increased Na(+), K(+)-ATPase activities in sciatic nerves and decreased caspase-3 expression in dorsal root ganglions (DRG). In addition, rutin significantly decreased plasma glucose, attenuated oxidative stress and neuroinflammation. Further studies showed that rutin significantly increased hydrogen sulfide (H2S) level, up-regulated the expression of nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in DRG. The evidences suggest the beneficial effect of rutin on diabetic neuropathy. Additionally, insulin (2 IU) and BG-12 (15mg/kg) were used to investigate the mechanisms underlying the beneficial effect of rutin on diabetic neuropathy. Insulin achieved lower plasma glucose and BG-12 achieved comparable Nrf2 expression than/to rutin (50mg/kg), respectively. In contrast, the beneficial effect of insulin and BG-12 was inferior to that of rutin (50mg/kg), suggesting that both lowered plasma glucose and Nrf2 signaling contribute to the beneficial effect of rutin on diabetic neuropathy. In conclusion, rutin produces significant protection in diabetic neuropathy, which makes it an attractive candidate for the treatment of diabetic neuropathy.

  10. Posterior interosseous neuropathy

    PubMed Central

    Kele, Henrich; Xia, Annie; Weiler, Markus; Schwarz, Daniel; Bendszus, Martin; Pham, Mirko

    2016-01-01

    Objective: To investigate the spatial pattern of lesion dispersion in posterior interosseous neuropathy syndrome (PINS) by high-resolution magnetic resonance neurography. Methods: This prospective study was approved by the local ethics committee and written informed consent was obtained from all patients. In 19 patients with PINS and 20 healthy controls, a standardized magnetic resonance neurography protocol at 3-tesla was performed with coverage of the upper arm and elbow (T2-weighted fat-saturated: echo time/repetition time 52/7,020 milliseconds, in-plane resolution 0.27 × 0.27 mm2). Lesion classification of the radial nerve trunk and its deep branch (which becomes the posterior interosseous nerve) was performed by visual rating and additional quantitative analysis of normalized T2 signal of radial nerve voxels. Results: Of 19 patients with PINS, only 3 (16%) had a focal neuropathy at the entry of the radial nerve deep branch into the supinator muscle at elbow/forearm level. The other 16 (84%) had proximal radial nerve lesions at the upper arm level with a predominant lesion focus 8.3 ± 4.6 cm proximal to the humeroradial joint. Most of these lesions (75%) followed a specific somatotopic pattern, involving only those fascicles that would form the posterior interosseous nerve more distally. Conclusions: PINS is not necessarily caused by focal compression at the supinator muscle but is instead frequently a consequence of partial fascicular lesions of the radial nerve trunk at the upper arm level. Neuroimaging should be considered as a complementary diagnostic method in PINS. PMID:27683851

  11. Peripheral Neuropathy and Agent Orange

    MedlinePlus

    ... Z) Hepatitis HIV Mental Health Mental Health Home Suicide Prevention Substance Abuse Military Sexual Trauma PTSD Research ( ... eligible for a free Agent Orange registry health exam . Research on peripheral neuropathy and herbicides The Health ...

  12. Pathology of human diabetic neuropathy.

    PubMed

    Malik, R A

    2014-01-01

    Pathologic study of a disease provides insights into the precise mechanisms and targets of damage and may provide insights into new therapies. The main targets in diabetic neuropathy are myelinated and unmyelinated fibers as dysfunction and damage to them explains the symptoms of painful neuropathy and the major end points of foot ulceration and amputation as well as mortality. Demyelination and axonal degeneration are established hallmarks of the pathology of human diabetic neuropathy and were derived from pioneering light and electronmicroscopic studies of sural nerve biopsies in the late 1960s and early 1970s. Additional abnormalities, which are relevant to the pathogenesis of human diabetic neuropathy, include pathology of the microvessels and extracellular space. Intraepidermal and sudomotor nerve quantification in skin biopsies provides a minimally invasive means for the detection of early nerve damage. Studies of muscle biopsies are limited and show significant alterations in the expression of neurotrophins, but limited changes in muscle fiber size and capillary density.

  13. Mitochondrial dynamics and peripheral neuropathy.

    PubMed

    Baloh, Robert H

    2008-02-01

    Peripheral neuropathy is perhaps the archetypal disease of axonal degeneration, characteristically involving degeneration of the longest axons in the body. Evidence from both inherited and acquired forms of peripheral neuropathy strongly supports that the primary pathology is in the axons themselves and points to disruption of axonal transport as an important disease mechanism. Recent studies in human genetics have further identified abnormalities in mitochondrial dynamics--the fusion, fission, and movement of mitochondria--as a player in the pathogenesis of inherited peripheral neuropathy. This review provides an update on the mechanisms of mitochondrial trafficking in axons and the emerging relationship between the disruption of mitochondrial dynamics and axonal degeneration. Evidence suggests mitochondria are a "critical cargo" whose transport is necessary for proper axonal and synaptic function. Importantly, understanding the regulation of mitochondrial movement and the consequences of decreased axonal mitochondrial function may define new paths for therapeutic agents in peripheral neuropathy and other neurodegenerative diseases.

  14. Phosphodiesterase-5 is a therapeutic target for peripheral neuropathy in diabetic mice.

    PubMed

    Wang, L; Chopp, M; Szalad, A; Liu, Z; Bolz, M; Alvarez, F M; Lu, M; Zhang, L; Cui, Y; Zhang, R L; Zhang, Z G

    2011-10-13

    Peripheral neuropathy is a common and major complication of diabetes, the underlying mechanisms of which are not fully understood. Using a mouse model of type II diabetes, the present study investigated the role of phosphodiesterase-5 (PDE5) in peripheral neuropathy. BKS.Cg-m+/+Leprdb/J (db/db) mice were treated with sildenafil, a specific inhibitor of PDE5, at doses of 2 and 10 mg/kg or saline. Levels of PDE5 and morphometric parameters in sciatic nerve tissue as well as the motor and sensory function were measured in these mice. In diabetic mice, PDE5 expression in sciatic nerve tissue was significantly upregulated, whereas the myelin sheath thickness, myelin basic protein (MBP), and subcutaneous nerve fibers were significantly reduced. Treatment with sildenafil significantly improved neurological function, assayed by motor and sensory conducting velocities and thermal and mechanical noxious stimuli, concomitantly with increases in myelin sheath thickness, MBP levels, and subcutaneous nerve fibers. In vitro, hyperglycemia upregulated PDE5 in Schwann cells and reduced Schwann cell proliferation, migration, and expression of brain-derived neurotrophic factor (BDNF). Blockage of PDE5 with sildenafil increased cyclic guanosine monophosphate (cGMP) and completely abolished the effect of hyperglycemia on Schwann cells. Sildenafil upregulated cGMP-dependent protein kinase G I (PKGI), whereas inhibition of PKGI with a PKG inhibitor, KT5823, suppressed the inhibitory effect of sildenafil on Schwann cells. These data indicate that hyperglycemia substantially upregulates PDE5 expression and that the cGMP/PKG signaling pathway activated by sildenafil mediates the beneficial effects of sildenafil on diabetic peripheral neuropathy.

  15. Gosha-jinki-gan (herbal medicine) in streptozocin-induced diabetic neuropathy.

    PubMed

    Nishizawa, M; Sutherland, W H; Nukada, H

    1995-10-01

    Long-established systems of traditional medicine have evolved from systematic recordings of human experience over several millennia. Although not strictly based on concepts of modern science, they nevertheless are founded on a corpus of organised knowledge written in documents, and the evident conclusion is that the alleged "trial and error" methodology has provided useful drugs for humans. Herbal medicine should be investigated as a potential regimen for diabetic neuropathy for the following reasons: (1) diabetic neuropathy remains an important clinical problem affecting a significant proportion of diabetic subjects without satisfactory treatment; (2) there are multiple pathogenetic mechanisms in diabetic neuropathy; and (3) herbal medicine which is a combination prescription has unique synergistic and synthetic effects that result from interactions between individual herbal components, and may induce a wide range of therapeutic potential and utility. Gosha-jinki-gan (GJK), consisting of 10 herbs, has been widely used for a regimen of diabetic complications, including neuropathy, in Japan. However, the effect of GJK on experimental diabetic neuropathy has never been previously evaluated. We examined nerve conduction velocity (NCV) and nerve glucose, sorbitol, fructose and myo-inositol levels in streptozocin (STZ)-induced diabetic rats that were treated with GJK. After 1 week of the STZ injection in 7-9-week-old rats, GJK treatment (100 mg/100 g body weight/day) was started orally. At 16 weeks after the STZ injection, the sciatic NCV of GJK-treated diabetic rats improved significantly when compared to non-treated diabetic rats, although they were not yet normalised.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed Central

    Sudoł-Szopińska, Iwona

    2012-01-01

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

  17. Structure and stability of internodal myelin in mouse models of hereditary neuropathy.

    PubMed

    Avila, Robin L; Inouye, Hideyo; Baek, Rena C; Yin, Xinghua; Trapp, Bruce D; Feltri, M Laura; Wrabetz, Lawrence; Kirschner, Daniel A

    2005-11-01

    Peripheral neuropathies often result in abnormalities in the structure of internodal myelin, including changes in period and membrane packing, as observed by electron microscopy (EM). Mutations in the gene that encodes the major adhesive structural protein of internodal myelin in the peripheral nervous system of humans and mice--P0 glycoprotein--correlate with these defects. The mechanisms by which P0 mutations interfere with myelin packing and stability are not well understood and cannot be provided by EM studies that give static and qualitative information on fixed material. To gain insights into the pathogenesis of mutant P0, we used x-ray diffraction, which can detect more subtle and dynamic changes in native myelin, to investigate myelin structure in sciatic nerves from murine models of hereditary neuropathies. We used mice with disruption of one or both copies of the P0 gene (models of Charcot-Marie-Tooth-like neuropathy [CMT1B] or Dejerine-Sottas-like neuropathy) and mice with a CMT1B resulting from a transgene encoding P0 with an amino terminal myc-tag. To directly test the structural role of P0, we also examined a mouse that expresses P0 instead of proteolipid protein in central nervous system myelin. To link our findings on unfixed nerves with EM results, we analyzed x-ray patterns from unembedded, aldehyde-fixed nerves and from plastic-embedded nerves. From the x-ray patterns recorded from whole nerves, we assessed the amount of myelin and its quality (i.e. relative thickness and regularity). Among sciatic nerves having different levels of P0, we found that unfixed nerves and, to a lesser extent, fixed but unembedded nerves gave diffraction patterns of sufficient quality to distinguish periods, sometimes differing by a few Angstroms. Certain packing abnormalities were preserved qualitatively by aldehyde fixation, and the relative amount and structural integrity of myelin among nerves could be distinguished. Measurements from the same nerve over time

  18. Sciatic hernia clinically mimicking obturator hernia, missed by ultrasonography: case report.

    PubMed

    Rather, Shiraz Ahmad; Dar, Tanveer Iqbal; Malik, Aijaz Ahmad; Parray, Fazal Q; Ahmad, Mukhtar; Asrar, Syed

    2011-05-01

    Sciatic hernia is a rare pelvic floor hernia that occurs through the greater or lesser sciatic foramen. Sciatic hernias often present as pelvic pain, particularly in women, and diagnosis can be difficult. Sciatic hernia is one of the rarest forms of internal hernia, which can present as signs and symptoms of small bowel obstruction, swelling in the respective gluteal region or pelvic pain. Transabdominal and transgluteal operative approaches, including laparoscopic repair, have been reported. We present a case of left-sided sciatic hernia with incarcerated small bowel as its contents. The hernia was missed by ultrasonography and plain abdominal radiography, but the clinical features were suggestive of an obturator hernia.

  19. 12/15-Lipoxygenase inhibition counteracts MAPK phosphorylation in mouse and cell culture models of diabetic peripheral neuropathy

    PubMed Central

    Stavniichuk, Roman; Obrosov, Alexander A.; Drel, Viktor R.; Nadler, Jerry L.; Obrosova, Irina G.; Yorek, Mark A.

    2013-01-01

    Background Increased mitogen-activated protein kinase (MAPK) phosphorylation has been detected in peripheral nerve of human subjects and animal models with diabetes as well as high-glucose exposed human Schwann cells, and have been implicated in diabetic peripheral neuropathy. In our recent studies, leukocytetype 12/15-lipoxygenase inhibition or gene deficiency alleviated large and small nerve fiber dysfunction, but not intraepidermal nerve fiber loss in streptozotocin-diabetic mice. Methods To address a mechanism we evaluated the potential for pharmacological 12/15-lipoxygenase inhibition to counteract excessive MAPK phosphorylation in mouse and cell culture models of diabetic neuropathy. C57Bl6/J mice were made diabetic with streptozotocin and maintained with or without the 12/15-lipoxygenase inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC). Human Schwann cells were cultured in 5.5 mM or 30 mM glucose with or without CDC. Results 12(S) HETE concentrations (ELISA), as well as 12/15-lipoxygenase expression and p38 MAPK, ERK, and SAPK/JNK phosphorylation (all by Western blot analysis) were increased in the peripheral nerve and spinal cord of diabetic mice as well as in high glucose-exposed human Schwann cells. CDC counteracted diabetes-induced increase in 12(S)HETE concentrations (a measure of 12/15-lipoxygenase activity), but not 12/15-lipoxygenase overexpression, in sciatic nerve and spinal cord. The inhibitor blunted excessive p38 MAPK and ERK, but not SAPK/ JNK, phosphorylation in sciatic nerve and high glucose exposed human Schwann cells, but did not affect MAPK, ERK, and SAPK/JNK phosphorylation in spinal cord. Conclusion 12/15-lipoxygenase inhibition counteracts diabetes related MAPK phosphorylation in mouse and cell culture models of diabetic neuropathy and implies that 12/15-lipoxygenase inhibitors may be an effective treatment for diabetic peripheral neuropathy. PMID:24175152

  20. 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

  1. Parthenolide Relieves Pain and Promotes M2 Microglia/Macrophage Polarization in Rat Model of Neuropathy.

    PubMed

    Popiolek-Barczyk, Katarzyna; Kolosowska, Natalia; Piotrowska, Anna; Makuch, Wioletta; Rojewska, Ewelina; Jurga, Agnieszka M; Pilat, Dominika; Mika, Joanna

    2015-01-01

    Neuropathic pain treatment remains a challenge because pathomechanism is not fully understood. It is believed that glial activation and increased spinal nociceptive factors are crucial for neuropathy. We investigated the effect of parthenolide (PTL) on the chronic constriction injury to the sciatic nerve (CCI)-induced neuropathy in rat. We analyzed spinal changes in glial markers and M1 and M2 polarization factors, as well as intracellular signaling pathways. PTL (5 µg; i.t.) was preemptively and then daily administered for 7 days after CCI. PTL attenuated the allodynia and hyperalgesia and increased the protein level of IBA1 (a microglial/macrophage marker) but did not change GFAP (an astrocyte marker) on day 7 after CCI. PTL reduced the protein level of M1 (IL-1β, IL-18, and iNOS) and enhanced M2 (IL-10, TIMP1) factors. In addition, it downregulated the phosphorylated form of NF-κB, p38MAPK, and ERK1/2 protein level and upregulated STAT3. In primary microglial cell culture we have shown that IL-1β, IL-18, iNOS, IL-6, IL-10, and TIMP1 are of microglial origin. Summing up, PTL directly or indirectly attenuates neuropathy symptoms and promotes M2 microglia/macrophages polarization. We suggest that neuropathic pain therapies should be shifted from blanketed microglia/macrophage suppression toward maintenance of the balance between neuroprotective and neurotoxic microglia/macrophage phenotypes.

  2. Parthenolide Relieves Pain and Promotes M2 Microglia/Macrophage Polarization in Rat Model of Neuropathy

    PubMed Central

    Popiolek-Barczyk, Katarzyna; Kolosowska, Natalia; Makuch, Wioletta; Rojewska, Ewelina; Jurga, Agnieszka M.; Pilat, Dominika

    2015-01-01

    Neuropathic pain treatment remains a challenge because pathomechanism is not fully understood. It is believed that glial activation and increased spinal nociceptive factors are crucial for neuropathy. We investigated the effect of parthenolide (PTL) on the chronic constriction injury to the sciatic nerve (CCI)-induced neuropathy in rat. We analyzed spinal changes in glial markers and M1 and M2 polarization factors, as well as intracellular signaling pathways. PTL (5 µg; i.t.) was preemptively and then daily administered for 7 days after CCI. PTL attenuated the allodynia and hyperalgesia and increased the protein level of IBA1 (a microglial/macrophage marker) but did not change GFAP (an astrocyte marker) on day 7 after CCI. PTL reduced the protein level of M1 (IL-1β, IL-18, and iNOS) and enhanced M2 (IL-10, TIMP1) factors. In addition, it downregulated the phosphorylated form of NF-κB, p38MAPK, and ERK1/2 protein level and upregulated STAT3. In primary microglial cell culture we have shown that IL-1β, IL-18, iNOS, IL-6, IL-10, and TIMP1 are of microglial origin. Summing up, PTL directly or indirectly attenuates neuropathy symptoms and promotes M2 microglia/macrophages polarization. We suggest that neuropathic pain therapies should be shifted from blanketed microglia/macrophage suppression toward maintenance of the balance between neuroprotective and neurotoxic microglia/macrophage phenotypes. PMID:26090236

  3. Hypothyroidism: Can It Cause Peripheral Neuropathy?

    MedlinePlus

    Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ...

  4. Sciatic neuralgia associated with a perineural (Tarlov) cyst

    PubMed Central

    Emary, Peter C.; Taylor, John A.

    2016-01-01

    Perineural (Tarlov) cysts are rare and are usually asymptomatic and an incidental finding on routine spinal imaging. Presented here is a case of sciatic neuralgia in a 56-year-old patient whose clinical symptoms correlated with a lower lumbar perineural cyst. PMID:27713584

  5. Sciatic neuralgia associated with a perineural (Tarlov) cyst.

    PubMed

    Emary, Peter C; Taylor, John A

    2016-09-01

    Perineural (Tarlov) cysts are rare and are usually asymptomatic and an incidental finding on routine spinal imaging. Presented here is a case of sciatic neuralgia in a 56-year-old patient whose clinical symptoms correlated with a lower lumbar perineural cyst.

  6. Crucifixion and median neuropathy

    PubMed Central

    Regan, Jacqueline M; Shahlaie, Kiarash; Watson, Joseph C

    2013-01-01

    Crucifixion as a means of torture and execution was first developed in the 6th century B.C. and remained popular for over 1000 years. Details of the practice, which claimed hundreds of thousands of lives, have intrigued scholars as historical records and archaeological findings from the era are limited. As a result, various aspects of crucifixion, including the type of crosses used, methods of securing victims to crosses, the length of time victims survived on the cross, and the exact mechanisms of death, remain topics of debate. One aspect of crucifixion not previously explored in detail is the characteristic hand posture often depicted in artistic renditions of crucifixion. In this posture, the hand is clenched in a peculiar and characteristic fashion: there is complete failure of flexion of the thumb and index finger with partial failure of flexion of the middle finger. Such a “crucified clench” is depicted across different cultures and from different eras. A review of crucifixion history and techniques, median nerve anatomy and function, and the historical artistic depiction of crucifixion was performed to support the hypothesis that the “crucified clench” results from proximal median neuropathy due to positioning on the cross, rather than from direct trauma of impalement of the hand or wrist. PMID:23785656

  7. Diabetic autonomic neuropathy.

    PubMed

    Vinik, Aaron I; Maser, Raelene E; Mitchell, Braxton D; Freeman, Roy

    2003-05-01

    Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes. Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of DAN has not been fully appreciated. The reported prevalence of DAN varies widely depending on the cohort studied and the methods of assessment. In randomly selected cohorts of asymptomatic individuals with diabetes, approximately 20% had abnormal cardiovascular autonomic function. DAN frequently coexists with other peripheral neuropathies and other diabetic complications, but DAN may be isolated, frequently preceding the detection of other complications. Major clinical manifestations of DAN include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, "brittle diabetes," and hypoglycemic autonomic failure. DAN may affect many organ systems throughout the body (e.g., gastrointestinal [GI], genitourinary, and cardiovascular). GI disturbances (e.g., esophageal enteropathy, gastroparesis, constipation, diarrhea, and fecal incontinence) are common, and any section of the GI tract may be affected. Gastroparesis should be suspected in individuals with erratic glucose control. Upper-GI symptoms should lead to consideration of all possible causes, including autonomic dysfunction. Whereas a radiographic gastric emptying study can definitively establish the diagnosis of gastroparesis, a reasonable approach is to exclude autonomic dysfunction and other known causes of these upper-GI symptoms. Constipation is the most common lower-GI symptom but can alternate with episodes of diarrhea. Diagnostic approaches should rule out autonomic dysfunction and the well-known causes such as neoplasia. Occasionally, anorectal manometry and other specialized tests typically performed by the gastroenterologist may be helpful. DAN is also

  8. Not all neuropathy in diabetes is of diabetic etiology: differential diagnosis of diabetic neuropathy.

    PubMed

    Freeman, Roy

    2009-12-01

    Diabetic peripheral neuropathy is the most common peripheral neuropathy in the developed world; however, not all patients with diabetes and peripheral nerve disease have a peripheral neuropathy caused by diabetes. Several (although not all) studies have drawn attention to the presence of other potential causes of a neuropathy in individuals with diabetes; 10% to 50% of individuals with diabetes may have an additional potential cause of a peripheral neuropathy and some may have more than one cause. Neurotoxic medications, alcohol abuse, vitamin B(12) deficiency, renal disease, chronic inflammatory demyelinating neuropathy, inherited neuropathy, and vasculitis are the most common additional potential causes of a peripheral neuropathy in these series. The most common disorders in the differential diagnosis of a generalized diabetic peripheral neuropathy are discussed in this article. Prospective studies to investigate the prevalence of other disorders that might be responsible for a peripheral neuropathy in individuals with diabetes are warranted.

  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. Genetic heterogeneity of motor neuropathies

    PubMed Central

    Bansagi, Boglarka; Griffin, Helen; Whittaker, Roger G.; Antoniadi, Thalia; Evangelista, Teresinha; Miller, James; Greenslade, Mark; Forester, Natalie; Duff, Jennifer; Bradshaw, Anna; Kleinle, Stephanie; Boczonadi, Veronika; Steele, Hannah; Ramesh, Venkateswaran; Franko, Edit; Pyle, Angela; Lochmüller, Hanns; Chinnery, Patrick F.

    2017-01-01

    Objective: To study the prevalence, molecular cause, and clinical presentation of hereditary motor neuropathies in a large cohort of patients from the North of England. Methods: Detailed neurologic and electrophysiologic assessments and next-generation panel testing or whole exome sequencing were performed in 105 patients with clinical symptoms of distal hereditary motor neuropathy (dHMN, 64 patients), axonal motor neuropathy (motor Charcot-Marie-Tooth disease [CMT2], 16 patients), or complex neurologic disease predominantly affecting the motor nerves (hereditary motor neuropathy plus, 25 patients). Results: The prevalence of dHMN is 2.14 affected individuals per 100,000 inhabitants (95% confidence interval 1.62–2.66) in the North of England. Causative mutations were identified in 26 out of 73 index patients (35.6%). The diagnostic rate in the dHMN subgroup was 32.5%, which is higher than previously reported (20%). We detected a significant defect of neuromuscular transmission in 7 cases and identified potentially causative mutations in 4 patients with multifocal demyelinating motor neuropathy. Conclusions: Many of the genes were shared between dHMN and motor CMT2, indicating identical disease mechanisms; therefore, we suggest changing the classification and including dHMN also as a subcategory of Charcot-Marie-Tooth disease. Abnormal neuromuscular transmission in some genetic forms provides a treatable target to develop therapies. PMID:28251916

  11. Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia.

    PubMed

    Li, Qinwen; Chen, Jianghai; Chen, Yanhua; Cong, Xiaobin; Chen, Zhenbing

    2016-03-01

    In the present study, pathological alterations in neurons of the dorsal root ganglia (DRG) were investigated in a rat model of chronic sciatic nerve compression. The rat model of chronic sciatic nerve compression was established by placing a 1 cm Silastic tube around the right sciatic nerve. Histological examination was performed via Masson's trichrome staining. DRG injury was assessed using Fluoro Ruby (FR) or Fluoro Gold (FG). The expression levels of target genes were examined using reverse transcription‑quantitative polymerase chain reaction, western blot and immunohistochemical analyses. At 3 weeks post‑compression, collagen fiber accumulation was observed in the ipsilateral area and, at 8 weeks, excessive collagen formation with muscle atrophy was observed. The collagen volume fraction gradually and significantly increased following sciatic nerve compression. In the model rats, the numbers of FR‑labeled DRG neurons were significantly higher, relative to the sham‑operated group, however, the numbers of FG‑labeled neurons were similar. In the ipsilateral DRG neurons of the model group, the levels of transforming growth factor‑β1 (TGF‑β1) and connective tissue growth factor (CTGF) were elevated and, surrounding the neurons, the levels of collagen type I were increased, compared with those in the contralateral DRG. In the ipsilateral DRG, chronic nerve compression was associated with significantly higher levels of phosphorylated (p)‑extracellular signal‑regulated kinase 1/2, and significantly lower levels of p‑c‑Jun N‑terminal kinase and p‑p38, compared with those in the contralateral DRGs. Chronic sciatic nerve compression likely induced DRG pathology by upregulating the expression levels of TGF‑β1, CTGF and collagen type I, with involvement of the mitogen‑activated protein kinase signaling pathway.

  12. Peripheral neuropathy in mitochondrial disorders.

    PubMed

    Pareyson, Davide; Piscosquito, Giuseppe; Moroni, Isabella; Salsano, Ettore; Zeviani, Massimo

    2013-10-01

    Why is peripheral neuropathy common but mild in many mitochondrial disorders, and why is it, in some cases, the predominant or only manifestation? Although this question remains largely unanswered, recent advances in cellular and molecular biology have begun to clarify the importance of mitochondrial functioning and distribution in the peripheral nerve. Mutations in proteins involved in mitochondrial dynamics (ie, fusion and fission) frequently result in a Charcot-Marie-Tooth phenotype. Peripheral neuropathies with different phenotypic presentations occur in mitochondrial diseases associated with abnormalities in mitochondrial DNA replication and maintenance, or associated with defects in mitochondrial respiratory chain complex V. Our knowledge of mitochondrial disorders is rapidly growing as new nuclear genes are identified and new phenotypes described. Early diagnosis of mitochondrial disorders, essential to provide appropriate genetic counselling, has become crucial in a few treatable conditions. Recognising and diagnosing an underlying mitochondrial defect in patients presenting with peripheral neuropathy is therefore of paramount importance.

  13. 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

  14. 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.

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

    PubMed

    Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh

    2017-03-09

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

  16. Advances in understanding drug-induced neuropathies.

    PubMed

    Peltier, Amanda C; Russell, James W

    2006-01-01

    Many commonly used medications have neurotoxic adverse effects; the most common of these is peripheral neuropathy. Neuropathy can be a dose-limiting adverse effect for many medications used in life-threatening conditions, such as malignancy and HIV-related disease. Epidemiological evidence supports previous case reports of HMG-CoA reductase inhibitors (or 'statins') causing an axonal sensorimotor neuropathy or a purely small-fibre neuropathy in some patients. The neuropathy improves when the medication is withdrawn. Despite the association between HMG-CoA reductase inhibitors and neuropathy, the risk is low compared with the significant vascular protective benefits. Oxaliplatin, a new platinum chemotherapy agent designed to have fewer adverse effects than other such agents, has been shown to cause a transient initial dysaesthesia in addition to an axonal polyneuropathy. Thalidomide, an old therapy currently being utilised for new therapeutic indications (e.g. treatment of haematological malignancies), is associated with a painful, axonal sensorimotor neuropathy that does not improve on withdrawal of the drug. Nucleoside reverse transcriptase inhibitors are important components of highly active antiretroviral therapy, but are associated with a sensory neuropathy that is likely to be due to a direct effect of these drugs on mitochondrial DNA replication. New research demonstrates that lactate levels may help discriminate between neuropathy caused by nucleoside analogues and HIV-induced neuropathy. Understanding the mechanism of drug-induced neuropathy has led to advances in preventing this disabling condition.

  17. Coffee improves auditory neuropathy in diabetic mice.

    PubMed

    Hong, Bin Na; Yi, Tae Hoo; Park, Raekil; Kim, Sun Yeou; Kang, Tong Ho

    2008-08-29

    Coffee is a widely consumed beverage and has recently received considerable attention for its possible beneficial effects. Auditory neuropathy is a hearing disorder characterized by an abnormal auditory brainstem response. This study examined the auditory neuropathy induced by diabetes and investigated the action of coffee, trigonelline, and caffeine to determine whether they improved diabetic auditory neuropathy in mice. Auditory brainstem responses, auditory middle latency responses, and otoacoustic emissions were evaluated to assess auditory neuropathy. Coffee or trigonelline ameliorated the hearing threshold shift and delayed latency of the auditory evoked potential in diabetic neuropathy. These findings demonstrate that diabetes can produce a mouse model of auditory neuropathy and that coffee consumption potentially facilitates recovery from diabetes-induced auditory neuropathy. Furthermore, the active constituent in coffee may be trigonelline.

  18. 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.

  19. Genetics of isolated auditory neuropathies.

    PubMed

    Del Castillo, Francisco J; Del Castillo, Ignacio

    2012-01-01

    Auditory neuropathies are disorders combining absent or abnormal auditory brainstem responses with preserved otoacoustic emissions and/or cochlear microphonics. These features indicate a normal function of cochlear outer hair cells. Thus, the primary lesion might be located in the inner hair cells, in the auditory nerve or in the intervening synapse. Auditory neuropathy is observed in up to 10 percent of deaf infants and children, either as part of some systemic neurodegenerative diseases or as an isolated entity. Research on the genetic causes of isolated auditory neuropathies has been remarkably successful in the last few years. Here we review the current knowledge on the structure, expression and function of the genes and proteins so far known to be involved in these disorders, as well as the clinical features that are associated with mutations in the different genes. This knowledge is permitting to classify isolated auditory neuropathies into etiologically homogeneous types, so providing clues for the better diagnosis, management and therapy of the affected subjects.

  20. Effect of pre-germinated brown rice intake on diabetic neuropathy in streptozotocin-induced diabetic rats

    PubMed Central

    Usuki, Seigo; Ito, Yukihiko; Morikawa, Keiko; Kise, Mitsuo; Ariga, Toshio; Rivner, Michael; Yu, Robert K

    2007-01-01

    Background To study the effects of a pre-germinated brown rice diet (PR) on diabetic neuropathy in streptozotocin (STZ)-induced diabetic rats. Methods The effects of a PR diet on diabetic neuropathy in STZ-induced diabetic rats were evaluated and compared with those fed brown rice (BR) or white rice (WR) diets with respect to the following parameters: blood-glucose level, motor-nerve conduction velocity (NCV), sciatic-nerve Na+/K+-ATPase activity, and serum homocysteine-thiolactonase (HTase) activity. Results Compared with diabetic rats fed BR or WR diets, those fed a PR diet demonstrated significantly lower blood-glucose levels (p < 0.001), improved NCV (1.2- and 1.3-fold higher, respectively), and increased Na+/K+-ATPase activity (1.6- and 1.7-fold higher, respectively). The PR diet was also able to normalize decreased serum homocysteine levels normally seen in diabetic rats. The increased Na+/K+-ATPase activity observed in rats fed PR diets was associated with elevations in HTase activity (r = 0.913, p < 0.001). The in vitro effect of the total lipid extract from PR bran (TLp) on the Na+/K+-ATPase and HTase activity was also examined. Incubation of homocysteine thiolactone (HT) with low-density lipoprotein (LDL) in vitro resulted in generation of HT-modified LDL, which possessed high potency to inhibit Na+/K+-ATPase activity in the sciatic nerve membrane. The inhibitory effect of HT-modified LDL on Na+/K+-ATPase activity disappeared when TLp was added to the incubation mixture. Furthermore, TLp directly activated the HTase associated with high-density lipoprotein (HDL). Conclusion PR treatment shows efficacy for protecting diabetic deterioration and for improving physiological parameters of diabetic neuropathy in rats, as compared with a BR or WR diet. This effect may be induced by a mechanism whereby PR intake mitigates diabetic neuropathy by one or more factors in the total lipid fraction. The active lipid fraction is able to protect the Na+/K+-ATPase of the

  1. Hereditary sensory neuropathy type I.

    PubMed

    Auer-Grumbach, Michaela

    2008-03-18

    Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin

  2. Piriformis Syndrome With Variant Sciatic Nerve Anatomy: A Case Report.

    PubMed

    Kraus, Emily; Tenforde, Adam S; Beaulieu, Christopher F; Ratliff, John; Fredericson, Michael

    2016-02-01

    A 68-year-old male long distance runner presented with low back and left buttock pain, which eventually progressed to severe and debilitating pain, intermittently radiating to the posterior thigh and foot. A comprehensive workup ruled out possible spine or hip causes of his symptoms. A pelvic magnetic resonance imaging neurogram with complex oblique planes through the piriformis demonstrated variant anatomy of the left sciatic nerve consistent with the clinical diagnosis of piriformis syndrome. The patient ultimately underwent neurolysis with release of the sciatic nerve and partial resection of the piriformis muscle. After surgery the patient reported significant pain reduction and resumed running 3 months later. Piriformis syndrome is uncommon but should be considered in the differential diagnosis for buttock pain. Advanced imaging was essential to guide management.

  3. Evidence of bidirectional flow in the sciatic vasa nervorum.

    PubMed

    Olver, Dylan T; Lacefield, James C; Shoemaker, Kevin J

    2014-07-01

    The purpose of this study was to determine whether bidirectional flow exists in the sciatic vasa nervorum. Images obtained using high-frequency color Doppler ultrasound in duplex imaging mode (Vevo 2100) were studied retroactively. In Fig. 1 (left panel; rat 1), the color Doppler signal and flow-velocity waveforms are indicative of pulsatile flow traveling towards (B) and away (C) from the probe. In the right panel (Fig. 1; rat 2), there appears to be three distinct vessels, reflective of non-pulsatile negative flow (D), and pulsatile positive (E) and negative (F) flows. These data confirm the presence of bidirectional arterial flow in the sciatic vasa nervorum. Investigating bidirectional flow in the intact whole nerve may be helpful in elucidating novel features of nerve blood flow control in healthy and diseased states.

  4. Bilateral persistent sciatic arteries with unilateral complicating aneurysm.

    PubMed

    Aziz, M E; Yusof, N R N; Abdullah, M S; Yusof, A H; Yusof, M I

    2005-08-01

    Persistent sciatic artery is a very uncommon embryological vascular variant. This case report highlights this rare vascular anomaly, diagnostic difficulty, complication and subsequent treatment in a 43-year-old man who presented with sudden onset of right leg pain for a few hours. He was unable to walk because of pain and numbness. Emergency right lower limb angiogram showed a large aneurysm that was initially thought to arise from the right common femoral artery, associated with thrombus formation within the right popliteal artery. A below knee amputation was performed due to worsening ischaemia of the right leg. The persistent right sciatic artery was later obliterated using percutaneous stenting and endovascular grafting, with deployment of two wallstents.

  5. Fluorescent nanoparticles for observing primo vascular system along sciatic nerve.

    PubMed

    Jia, Zhao-Feng; Lee, Byung-Cheon; Eom, Ki-Hoon; Cha, Jin-Myung; Lee, Jin-Kyu; Su, Zhen-Dong; Yu, Wen-Hui; Ryu, Pan Dong; Soh, Kwang-Sup

    2010-09-01

    The primo vascular system was found in the epineurium along the rat sciatic nerve following subcutaneous injection of fluorescent nanoparticles at the Zusanli acupoint (ST-36). Nanoparticles were injected into the primo-vessel near ST-36 and flowed along the sciatic nerve. Fluorescence revealed a structure in the epineurium that was hardly detectable. Images of the isolated sample stained with 4',6-diamidino-2-phenylindole were captured using confocal microscopy. These images showed the distinctive nuclei distribution and multi-lumen structure of primo-vessels that differentiate them from lymphatic vessels, blood capillaries and nerves. This study demonstrates a new use for nanoparticles in fluorescence reflectance imaging techniques during in vivo imaging of primo-vessels.

  6. Effects of ozone on sciatic nerve in rat.

    PubMed

    Lin, Q; Chen, H; Lu, C; Wang, B; Zhang, Y; He, X; Yu, B

    2011-09-01

    This study evaluated the influence of ozone on rat sciatic nerve structure and function. Thirty Wistar rats were randomly divided into six groups (n = 5). In groups I to IV, 1ml of ozone (O(3)) 10 μg/ml, 30 μg/ml, 50 μg/ml, 8 0 μg/ml was injected at the junction of gluteus maximus margin and lateral edge of the long head of biceps femoris respectively, in group V, 1 ml of pure O(2) was injected at the same point, and group V had puncture without any injection. Ozone was manufactured by an ozone generator (Ozone Line Co, Italy). The rats were investigated by both gross measurement and behavioral changes. One day, one week and three weeks after injection, rat hindlimb footprints were measured and the sciatic nerve function index (SFI) was calculated, and after three weeks, all right sciatic nerves were exposed under anesthesia. Near neural stimulation of the rat sciatic nerve was calculated and nerve conduction velocity, latency and maximum amplitude recorded. Animals were sacrificed for pathology, and ipsilateral triceps surae were taken for wet weight. No serious behavioral abnormalities were observed in any animal. SFI comparison in the various times and various groups showed no significant differences (p<0.05), and nerve conduction velocity, latency and maximum amplitude difference amongst the groups was not significant (p<0.05). There were no abnormalities in peripheral nerves pathologically after injection. Our initial study suggests that ozone concentrations from 10 μg/ml to 80 μg/ml injected around rat's peripheral nerve will not cause serious sequelae or serious damage to the structure and function of peripheral nerve. This finding provides evidence of the safety of ozone injected around the peripheral nerve.

  7. A rare case of segmental neurofibromatosis involving the sciatic nerve.

    PubMed

    Trocchia, Aron; Reyes, Alma; Wilson, Jon; Les, Kimberly

    2010-05-01

    Segmental neurofibromatosis (NF-5) is an extremely rare variant of neurofibromatosis involving a single extremity without pathologic features beyond the midline. A case of segmental neurofibromatosis involving the sciatic nerve and its branches is presented with a detailed description of the patient's preoperative findings plus postoperative course through 1-year follow-up. Clinical, histologic, and genetic findings are given along with a brief review of the literature on segmental neurofibromatosis. Last, treatment options and postoperative care recommendations are provided.

  8. CONSERVATIVE REHABILITATION OF SCIATIC NERVE INJURY FOLLOWING HAMSTRING TEAR

    PubMed Central

    Reuteman, Paul

    2010-01-01

    Study Design: Resident's case report Background: There have been only a few case reports in the literature mentioning sciatic nerve injury following a hamstring tear. In previous cases surgical intervention was performed to debride scar tissue around the sciatic nerve with the goal of full return to function for the patient. Objectives: The purpose of this case report is to describe the conservative interventions that allowed for recovery from a hamstring tear with sciatic nerve involvement. Case Description: The subject was a 53 year old female who developed foot drop and weakness in the common fibular nerve distribution following a grade 3 hamstring injury sustained during Nordic skiing. Nerve function and strength gradually returned over the course of several months of conservative rehabilitation which included on neural gliding and strengthening exercises. Outcomes: At 18 months post injury, the subject had returned to 95% of full sport function and 98% of full function with activities of daily living, as rated by the Hip Outcome Scale, and had full strength with manual muscle testing. Isokinetic testing revealed strength deficits of 11–23% in knee flexion peak torque at 60 degrees/second and 180 degrees/second respectively. Discussion: Sciatic nerve injury is a rare, but important potential consequence of severe hamstring strains. Clinicians should be cognizant of the potential injury to the nerve tissue following hamstring strains, so they may be dealt with in a prompt and appropriate manner. The use of neural gliding may be worth considering for a prophylactic effect following hamstring strains. PMID:21589670

  9. 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.

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

    SciTech Connect

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

    1991-04-01

    Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers and perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy.

  11. Epidermal Laser Stimulation of Action Potentials in the Frog Sciatic Nerve

    DTIC Science & Technology

    2008-10-01

    Laser Stimulation of Action Potentials in the Frog Sciatic Nerve Nichole M. Jindra Robert J. Thomas Human Effectiveness Directorate Directed...in the Frog Sciatic Nerve 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62202F 6. AUTHOR(S) .Nichole M. Jindra, Robert J. Thomas, Douglas N...Alan Rice 14. ABSTRACT Measurements of laser stimulated action potentials in the sciatic nerve of leopard frogs (Rana pipiens) were made using

  12. Endovascular Treatment of Common Iliac Occlusion in the Presence of Persistent Sciatic Artery

    SciTech Connect

    Mofidi, R. Macaskill, E. J.; Griffiths, G. D.; Chakraverty, S.

    2008-07-15

    Persistent sciatic artery is a rare congenital anomaly. It is associated with increased incidence of aneurysmal dilatation, thrombosis, distal embolization, and atherosclerotic change. We describe the case of a patient with persistent sciatic artery who presented with a critically ischemic left leg as a result of an occluded left common iliac artery, which was treated by angioplasty and stenting, and discuss the endovascular iliac recanalization in the presence of a persistent sciatic artery.

  13. Experimental Alcohol-Related Peripheral Neuropathy: Role of Insulin/IGF Resistance

    PubMed Central

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

    2012-01-01

    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. PMID:23016131

  14. Ameliorative effect of Vernonia cinerea in vincristine-induced painful neuropathy in rats.

    PubMed

    Thiagarajan, Venkata Rathina Kumar; Shanmugam, Palanichamy; Krishnan, Uma Maheswari; Muthuraman, Arunachalam

    2014-10-01

    The present study was designed to investigate the antinociceptive potential of Vernonia cinerea (VC) on vincristine-induced painful neuropathy in rats. A chemotherapeutic agent, vincristine (50 μg/kg intraperitoneally for 10 consecutive days), was administered for the induction of neuropathic pain in rats. The painful behavioral changes were assessed using hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests to assess the degree of hyperalgesic and allodynic pain sensation in paw and tail. Tissue biomarker changes including thiobarbituric acid reactive substances (TBARSs), reduced glutathione (GSH) and total calcium levels were estimated in sciatic nerve tissue samples to assess the degree of oxidative stress. Histopathological changes were also observed in transverse sections of rat sciatic nerve tissue. Ethanolic extract of VC leaves and pregabalin were administered for 14 consecutive days from day 0 (day of surgery). Pregabalin served as a positive control in the present study. Vincristine administration resulted in a significant reduction in painful behavioral changes along with a rise in the levels of TBARS, total calcium and decrease in GSH levels when compared with the normal control group. Furthermore, significant histopathological changes were also observed. Pretreatment with VC significantly attenuated vincristine-induced development of painful behavioral, biochemical and histological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. The attenuating effect of VC in vincristine-induced nociceptive painful sensation may be due to its potential of antioxidative, neuroprotective and calcium channel inhibitory action.

  15. Puerarin accelerates neural regeneration after sciatic nerve injury

    PubMed Central

    Wu, Minfei; Zhao, Guanjie; Yang, Xiaoyu; Peng, Chuangang; Zhao, Jianwu; Liu, Jun; Li, Rui; Gao, Zhongli

    2014-01-01

    Puerarin is a natural isoflavone isolated from plants of the genus Pueraria and functions as a protector against cerebral ischemia. We hypothesized that puerarin can be involved in the repair of peripheral nerve injuries. To test this hypothesis, doses of 10, 5, or 2.5 mg/kg per day puerarin (8-(β-D-Glucopyranosyl-7-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) were injected intraperitoneally into mouse models of sciatic nerve injury. Puerarin at the middle and high doses significantly up-regulated the expression of growth-associated protein 43 in the L4–6 segments of the spinal cord from mice at 1, 2, and 4 weeks after modeling, and reduced the atrophy of the triceps surae on the affected side and promoted the regeneration of nerve fibers of the damaged spinal cord at 8 weeks after injury. We conclude that puerarin exerts an ongoing role to activate growth-associated protein 43 in the corresponding segment of the spinal cord after sciatic nerve injury, thus contributing to neural regeneration after sciatic nerve injuries. PMID:25206860

  16. Idiopathic neuropathy, prediabetes and the metabolic syndrome.

    PubMed

    Gordon Smith, A; Robinson Singleton, J

    2006-03-15

    Peripheral neuropathy is a common problem encountered by neurologists and primary care physicians. While there are many causes for peripheral neuropathy, none can be identified in a large percentage of patients ("idiopathic neuropathy"). Despite its high prevalence, idiopathic neuropathy is poorly studied and understood. There is evolving evidence that impaired glucose tolerance (prediabetes) is associated with idiopathic neuropathy. Preliminary data from a multicenter study of diet and exercise in prediabetes (the Impaired Glucose Tolerance Neuropathy Study) suggests a diet and exercise counseling regimen based on the Diabetes Prevention Program results in improved metabolic measures and small fiber function. Prediabetes is part of the Metabolic Syndrome, which also includes hypertension, hyperlipidemia and obesity. Individual aspects of the Metabolic Syndrome influence risk and progression of diabetic neuropathy and may play a causative role in neuropathy both for those with prediabetes, and those with otherwise idiopathic neuropathy. Thus, a multifactorial treatment approach to individual components of Metabolic Syndrome may slow prediabetic neuropathy progression or result in improvement.

  17. The sciatic nerve in human cadavers - high division or low formation?

    PubMed

    Khan, A A; Asari, M A; Pasha, M A

    2016-01-01

    Variations of the sciatic nerve have been extensively studied in the past including its relationship with the piriformis muscle and associated clinical conditions like piriformis syndrome and sciatica. In the present study we noticed some interesting variations of the sciatic nerve, which were slightly different from the cases described earlier. In the previous studies most of the authors described the higher division of sciatic nerve and none of them discussed its formation. In this study we tried to look its formation from the sacral plexus and its divisions in the thigh. We noticed that in one cadaver the two components of the sciatic nerve originated directly from the sacral plexus and coursed down without merging in the thigh. Should this be called a higher division or non formation of the sciatic nerve? On the other hand in two other cadavers, the two divisions after emerging separately from the sacral plexus, united in the gluteal region and in the thigh respectively. Should we call this as higher division or low formation of the sciatic nerve? In two other cadavers the sciatic nerve emerged from the greater sciatic foramen below the piriformis and divided in the gluteal region itself. Ideally this should be called as higher division of sciatic nerve.

  18. Poly(lactic-co-glycolic acid) conduit for repair of injured sciatic nerve: A mechanical analysis

    PubMed Central

    Yu, Tao; Zhao, Changfu; Li, Peng; Liu, Guangyao; Luo, Min

    2013-01-01

    Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly(lactic-co-glycolic acid) conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study collected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, following which poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly(lactic-co-glycolic acid) conduit-repaired sciatic nerve following tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Following poly(lactic-co-glycolic acid) conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogenous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly(lactic-co-glycolic acid) conduits exhibited good intensity, elasticity and plasticity, indicating that poly(lactic-co-glycolic acid) conduits are suitable for sciatic nerve injury repair. PMID:25206505

  19. Poly(lactic-co-glycolic acid) conduit for repair of injured sciatic nerve: A mechanical analysis.

    PubMed

    Yu, Tao; Zhao, Changfu; Li, Peng; Liu, Guangyao; Luo, Min

    2013-07-25

    Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly(lactic-co-glycolic acid) conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study collected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, following which poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly(lactic-co-glycolic acid) conduit-repaired sciatic nerve following tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Following poly(lactic-co-glycolic acid) conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogenous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly(lactic-co-glycolic acid) conduits exhibited good intensity, elasticity and plasticity, indicating that poly(lactic-co-glycolic acid) conduits are suitable for sciatic nerve injury repair.

  20. Genetics Home Reference: hereditary sensory neuropathy type IA

    MedlinePlus

    ... by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition experience prickling or ... Research Network: Inherited Neuropathies Consortium The Foundation for Peripheral Neuropathy: Symptoms General Information from MedlinePlus (5 links) Diagnostic ...

  1. Genetics Home Reference: hereditary sensory and autonomic neuropathy type II

    MedlinePlus

    ... Diseases Clinical Research Network: The Inherited Neuropathies Consortium Educational Resources (2 links) Orphanet: Hereditary sensory and autonomic neuropathy type 2 University of Chicago Center for Peripheral Neuropathy Patient Support ...

  2. Genetics Home Reference: distal hereditary motor neuropathy, type II

    MedlinePlus

    ... distal hereditary motor neuropathy, type II distal hereditary motor neuropathy, type II Enable Javascript to view the ... PDF Open All Close All Description Distal hereditary motor neuropathy, type II is a progressive disorder that ...

  3. Animal Models of Autoimmune Neuropathy

    PubMed Central

    Soliven, Betty

    2014-01-01

    The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy have been provided by ex vivo immunologic studies, biopsy materials, electrophysiologic studies, and experimental models. This review article summarizes earlier seminal observations and highlights the recent progress in our understanding of immunopathogenesis of autoimmune neuropathies based on data from animal models. PMID:24615441

  4. Electrospun Nanofibers Loaded with Quercetin Promote the Recovery of Focal Entrapment Neuropathy in a Rat Model of Streptozotocin-Induced Diabetes.

    PubMed

    Thipkaew, Chonlathip; Wattanathorn, Jintanaporn; Muchimapura, Supaporn

    2017-01-01

    In this study, quercetin-loaded zein-based nanofibers were developed using electrospinning technique. The therapeutic effect of these quercetin-loaded nanofibers on neuropathy in streptozotocin- (STZ-) induced diabetes in rats was assessed. Diabetic condition was induced in male Wistar rats by STZ, after which a crush injury of the right sciatic nerve was performed to induce mononeuropathy. Functional recovery was assessed using walking track analysis, measurements of foot withdrawal reflex, nerve conduction velocity, and morphological analysis. The oxidative stress status and the ratio of phosphorylated extracellular recognition kinase (pERK)/extracellular recognition kinase (ERK) expression in the nerve lesion were also assessed in order to elucidate the potential mechanisms involved. Results showed that quercetin-loaded zein-based nanofibers slightly enhanced functional recovery from neuropathy in STZ-diabetic rats. The potential mechanism might partially involve improvements in oxidative stress status and the ratio of pERK/ERK expression in the nerve lesion.

  5. Electrospun Nanofibers Loaded with Quercetin Promote the Recovery of Focal Entrapment Neuropathy in a Rat Model of Streptozotocin-Induced Diabetes

    PubMed Central

    Thipkaew, Chonlathip

    2017-01-01

    In this study, quercetin-loaded zein-based nanofibers were developed using electrospinning technique. The therapeutic effect of these quercetin-loaded nanofibers on neuropathy in streptozotocin- (STZ-) induced diabetes in rats was assessed. Diabetic condition was induced in male Wistar rats by STZ, after which a crush injury of the right sciatic nerve was performed to induce mononeuropathy. Functional recovery was assessed using walking track analysis, measurements of foot withdrawal reflex, nerve conduction velocity, and morphological analysis. The oxidative stress status and the ratio of phosphorylated extracellular recognition kinase (pERK)/extracellular recognition kinase (ERK) expression in the nerve lesion were also assessed in order to elucidate the potential mechanisms involved. Results showed that quercetin-loaded zein-based nanofibers slightly enhanced functional recovery from neuropathy in STZ-diabetic rats. The potential mechanism might partially involve improvements in oxidative stress status and the ratio of pERK/ERK expression in the nerve lesion. PMID:28251151

  6. Painful diabetic neuropathy: clinical aspects.

    PubMed

    Didangelos, Triantafyllos; Doupis, John; Veves, Aristidis

    2014-01-01

    Painful diabetic neuropathy (PDN) is one of several clinical syndromes in patients with diabetic peripheral neuropathy (DPN) and presents a major challenge for optimal management. The epidemiology of PDN has not been extensively studied. On the basis of available data, the prevalence of pain ranges from 10% to 20% in patients with diabetes and from 40% to 50% in those with diabetic neuropathy. Neuropathic pain can be disabling and devastating, with a significant impact on the patient's quality of life and associated healthcare cost. Pathophysiologic mechanisms underlying PDN are similar to other neuropathic pain disorders and broadly invoke peripheral and central sensitization. The natural course of PDN is variable, with the majority of patients experiencing spontaneous improvement and resolution of pain. Quantifying neuropathic pain is difficult, especially in clinical practice, but has improved recently in clinical trials with the development of neuropathic pain-specific tools, such as the Neuropathic Pain Questionnaire and the Neuropathic Pain Symptom Inventory. Hyperglycemia-induced pathways result in nerve dysfunction and damage, which lead to hyperexcitable peripheral and central pathways of pain. Glycemic control may prevent or partially reverse DPN and modulate PDN.

  7. The response of spinal microglia to chemotherapy-evoked painful peripheral neuropathies is distinct from that evoked by traumatic nerve injuries

    PubMed Central

    Zheng, F. Y.; Xiao, W.-H.; Bennett, G. J.

    2011-01-01

    Painful peripheral neuropathies produced by nerve trauma are accompanied by substantial axonal degeneration and by a response in spinal cord microglia that is characterized by hypertrophy and increased expression of several intracellular and cell-surface markers, including ionizing calcium-binding adapter molecule 1 (Iba1) and Cd11b (a complement receptor 3 antigen recognized by the OX42 antibody). The microglia response has been hypothesized to be essential for the pathogenesis of the neuropathic pain state. In contrast, the painful peripheral neuropathies produced by low doses of cancer chemotherapeutics do not produce degeneration of axons in the peripheral nerve, although they do cause partial degeneration of the sensory axons’ distal-most tips, i.e. the intraepidermal nerve fibers that form the axons’ terminal receptor arbors. The question thus arises as to whether the relatively minor and distal axonal injury characterizing the chemotherapy-evoked neuropathies is sufficient to evoke the microglial response that is seen after traumatic nerve injury. We examined the lumbar spinal cord of rats with painful peripheral neuropathies due to the anti-neoplastic agents, paclitaxel, vincristine, and oxaliplatin, and the anti-retroviral agent, 2′,3′-dideoxycytidine (ddC), and compared them to rats with a complete sciatic nerve transection and the partial sciatic nerve injury produced in the chronic constriction injury model (CCI). As expected, microglia hypertrophy and increased expression of Iba1 were pronounced in the nerve transection and CCI animals. However, there was no microglia hypertrophy or increased Iba1 staining in the animals treated with paclitaxel, vincristine, oxaliplatin, or ddC. These results suggest that the mechanisms that produce neuropathic pain after exposure to chemotherapeutics may be fundamentally different than those operating after nerve trauma. PMID:21195745

  8. 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.

  9. Assessment of 3-nitropropionic acid-evoked peripheral neuropathy in rats: neuroprotective effects of acetyl-l-carnitine and resveratrol.

    PubMed

    Binienda, Zbigniew K; Beaudoin, Micheal A; Gough, Bobby; Ali, Syed F; Virmani, Ashraf

    2010-08-16

    Oxidative stress and secondary excitotoxicity, due to cellular energy deficit, are major factors playing roles in 3-nitropropionic acid (3-NPA) induced mitochondrial dysfunction. Acute or chronic exposure to 3-NPA also leads to neuronal degeneration in different brain regions. The present study quantitatively assessed peripheral neuropathy induced by chronic exposure to 3-NPA in rats. The neuroprotective abilities of two antioxidants, acetyl-l-carnitine and resveratrol, were investigated as well. Rats were exposed for up to four weeks to 3-NPA alone or 3-NPA combined with acetyl-l-carnitine or resveratrol, administered peripherally. The experimental outcome was evaluated by neurophysiological, histological, and morphometric analyses. Rats exposed to 3-NPA developed hind limb paresis. Furthermore, a significant decrease in motor nerve conduction velocity (MCV) was detected in tail nerves and axonal degeneration in sciatic nerves (p<0.05). Treatment with resveratrol prevented the functional effects of 3-NPA exposure, whereas treatment with acetyl-l-carnitine, preventing paresis, was not effective to MCV and morphological changes. These data suggest that resveratrol is a good candidate for treatment of metabolic neuropathy. The experimental outcome of this study shows that chronic treatment with 3-NPA in rats is relevant in development of an experimental model of toxic neuropathy.

  10. [Delayed paresis of the femoral nerve after total hip arthroplasty associated with hereditary neuropathy with liability to pressure palsies (HNPP)].

    PubMed

    Schuh, A; Dürr, V; Weier, H; Zeiler, G; Winterholler, M

    2004-07-01

    Delayed lesions of the femoral or sciatic nerve are a rare complication after total hip arthroplasty. Several cases in association with cement edges, scar tissue, broken cerclages, deep hematoma, or reinforcement rings have been published. We report about a 62-year-old female who developed a pure motor paresis of the quadriceps muscle 2 weeks after total hip arthroplasty. After electrophysiological evaluation had revealed an isolated femoral nerve lesion, revision of the femoral nerve was performed. During operative revision no pathologic findings could be seen. One week later the patient developed paralysis of the left wrist and finger extensors after using crutches. Electrophysiological evaluation revealed several nerve conduction blocks in physiological entrapments and the diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP) was established. Hereditary neuropathy with liability to pressure palsies (HNPP) is a rare disease with increased vulnerability of the peripheral nerve system with mostly reversible sensorimotor deficits. It should be taken into consideration in cases of atypical findings of compression syndromes of peripheral nerves or delayed neuropathy, e. g., after total hip arthroplasty.

  11. Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress.

    PubMed

    Comelli, Francesca; Bettoni, Isabella; Colleoni, Mariapia; Giagnoni, Gabriella; Costa, Barbara

    2009-12-01

    Neuropathy is the most common complication of diabetes and it is still considered to be relatively refractory to most of the analgesics. The aim of the present study was to explore the antinociceptive effect of a controlled cannabis extract (eCBD) in attenuating diabetic neuropathic pain. Repeated treatment with cannabis extract significantly relieved mechanical allodynia and restored the physiological thermal pain perception in streptozotocin (STZ)-induced diabetic rats without affecting hyperglycemia. In addition, the results showed that eCBD increased the reduced glutathione (GSH) content in the liver leading to a restoration of the defence mechanism and significantly decreased the liver lipid peroxidation suggesting that eCBD provides protection against oxidative damage in STZ-induced diabetes that also strongly contributes to the development of neuropathy. Finally, the nerve growth factor content in the sciatic nerve of diabetic rats was restored to normal following the repeated treatment with eCBD, suggesting that the extract was able to prevent the nerve damage caused by the reduced support of this neurotrophin. These findings highlighted the beneficial effects of cannabis extract treatment in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and a specific action upon nerve growth factor.

  12. Assessment of bortezomib induced peripheral neuropathy in multiple myeloma by the reduced Total Neuropathy Score.

    PubMed

    Zaroulis, Chrysothea K; Chairopoulos, Konstantinos; Sachanas, Sotirios P; Maltezas, Dimitris; Tzenou, Tatiana; Pessach, Ilias; Koulieris, Efstathios; Koutra, Eleni; Kilindireas, Konstantinos; Pangalis, Gerasimos A; Kyrtsonis, Marie-Christine

    2014-10-01

    We evaluated bortezomib induced peripheral neuropathy (BIPN) characteristics in an attempt to better clarify the type, grade, duration and reversibility of neuropathy as well as investigate possible peripheral neuropathy (PN) risk factors and detect the best way to manage it. We calculated the grading of neuropathy using the Total Neuropathy Score reduced version (TNSr) in a series of 51 patients with relapsed/refractory multiple myeloma treated with bortezomib. Seventy percent developed clinical PN. BIPN, although manageable, is frequently underestimated in patients treated with bortezomib intravenously. Continuous follow-up and management of PN are needed to avoid quality of life impairment.

  13. Variation in rat sciatic nerve anatomy: implications for a rat model of neuropathic pain.

    PubMed

    Asato, F; Butler, M; Blomberg, H; Gordh, T

    2000-03-01

    We discovered a variation of rat sciatic nerve anatomy as an incidental finding during the anatomical exploration of the nerve lesion site in a rat neuropathic pain model. To confirm the composition and distribution of rat sciatic nerve, macroscopic anatomical investigation was performed in both left and right sides in 24 adult Sprague-Dawley rats. In all rats, the L4 and L5 spinal nerves were fused tightly to form the sciatic nerve. However, the L6 spinal nerve did not fuse with this nerve completely as a part of the sciatic nerve, but rather sent a thin branch to it in 13 rats (54%), whereas in the remaining 11 rats (46%), L6 ran separately along with the sciatic nerve. Also, the L3 spinal nerve sent a thin branch to the L4 spinal nerve or sciatic nerve in 6 rats (25%). We conclude that the components of sciatic nerve in Sprague-Dawley rats vary from L3 to L6; however, the major components are L4 and L5 macroscopically. This finding is in contrast to the standard textbooks of rat anatomy which describe the sciatic nerve as having major contributions from L4, L5, and L6.

  14. Strain differences in the branching of the sciatic nerve in rats.

    PubMed

    Rupp, A; Schmahl, W; Lederer, W; Matiasek, K

    2007-06-01

    The sciatic nerve in the rat is the site most often used for peripheral nerve regeneration studies. The length of sciatic nerve available for research, however, depends on the point at which the sciatic nerve divides into the peroneal and tibial nerves. In the present study, the hind limbs of 150 adult male rats of five different strains (Sprague-Dawley, Fischer 344, Wistar-Han, Lewis and Nude) were analysed with regard to femur length, the point at which the sciatic nerve divides into the tibial and peroneal nerves, and where these are surrounded by the same epineurium, and the point at which they are encased in individual epineurial sheaths. The results indicate that the lengths of sciatic nerve are fairly constant in all strains of rats. In absolute terms, they amount to about one-third of the length of the femur for stretches of undivided sciatic nerve, and up to nearly half of the femur length for stretches where the tibial and peroneal nerves are already present, but are still enclosed by the same epineurium. In 61.7% of the hind limbs examined in Fischer rats, however, no sciatic nerve could be seen as such, but only in the form of its successors surrounded by the separate epineuria. This makes it highly advisable not to use male adult Fischer rats in peripheral nerve regeneration studies with the sciatic nerve as the point of focus.

  15. Inadvertent Embolization of a Persistent Sciatic Artery in Pelvis Trauma

    SciTech Connect

    Hsu, W.-C. Lim, K.-E.; Hsu, Y.-Y.

    2005-05-15

    We describe a case of unilateral persistent sciatic artery (PSA), a rare vascular anomaly, in a 43-year-old woman with severe multiple trauma. A small amount of diluted embolization particles went into this vessel during emergent endovascular therapy under fluoroscopic monitoring. The procedure was immediately stopped when the true nature of the anatomic variant was recognized. Fortunately, an ischemic event of the lower leg did not occur. The imaging findings of computed tomography and digital subtraction angiography are presented and the relevant literature is reviewed.

  16. Toxicity studies on agents Gb and Gd (Phase 2): Delayed neuropathy study of soman in SPF white leghorn chickens. Final technical report, July 1985-August 1991

    SciTech Connect

    Bucci, T.J.; Parker, R.M.; Gosnell, P.A.

    1992-05-01

    A dose rangefinding study, a delayed neuropathy study, and a neurotoxic esterase study, were performed in White Leghorn chickens using the organophosphate ester Soman. The hens used for the Rangefinding study were dosed once orally with 500, 250, 100, 50, 25, or 0 microns g/Kg GD, on Day 1. They were pretreated and protected daily through Day 7 with atropine. Surviving hens were euthanized with sodium pentobarbital on Day 21. The maximum tolerated dose (MTD) to be used in the Delayed Neuropathy Study was chosen based upon the rangefinding data. Fifty hens were assigned to a Single Dose Delayed Neuropathy study. Groups of ten hens were given 14.2 (MTD), 7.1 (MTD/2), 3.5 (MTD/4), 0 (negative control) microns/Kg GD or 51 0 mg/Kg tri-ortho-cresyl phosphate (TOCP) (positive control). Rangefinding study. They were evaluated for signs of neurologic toxicity/ataxia. Necropsy examination was performed on all animals. Sections of cerebellum, medulla, spinal cord (cervical, thoracic, and lumbar), both sciatic nerves and their tibial branch were examined microscopically.... Delayed neuropathy; Agents; Soman; Chickens.

  17. Rikkunshito prevents paclitaxel-induced peripheral neuropathy through the suppression of the nuclear factor kappa B (NFκB) phosphorylation in spinal cord of mice.

    PubMed

    Kamei, Junzo; Hayashi, Shunsuke; Sakai, Akane; Nakanishi, Yuki; Kai, Misa; Ikegami, Megumi; Ikeda, Hiroko

    2017-01-01

    Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB) in the spinal dorsal horn. Rikkunshito (RKT), a kampo medicine, increases the secretion of ghrelin in rodents and humans. Thus, RKT may attenuate paclitaxel-induced peripheral neuropathy by inhibiting phosphorylated NFκB (pNFκB) in the spinal cord. We found that paclitaxel dose-dependently induced mechanical hyperalgesia in mice. Paclitaxel increased the protein levels of spinal pNFκB, but not those of spinal NFκB. NFκB inhibitor attenuated paclitaxel-induced mechanical hyperalgesia suggesting that the activation of NFκB mediates paclitaxel-induced hyperalgesia. RKT dose-dependently attenuated paclitaxel-induced mechanical hyperalgesia. Ghrelin receptor antagonist reversed the RKT-induced attenuation of paclitaxel-induced mechanical hyperalgesia. RKT inhibited the paclitaxel-induced increase in the protein levels of spinal pNFκB. Taken together, the present study indicates that RKT exerts an antihyperalgesic effect in paclitaxel-induced neuropathic pain by suppressing the activation of spinal NFκB.

  18. Decrease in neuroimmune activation by HSV-mediated gene transfer of TNFα soluble receptor alleviates pain in rats with diabetic neuropathy

    PubMed Central

    Maier Ortmann, Kathryn L.; Chattopadhyay, Munmun

    2014-01-01

    The mechanisms of diabetic painful neuropathy are complicated and comprise of peripheral and central pathophysiological phenomena. A number of proinflammatory cytokines are involved in this process. Tumor necrosis factor α (TNF-α) is considered to be one of the major contributors of neuropathic pain. In order to explore the potential role of inflammation in the peripheral nervous system of Type 1 diabetic animals with painful neuropathy, we investigated whether TNF-α is a key inflammatory mediator to the diabetic neuropathic pain and whether continuous delivery of TNFα soluble receptor from damaged axons achieved by HSV vector mediated transduction of DRG would block or alter the pain perception in animals with diabetic neuropathy. Diabetic animals exhibited changes in threshold of mechanical and thermal pain perception compared to control rats and also demonstrated increases in TNFα in the DRG, spinal cord dorsal horn, sciatic nerve and in the foot skin, 6 weeks after the onset of diabetes. Therapeutic approaches by HSV mediated expression of p55 TNF soluble receptor significantly attenuated the diabetes-induced hyperalgesia and decreased the expression of TNFα with reduction in the phosphorylation of p38MAPK in the spinal cord dorsal horn and DRG. The overall outcome of this study suggests that neuroinflammatory activation in the peripheral nervous system may be involved in the pathogenesis of painful neuropathy in Type 1 diabetes which can be alleviated by local expression of HSV vector expressing p55 TNF soluble receptor. PMID:24880032

  19. Decrease in neuroimmune activation by HSV-mediated gene transfer of TNFα soluble receptor alleviates pain in rats with diabetic neuropathy.

    PubMed

    Ortmann, Kathryn L Maier; Chattopadhyay, Munmun

    2014-10-01

    The mechanisms of diabetic painful neuropathy are complicated and comprise of peripheral and central pathophysiological phenomena. A number of proinflammatory cytokines are involved in this process. Tumor necrosis factor α (TNF-α) is considered to be one of the major contributors of neuropathic pain. In order to explore the potential role of inflammation in the peripheral nervous system of Type 1 diabetic animals with painful neuropathy, we investigated whether TNF-α is a key inflammatory mediator to the diabetic neuropathic pain and whether continuous delivery of TNFα soluble receptor from damaged axons achieved by HSV vector mediated transduction of DRG would block or alter the pain perception in animals with diabetic neuropathy. Diabetic animals exhibited changes in threshold of mechanical and thermal pain perception compared to control rats and also demonstrated increases in TNFα in the DRG, spinal cord dorsal horn, sciatic nerve and in the foot skin, 6 weeks after the onset of diabetes. Therapeutic approaches by HSV mediated expression of p55 TNF soluble receptor significantly attenuated the diabetes-induced hyperalgesia and decreased the expression of TNFα with reduction in the phosphorylation of p38MAPK in the spinal cord dorsal horn and DRG. The overall outcome of this study suggests that neuroinflammatory activation in the peripheral nervous system may be involved in the pathogenesis of painful neuropathy in Type 1 diabetes which can be alleviated by local expression of HSV vector expressing p55 TNF soluble receptor.

  20. Rikkunshito prevents paclitaxel-induced peripheral neuropathy through the suppression of the nuclear factor kappa B (NFκB) phosphorylation in spinal cord of mice

    PubMed Central

    Kamei, Junzo; Hayashi, Shunsuke; Sakai, Akane; Nakanishi, Yuki; Kai, Misa; Ikegami, Megumi; Ikeda, Hiroko

    2017-01-01

    Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB) in the spinal dorsal horn. Rikkunshito (RKT), a kampo medicine, increases the secretion of ghrelin in rodents and humans. Thus, RKT may attenuate paclitaxel-induced peripheral neuropathy by inhibiting phosphorylated NFκB (pNFκB) in the spinal cord. We found that paclitaxel dose-dependently induced mechanical hyperalgesia in mice. Paclitaxel increased the protein levels of spinal pNFκB, but not those of spinal NFκB. NFκB inhibitor attenuated paclitaxel-induced mechanical hyperalgesia suggesting that the activation of NFκB mediates paclitaxel-induced hyperalgesia. RKT dose-dependently attenuated paclitaxel-induced mechanical hyperalgesia. Ghrelin receptor antagonist reversed the RKT-induced attenuation of paclitaxel-induced mechanical hyperalgesia. RKT inhibited the paclitaxel-induced increase in the protein levels of spinal pNFκB. Taken together, the present study indicates that RKT exerts an antihyperalgesic effect in paclitaxel-induced neuropathic pain by suppressing the activation of spinal NFκB. PMID:28182729

  1. Antidisialosyl antibodies in chronic idiopathic ataxic neuropathy.

    PubMed

    Serrano-Munuera, C; Rojas-García, R; Gallardo, E; De Luna, N; Buenaventura, I; Ferrero, M; García, T; García-Merino, J A; González-Rodríguez, C; Guerriero, A; Marco, M; Márquez, C; Grau, J M; Graus, F; Illa, I

    2002-11-01

    Antidisialosyl antibodies were found in two out of 13 patients with chronic idiopathic ataxic neuropathy (CIAN) and not in 32 patients with different sensory neuropathies of known cause. This finding confirms the association of antidisialosyl antibodies and CIAN regardless of the absence of the M band. These antibodies may have pathogenic relevance; however, larger series are needed to establish their clinical significance.

  2. Hereditary deafness and sensory radicular neuropathy.

    PubMed

    Fitzpatrick, D B; Hooper, R E; Seife, B

    1976-09-01

    We report a case of radicular sensory neuropathy and deafness. The patients appears to be one of a family in whom several members were similarly afflicted. Thus, this case fits the pattern of hereditary deafness and sensory radicular neuropathy, originally described by Hicks in 1922.

  3. Extracorporeal shock wave therapy effectively prevented diabetic neuropathy

    PubMed Central

    Chen, Yi-Ling; Chen, Kuan-Hung; Yin, Tsung-Cheng; Huang, Tien-Hung; Yuen, Chun-Man; Chung, Sheng-Ying; Sung, Pei-Hsun; Tong, Meng-Shen; Chen, Chih-Hung; Chang, Hsueh-Wen; Lin, Kun-Chen; Ko, Sheung-Fat; Yip, Hon-Kan

    2015-01-01

    Background: We tested the hypothesis that extracorporeal shock wave (ECSW) therapy can effectively protect sciatic nerve (SN) from diabetes mellitus (DM)-induced neuropathy in leptin-deficient (ob/ob) mice. Methods and results: Eighteen-week C57BL/6 mice (n=8) served as age-matched controls (group 1) and ob/ob mice (n=16) were categorized into DM (group 2) and DM + ECSW (0.12 mJ/mm2 for 4 times of 200 impulses at 3-week intervals) (group 3). The animals were sacrificed two weeks post-ECSW. In vitro results showed that the protein expressions of oxidative stress (NOX-1, NOX-2, oxidized protein), inflammation (MMP-9, TNF-α, iNOS), apoptosis (Bax, cleaved caspase-3, & PARP), and DNA-damage marker (γ-H2AX) were significantly higher in RT4-D6P2T (schwannoma cell line) treated by menadione (25 µM) compared with control group and were significantly reversed after ECSW (0.12 mJ/mm2, 200 impulses) (all p<0.001). mRNA expressions of inflammation (MMP-9, TNF-α, iNOS), oxidative stress (NOX-1, NOX-2) and apoptosis (Bax, caspase-3) in SN were significantly higher in group 2 than in group 1 and were significantly reversed in group 3, whereas the mRNA expressions of anti-oxidants (HO-1, NQO1) progressively increased from group 1 to group 3 (all p<0.001). Cellular expressions of F4/80+, CD14+, γ-H2AX+ cells, and number of vacuolar formation in SN showed a pattern identical to that of inflammation markers among all groups (all p<0.001). Microscopic findings of Schwann cells and myelin-sheath scores, and number of eNOS+ cells in SN showed a reversed pattern compared to that of inflammation among all groups (all p<0.001). Conclusions: ECSW therapy protected SN against DM-induced neuropathy. PMID:26885256

  4. Pharmacological, behavioural and mechanistic analysis of HIV-1 gp120 induced painful neuropathy.

    PubMed

    Wallace, Victoria C J; Blackbeard, Julie; Pheby, Timothy; Segerdahl, Andrew R; Davies, Meirion; Hasnie, Fauzia; Hall, Susan; McMahon, Stephen B; Rice, Andrew S C

    2007-12-15

    A painful neuropathy is frequently observed in people living with human immunodeficiency virus type 1 (HIV-1). The HIV coat protein, glycoprotein 120 (gp120), implicated in the pathogenesis of neurological disorders associated with HIV, is capable of initiating neurotoxic cascades via an interaction with the CXCR4 and/or CCR5 chemokine receptors, which may underlie the pathogenesis of HIV-associated peripheral neuropathic pain. In order to elucidate the mechanisms underlying HIV-induced painful peripheral neuropathy, we have characterised pathological events in the peripheral and central nervous system following application of HIV-1 gp120 to the rat sciatic nerve. Perineural HIV-1 gp120 treatment induced a persistent mechanical hypersensitivity (44% decrease from baseline), but no alterations in sensitivity to thermal or cold stimuli, and thigmotactic (anxiety-like) behaviour in the open field. The mechanical hypersensitivity was sensitive to systemic treatment with gabapentin, morphine and the cannabinoid WIN 55,212-2, but not with amitriptyline. Immunohistochemical studies reveal: decreased intraepidermal nerve fibre density, macrophage infiltration into the peripheral nerve at the site of perineural HIV-1 gp120; changes in sensory neuron phenotype including expression of activating transcription factor 3 (ATF3) in 27% of cells, caspase-3 in 25% of cells, neuropeptide Y (NPY) in 12% of cells and galanin in 13% of cells and a spinal gliosis. These novel findings suggest that this model is not only useful for the elucidation of mechanisms underlying HIV-1-related peripheral neuropathy but may prove useful for preclinical assessment of drugs for the treatment of HIV-1 related peripheral neuropathic pain.

  5. Pharmacological, behavioural and mechanistic analysis of HIV-1 gp120 induced painful neuropathy

    PubMed Central

    Wallace, Victoria C.J.; Blackbeard, Julie; Pheby, Timothy; Segerdahl, Andrew R.; Davies, Meirion; Hasnie, Fauzia; Hall, Susan; McMahon, Stephen B.; Rice, Andrew S.C.

    2007-01-01

    A painful neuropathy is frequently observed in people living with human immunodeficiency virus type 1 (HIV-1). The HIV coat protein, glycoprotein 120 (gp120), implicated in the pathogenesis of neurological disorders associated with HIV, is capable of initiating neurotoxic cascades via an interaction with the CXCR4 and/or CCR5 chemokine receptors, which may underlie the pathogenesis of HIV-associated peripheral neuropathic pain. In order to elucidate the mechanisms underlying HIV-induced painful peripheral neuropathy, we have characterised pathological events in the peripheral and central nervous system following application of HIV-1 gp120 to the rat sciatic nerve. Perineural HIV-1 gp120 treatment induced a persistent mechanical hypersensitivity (44% decrease from baseline), but no alterations in sensitivity to thermal or cold stimuli, and thigmotactic (anxiety-like) behaviour in the open field. The mechanical hypersensitivity was sensitive to systemic treatment with gabapentin, morphine and the cannabinoid WIN 55,212-2, but not with amitriptyline. Immunohistochemical studies reveal: decreased intraepidermal nerve fibre density, macrophage infiltration into the peripheral nerve at the site of perineural HIV-1 gp120; changes in sensory neuron phenotype including expression of activating transcription factor 3 (ATF3) in 27% of cells, caspase-3 in 25% of cells, neuropeptide Y (NPY) in 12% of cells and galanin in 13% of cells and a spinal gliosis. These novel findings suggest that this model is not only useful for the elucidation of mechanisms underlying HIV-1-related peripheral neuropathy but may prove useful for preclinical assessment of drugs for the treatment of HIV-1 related peripheral neuropathic pain. PMID:17433546

  6. N-hexane neuropathy in offset printers.

    PubMed

    Chang, C M; Yu, C W; Fong, K Y; Leung, S Y; Tsin, T W; Yu, Y L; Cheung, T F; Chan, S Y

    1993-05-01

    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.

  7. Diabetic neuropathy and foot complications.

    PubMed

    Boulton, Andrew J M

    2014-01-01

    Foot ulceration and Charcot neuroarthropathy (CN) are well recognized and documented late sequelae of diabetic peripheral, somatic, and sympathetic autonomic neuropathy. The neuropathic foot, however, does not ulcerate spontaneously: it is a combination of loss of sensation due to neuropathy together with other factors such as foot deformity and external trauma that results in ulceration and indeed CN. The commonest trauma leading to foot ulcers in the neuropathic foot in Western countries is from inappropriate footwear. Much of the management of the insensate foot in diabetes has been learned from leprosy which similarly gives rise to insensitive foot ulceration. No expensive equipment is required to identify the high risk foot and recently developed tests such as the Ipswich Touch Test and the Vibratip have been shown to be useful in identifying the high risk foot. A comprehensive screening program, together with education of high risk patients, should help to reduce the all too high incidence of ulceration in diabetes. More recently another very high risk group has been identified, namely patients on dialysis, who are at extremely high risk of developing foot ulceration; this should be preventable. The most important feature in management of neuropathic foot ulceration is offloading as patients can easily walk on active foot ulcers due to the loss of pain sensation. Infection should be treated aggressively and if there is any evidence of peripheral vascular disease, arteriography and appropriate surgical management is also indicated. CN often presents with a unilateral hot, swollen foot and any patient presenting with these features known to have neuropathy should be treated as a Charcot until this is proven otherwise. Most important in the management of acute CN is offloading, often in a total contact cast.

  8. [Diagnosis of immune-mediated neuropathies].

    PubMed

    Diószeghy, Péter

    2011-09-25

    Separate discussion of immune-mediated neuropathies from other neuropathies is justified by the serious consequences of the natural course of these diseases, like disability and sometimes even life threatening conditions. On the other hand nowadays effective treatments already exist, and with timely and correct diagnosis an appropriately chosen treatment may result in significant improvement of quality of life, occasionally even complete recovery. These are rare diseases, and the increasing number of different variants makes it more difficult to recognize them. Their diagnosis is based on the precise knowledge of clinical signs and symptoms, and it is verified by the help of neurophysiologic and laboratory, first of all CSF examinations. Description of clinical features of the classic acute immune-mediated neuropathy, characterized by ascending paresis and demyelination is followed by a summary of characteristics of newly recognized axonal, regional and functional variants. Chronic immune-mediated demyelinating polyneuropathies are not diagnosed in due number even today. This paper does not only present the classic form but it also introduces the ever increasing special variants, like distal acquired demyelinating sensory neuropathy, Lewis-Sumner syndrome, multifocal motor neuropathy and paraproteinemic neuropathies. Vasculitic neuropathies can be divided into two groups: systemic and non-systemic ones. The first sign of a vasculitic neuropathy is a progressive, painful mononeuropathy; the classic clinical presentation is the mononeuritis multiplex. It is characterized by general signs like fever, loss of weight, fatigue. In systemic vasculitis organ specific symptoms are also present. From the paraneoplastic diseases the subacute sensory neuropathy and the sensory neuronopathy are members of the immune-mediated neuropathies, being most frequently associated with small cell lung cancer.

  9. Changes in contralateral protein metabolism following unilateral sciatic nerve section

    SciTech Connect

    Menendez, J.A.; Cubas, S.C.

    1990-03-01

    Changes in nerve biochemistry, anatomy, and function following injuries to the contralateral nerve have been repeatedly reported, though their significance is unknown. The most likely mechanisms for their development are either substances carried by axoplasmic flow or electrically transmitted signals. This study analyzes which mechanism underlies the development of a contralateral change in protein metabolism. The incorporation of labelled amino acids (AA) into proteins of both sciatic nerves was assessed by liquid scintillation after an unilateral section. AA were offered locally for 30 min to the distal stump of the sectioned nerves and at homologous levels of the intact contralateral nerves. At various times, from 1 to 24 h, both sciatic nerves were removed and the proteins extracted with trichloroacetic acid (TCA). An increase in incorporation was found in both nerves 14-24 h after section. No difference existed between sectioned and intact nerves, which is consistent with the contralateral effect. Lidocaine, but not colchicine, when applied previously to the nerves midway between the sectioning site and the spinal cord, inhibited the contralateral increase in AA incorporation. It is concluded that electrical signals, crossing through the spinal cord, are responsible for the development of the contralateral effect. Both the nature of the proteins and the significance of the contralateral effect are matters for speculation.

  10. Bone Marrow-Derived Mesenchymal Stem Cells Improve Diabetic Neuropathy by Direct Modulation of Both Angiogenesis and Myelination in Peripheral Nerves.

    PubMed

    Han, Ji Woong; Choi, Dabin; Lee, Min Young; Huh, Yang Hoon; Yoon, Young-sup

    2016-01-01

    Recent evidence has suggested that diabetic neuropathy (DN) is pathophysiologically related to both impaired angiogenesis and a deficiency of neurotrophic factors in the nerves. It is widely known that vascular and neural growths are intimately associated. Mesenchymal stem cells (MSCs) promote angiogenesis in ischemic diseases and have neuroprotective effects, particularly on Schwann cells. Accordingly, we investigated whether DN could be improved by local transplantation of MSCs by augmenting angiogenesis and neural regeneration such as remyelination. In sciatic nerves of streptozotocin (STZ)-induced diabetic rats, motor and sensory nerve conduction velocities (NCVs) and capillary density were reduced, and axonal atrophy and demyelination were observed. After injection of bone marrow-derived MSCs (BM-MSCs) into hindlimb muscles, NCVs were restored to near-normal levels. Histological examination demonstrated that injected MSCs were preferentially and durably engrafted in the sciatic nerves, and a portion of the engrafted MSCs were distinctively localized close to vasa nervora of sciatic nerves. Furthermore, vasa nervora increased in density, and the ultrastructure of myelinated fibers in nerves was observed to be restored. Real-time RT-PCR experiments showed that gene expression of multiple factors involved in angiogenesis, neural function, and myelination were increased in the MSC-injected nerves. These findings suggest that MSC transplantation improved DN through direct peripheral nerve angiogenesis, neurotrophic effects, and restoration of myelination.

  11. Hereditary neuralgic amyotrophy associated with a relapsing multifocal sensory neuropathy.

    PubMed Central

    Thomas, P K; Ormerod, I E

    1993-01-01

    A family with neuralgic amyotrophy (idiopathic brachial plexus neuropathy) associated with a multifocal sensory neuropathy is described. Four members over two generations were affected by neuralgic amyotrophy, inherited as an apparent autosomal dominant trait; two also had a multifocal relapsing sensory neuropathy with the clinical features of Wartenberg's migrant neuropathy. PMID:8429311

  12. Traumatic Optic Neuropathy: A Review

    PubMed Central

    Kumaran, Arjunan Muthu; Sundar, Gangadhara; Chye, Lim Thiam

    2014-01-01

    The aim of this article is to evaluate current literature on investigation and management of traumatic optic neuropathy (TON), propose recommendations for diagnosis and management, and explore novel future treatments. TON, though uncommon, causes substantial visual loss. Without clear guidelines, there is much ambiguity regarding its diagnosis and management. Investigation and treatment (conservative, medical, surgical, and combined) vary widely between centers. Electronic databases PubMed, MEDLINE, PROSPERO, CENTRAL, and EMBASE were searched for content that matched “Traumatic optic neuropathy.” Articles with abstracts and full text available, published in the past 10 years, written English and limited to human adults, were selected. All study designs were acceptable except case reports and case series with fewer 10 patients. All abstracts were then evaluated for relevance. References of these studies were evaluated and if also relevant, included. A total of 2,686 articles were retrieved and 43 examined for relevance. Of these, 23 articles were included. TON is a clinical diagnosis. Visual-evoked potential is useful in diagnosis and prognosis. Computed tomography demonstrates canal fractures and concomitant injuries. Magnetic resonance images should be reserved for select and stable patients. Conservative treatment is appropriate in mild TON. Steroids are of questionable benefit and may be harmful. Surgery should be reserved for patients with radiological evidence of compression and individualized. PMID:25709751

  13. Metronidazole: newly recognized cause of autonomic neuropathy.

    PubMed

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

    2006-05-01

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

  14. Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy

    PubMed Central

    Khadilkar, Satish V.; Deshmukh, Shrikant S.; Dhonde, Pramod D.

    2011-01-01

    The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP). Pure motor (multifocal motor neuropathy), sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy), exclusively distal sensory (distal acquired demyelinating sensory neuropathy) and very proximal sensory (chronic immune sensory polyradiculopathy) constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc.) have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies. PMID:21808468

  15. Immediate versus delayed primary nerve repair in the rabbit sciatic nerve

    PubMed Central

    Piskin, Ahmet; Altunkaynak, Berrin Zühal; Çιtlak, Atilla; Sezgin, Hicabi; Yazιcι, Ozgür; Kaplan, Süleyman

    2013-01-01

    It is well known that peripheral nerve injury should be treated immediately in the clinic, but in some instances, repair can be delayed. This study investigated the effects of immediate versus delayed (3 days after injury) neurorrhaphy on repair of transected sciatic nerve in New Zealand rabbits using stereological, histomorphological and biomechanical methods. At 8 weeks after immediate and delayed neurorrhaphy, axon number and area in the sciatic nerve, myelin sheath and epineurium thickness, Schwann cell morphology, and the mechanical property of nerve fibers did not differ obviously. These results indicate that delayed neurorrhaphy do not produce any deleterious effect on sciatic nerve repair. PMID:25206663

  16. Amiodarone-Associated Optic Neuropathy: Clinical Review.

    PubMed

    Wang, An-Guor; Cheng, Hui-Chen

    2017-04-01

    Amiodarone, an antiarrhythmic agent, has been associated with visual loss secondary to optic neuropathy. The reported mean duration of amiodarone use before visual loss is about 9 months. Patients receiving amiodarone have a 2-fold increased risk of developing optic neuropathy, especially in males and possibly in patients with longer duration of treatment. Amiodarone-associated optic neuropathy is characterised by an insidious onset, slow progression, bilateral simultaneous visual loss, and protracted disc swelling. After discontinuing amiodarone use, visual acuity and visual field deficits tend to improve or stabilise in most patients, with about 20% of the patients getting worse.

  17. Compressive neuropathy in the upper limb

    PubMed Central

    Thatte, Mukund R.; Mansukhani, Khushnuma A.

    2011-01-01

    Entrampment neuropathy or compression neuropathy is a fairly common problem in the upper limb. Carpal tunnel syndrome is the commonest, followed by Cubital tunnel compression or Ulnar Neuropathy at Elbow. There are rarer entities like supinator syndrome and pronator syndrome affecting the Radial and Median nerves respectively. This article seeks to review comprehensively the pathophysiology, Anatomy and treatment of these conditions in a way that is intended for the practicing Hand Surgeon as well as postgraduates in training. It is generally a rewarding exercise to treat these conditions because they generally do well after corrective surgery. Diagnostic guidelines, treatment protocols and surgical technique has been discussed. PMID:22022039

  18. 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.

  19. [Microcirculatory bed of the injured sciatic nerve (experimental study)].

    PubMed

    Chaĭkovskiĭ, Iu B

    1982-10-01

    A morphometric, histochemical and electron microscopic investigation of the sciatic nerve hemomicrocirculatory bed was performed (on 45 dogs) after its small part had been resected and the cut end had been sutured microsurgically. During 2--4 weeks after the operation the microvessel reactions depend mainly on the trauma and the resulted processes of aseptic inflammation, the neural fibre degeneration and vascular denervation. Within the interval of 2--4 weeks up to 6-12 months after the nerve cutting, transformations in the hemomicrocirculatory bed play an important role in the energy and plastic ensurance of the regenerative neuroma elements and the adjoining parts of the nerve. Specific reactions of the peripheral nerve microvessels at their restoration should be taken into account when estimating time of surgical operations for neural trunks and elaborating some new neurosurgical approaches.

  20. [Compression of the sciatic nerve in uremic tumor calcinosis].

    PubMed

    García, S; Cofán, F; Combalia, A; Casas, A; Campistol, J M; Oppenheimer, F

    1999-02-01

    Tumoral calcinosis is an uncommon and benign condition characterized by the presence of slow-growing calcified periarticular soft tissue masses of varying size. They are usually asymptomatic and nerve compression is rare. We describe the case of a 54-year-old female patient on long-term hemodialysis for chronic renal failure presenting sciatica in the left lower limb secondary to an extensive uremic tumoral calcinosis that affected the hip and thigh. The pathogenesis of uremic tumoral calcinosis as well as the treatment and clinical outcome are analyzed. The uncommon nerve compression due to tumoral calcinosis are reviewed. In conclusion, uremic tumoral calcinosis is a not previously reported infrequent cause of sciatic nerve compression.

  1. Updates in diabetic peripheral neuropathy.

    PubMed

    Juster-Switlyk, Kelsey; Smith, A Gordon

    2016-01-01

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

  2. Updates in diabetic peripheral neuropathy

    PubMed Central

    Juster-Switlyk, Kelsey; Smith, A. Gordon

    2016-01-01

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

  3. Effects of 660- and 980-nm low-level laser therapy on neuropathic pain relief following chronic constriction injury in rat sciatic nerve.

    PubMed

    Masoumipoor, M; Jameie, S B; Janzadeh, A; Nasirinezhad, F; Soleimani, M; Kerdary, M

    2014-09-01

    Neuropathic pain (NP) is one of the most suffered conditions in medical disciplines. The role of reactive oxygen species (ROS) and oxidative stress in the induction of NP was studied by many researchers. Neuropathies lead to medical, social, and economic isolation of the patient, so various therapies were used to treat or reduce it. During the recent years, low-level laser therapy (LLLT) has been used in certain areas of medicine and rehabilitation. Chronic constriction injury (CCI) is a well-known model for neuropathic pain studies. In order to find the effects of different wavelengths of LLLT on the injured sciatic nerve, the present research was done. Thirty Wistar adult male rats (230-320 g) were used in this study. The animals were randomly divided into three groups (n = 10). To induce neuropathic pain for the sciatic nerve, the CCI technique was used. Low-level laser of 660 and 980 nm was used for two consecutive weeks. Thermal and mechanical hyperalgesia was done before and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. CCI decreased the pain threshold, whereas both wavelengths of LLLT for 2 weeks increased mechanical and thermal threshold significantly. A comparison of the mechanical and thermal threshold showed a significant difference between the therapeutic effects of the two groups that received LLLT. Based on our findings, the laser with a 660-nm wavelength had better therapeutic effects than the laser with a 980-nm wavelength, so the former one may be used for clinical application in neuropathic cases; however, it needs more future studies.

  4. [Post-traumatic infraorbital nerve neuropathy].

    PubMed

    Sakavicius, Dalius; Kubilius, Ricardas; Sabalys, Gintautas

    2002-01-01

    The authors have investigated functional state of infraorbital nerve of 479 patients with zygomatic fractures. The degree of nerve damage was evaluated according to changes of pain threshold during damaged nerve stimulation. It was estimated that in 64.3% of zygomatic fractures the infraorbital nerve was affected. The nerve damage degree could be mild, moderate and severe. In 43.18% of moderate and severe nerve damage cases the neuropathy develops. The symptoms, signs and treatment of neuropathy have been described. The neuropathy with clinical symptoms as permanent soreness and paresthesias (itch, "running ant", fibrillations of cheek tissues etc.) in the infraorbital nerve innervation zone occur to 43.18% of the patients after moderate and severe damage of the nerve. The treatment of neuropathy was analysed. In cases of moderate and severe nerve damages, authors recommend to perform decompression of the nerve, because if not applied, the function of nerve does not recover.

  5. INHERITED NEUROPATHIES: CLINICAL OVERVIEW AND UPDATE

    PubMed Central

    KLEIN, CHRISTOPHER J.; DUAN, XIAOHUI; SHY, MICHAEL E.

    2014-01-01

    Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. PMID:23801417

  6. APOE gene polymorphisms and diabetic peripheral neuropathy.

    PubMed

    Monastiriotis, Christodoulos; Papanas, Nikolaos; Veletza, Stavroula; Maltezos, Efstratios

    2012-09-08

    Genetic factors may influence the natural course of diabetic peripheral neuropathy and explain some of its variability. The aim of this review was to examine the association between apolipoprotein E (apoE) gene polymorphisms and diabetic peripheral neuropathy. Four relevant studies were identified. The two earlier works provided evidence that the ɛ4 allele is a risk factor for this complication, while the two more recent studies were negative. Important differences in the methodology used and in the populations included are obvious, rendering difficult the comparison between studies. In conclusion, the association between APOE gene polymorphisms and diabetic peripheral neuropathy is still unclear. Available evidence is rather limited and results have so far been contradictory. Future studies should employ more robust methodology, adjusting for potential confounders and for the prevalence of neuropathy in the general population with diabetes.

  7. Acquired versus familial demyelinative neuropathies in children.

    PubMed

    Miller, R G; Gutmann, L; Lewis, R A; Sumner, A J

    1985-01-01

    The electrophysiologic differences between chronic acquired demyelinative neuropathy and the demyelinative form of Charcot-Marie-Tooth disease have recently been reported. The present report extends these observations to include the genetically determined demyelinating neuropathies seen in metachromatic leukodystrophy, Krabbe's leukodystrophy, and Cockayne's syndrome. The electrophysiologic features of metachromatic leukodystrophy (five patients), Krabbe's (four patients), and Cockayne's syndrome (three patients) were all similar. There was uniform slowing of conduction (both in different nerves and in different nerve segments), and conduction block was not seen. These findings are consistent with a uniform degree of demyelination in multiple nerves and throughout the entire length of individual axons. Thus, uniform slowing of nerve conduction constitutes strong evidence for a familial demyelinative neuropathy, as opposed to the multifocal slowing seen in acute and chronic acquired demyelinative neuropathy.

  8. Bioactive Fraction of Annona reticulata Bark (or) Ziziphus jujuba Root Bark along with Insulin Attenuates Painful Diabetic Neuropathy through Inhibiting NF-κB Inflammatory Cascade

    PubMed Central

    Kandimalla, Raghuram; Dash, Suvakanta; Kalita, Sanjeeb; Choudhury, Bhaswati; Malampati, Sandeep; Devi, Rajlakshmi; Ramanathan, Muthiah; Talukdar, Narayan C.; Kotoky, Jibon

    2017-01-01

    The present study explains the neuroprotective ability of bioactive fractions of Annona reticulata bark (ARB) and Ziziphus jujuba root bark (ZJ) along with insulin against diabetic neuropathy. By using different solvents of increasing polarity ARB and ZJ were undergone for bioactive guided fractionation. The neuroprotective ability of the all the plant fractions were tested against H2O2 induced toxicity in SHSY5Y neuroblastoma cell lines and DRG neuronal cells. Among all the fractions tested, the methanol extract of ARB and ZJ (ARBME and ZJME) and its water fractions (ARBWF and ZJWF) exhibited significant neuroprotection against H2O2 induced toxicity in SHSY5Y cells and DRG neuronal cells. Further both the active fractions were tested against streptozotocin (55 mg/kg i.p.) induced diabetic neuropathy in male Wistar rats. Body weight changes, blood glucose levels and pain threshold through hot plate, tail immersion, cold plate and Randall-Sillitto methods were measured throughout the study at weekly interval. After completion of the drug treatment period, all the animals were sacrificed to measure the sciatic nerve lipid peroxidation, antioxidative enzyme levels (SOD, catalase, and GSH) and cytokine levels (IL-1β, IL-6, IL-10, TNF-α, iNOS, and NFκB) through ELISA and western blotting analysis. Results of this study explain that ARBME, ZJME, ARBWF, and ZJWF along with insulin potentially attenuate the thermal, mechanical hyperalgesia and cold allodynia in diabetic neuropathic rats, where insulin treatment alone failed to diminish the same. Reduction of sciatic nerve oxidative stress, NF-κB and iNOS mediated inflammatory cascade and normalization of abnormal cytokine release confirms the possible mechanism of action. The present study confirms the neuroprotective ability of ARB and ZJ against painful diabetic neuropathy through inhibiting oxidative stress and NF-κB inflammatory cascade. PMID:28381989

  9. 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

  10. Bioactive Fraction of Annona reticulata Bark (or) Ziziphus jujuba Root Bark along with Insulin Attenuates Painful Diabetic Neuropathy through Inhibiting NF-κB Inflammatory Cascade.

    PubMed

    Kandimalla, Raghuram; Dash, Suvakanta; Kalita, Sanjeeb; Choudhury, Bhaswati; Malampati, Sandeep; Devi, Rajlakshmi; Ramanathan, Muthiah; Talukdar, Narayan C; Kotoky, Jibon

    2017-01-01

    The present study explains the neuroprotective ability of bioactive fractions of Annona reticulata bark (ARB) and Ziziphus jujuba root bark (ZJ) along with insulin against diabetic neuropathy. By using different solvents of increasing polarity ARB and ZJ were undergone for bioactive guided fractionation. The neuroprotective ability of the all the plant fractions were tested against H2O2 induced toxicity in SHSY5Y neuroblastoma cell lines and DRG neuronal cells. Among all the fractions tested, the methanol extract of ARB and ZJ (ARBME and ZJME) and its water fractions (ARBWF and ZJWF) exhibited significant neuroprotection against H2O2 induced toxicity in SHSY5Y cells and DRG neuronal cells. Further both the active fractions were tested against streptozotocin (55 mg/kg i.p.) induced diabetic neuropathy in male Wistar rats. Body weight changes, blood glucose levels and pain threshold through hot plate, tail immersion, cold plate and Randall-Sillitto methods were measured throughout the study at weekly interval. After completion of the drug treatment period, all the animals were sacrificed to measure the sciatic nerve lipid peroxidation, antioxidative enzyme levels (SOD, catalase, and GSH) and cytokine levels (IL-1β, IL-6, IL-10, TNF-α, iNOS, and NFκB) through ELISA and western blotting analysis. Results of this study explain that ARBME, ZJME, ARBWF, and ZJWF along with insulin potentially attenuate the thermal, mechanical hyperalgesia and cold allodynia in diabetic neuropathic rats, where insulin treatment alone failed to diminish the same. Reduction of sciatic nerve oxidative stress, NF-κB and iNOS mediated inflammatory cascade and normalization of abnormal cytokine release confirms the possible mechanism of action. The present study confirms the neuroprotective ability of ARB and ZJ against painful diabetic neuropathy through inhibiting oxidative stress and NF-κB inflammatory cascade.

  11. Endoscopic Sciatic Nerve Decompression in the Prone Position-An Ischial-Based Approach.

    PubMed

    Jackson, Timothy J

    2016-06-01

    Deep gluteal syndrome is described as sciatic nerve entrapment in the region deep to the gluteus maximus muscle. The entrapment can occur from the piriformis muscle, fibrous bands, blood vessels, and hamstrings. Good clinical outcomes have been shown in patients treated by open and endoscopic means. Sciatic nerve decompression with or without piriformis release provides a surgical solution to a difficult diagnostic and therapeutic problem. Previous techniques have used open methods that can now performed endoscopically. The technique of an endoscopic approach to sciatic nerve decompression in the prone position is described as well as its advantages and common findings. Through this ischial-based approach, a familiar anatomy is seen and areas of sciatic nerve entrapment can be readily identified and safely decompressed.

  12. Unique formation of sciatic nerve below the piriformis muscle - a case report.

    PubMed

    Patil, Jyothsna; Swamy, Ravindra S; Rao, Mohandas K G; Kumar, Naveen; Somayaji, S N

    2014-01-01

    Dorsal and ventral divisions of ventral rami of lower lumbar and sacral spinal nerve were found to pass ventral and dorsal to the piriformis muscle respectively. These divisions joined each other below the piriformis muscle to form sciatic nerve. This low formation of sciatic nerve was observed in distal part of left gluteal region of a 50-year-old male cadaver. The sciatic nerve thus formed passed caudally into back of thigh and divided into tibial and common peroneal nerves in the upper part of popliteal fossa. In addition, a communicating nerve from the sciatic nerve was found to join the common peroneal nerve in the popliteal fossa. Such variations may lead to piriformis syndrome or non-discogenic sciatica.

  13. Bilateral Persistent Sciatic Artery Aneurysm Discovered by Atypical Sciatica: A Case Report

    SciTech Connect

    Mazet, Nathalie; Soulier-Guerin, Karine; Ruivard, Marc; Garcier, Jean-Marc; Boyer, Louis

    2006-12-15

    We report a case of a bilateral persistent sciatic artery aneurysm, diagnosed by atypical sciatica on computed tomography and magnetic resonance imaging. The different variants, the revealing features, and possible treatment are discussed.

  14. Pattern Recognition Approach to Neuropathy and Neuronopathy

    PubMed Central

    Barohn, Richard J; Amato, Anthony A.

    2014-01-01

    Synopsis Neuropathic disorders encompass those that affect the neuron’s cell body or neuronopathies, those affecting the peripheral process, or peripheral neuropathies. The peripheral neuropathies can be broadly subdivided into the myelinopathies and axonopathies. These conditions can be hereditary or acquired. Each of these disorders has distinct clinical features that enable neurologists to recognize the various patterns of presentation. Once a particular pattern is established, further laboratory studies can be performed to confirm the clinical impression. PMID:23642713

  15. Diabetic neuropathy, A review of clinical manifestations.

    PubMed

    Lawrence, A M; Abraira, C

    1976-01-01

    Diabetic neuropathy in some form or other afflicts a majority of patients with diabetes mellitus. Neuropathic disturbance of sensory, motor or autonomic nerves may occur singly or in combination. Cranial nerve and other mononeuropathies generally resolve spontaneously. Autonomic neuropathy which can result in orthostatic hypotension, gastroparesis diabeticorum, nocturnal diarrhea, atonic bladder and impotence, although chronic, may wax and wane in clinical severity. Neuritis, disesthesias and painful sensory neuritis may resolve with good diabetic control; on occasion, diphenylhydantoin has been of therapeutic benefit.

  16. Treatment of immune-mediated, dysimmune neuropathies.

    PubMed

    Finsterer, J

    2005-08-01

    This review focuses on the actual status and recent advances in the treatment of immune-mediated neuropathies, including: Guillain-Barre syndrome (GBS) with its subtypes acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, Miller Fisher syndrome, and acute pandysautonomia; chronic inflammatory demyelinating polyneuropathy (CIDP) with its subtypes classical CIDP, CIDP with diabetes, CIDP/monoclonal gammopathy of undetermined significance (MGUS), sensory CIDP, multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy or Lewis-Sumner syndrome, multifocal acquired sensory and motor neuropathy, and distal acquired demyelinating sensory neuropathy; IgM monoclonal gammopathies with its subtypes Waldenstrom's macroglobulinemia, myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome, mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome, and MGUS. Concerning the treatment of GBS, there is no significant difference between intravenous immunoglobulins (IVIG), plasma exchange or plasma exchange followed by IVIG. Because of convenience and absent invasiveness, IVIG are usually preferred. In treating CIDP corticosteroids, IVIG, or plasma exchange are equally effective. Despite the high costs and relative lack of availability, IVIG are preferentially used. For the one-third of patients, who does not respond, other immunosuppressive options are available. In MMN IVIG are the treatment of choice. Inadequate response in 20% of the patients requires adjunctive immunosuppressive therapies. Neuropathies with IgM monoclonal gammopathy may respond to various chemotherapeutic agents, although the long-term effects are unknown. In addition, such treatment may be associated with serious side effects. Recent data support the use of rituximab, a monoclonal antibody against the B

  17. [Chronic inflammatory demyelinating neuropathies and their variants

    PubMed

    Vallat, J.-M.; Tabaraud, F.; Magy, L.; Macian, F.

    2002-12-01

    The Chronic Inflammatory Demyelinating Polyradiculoneuropathies (CIDP) constitute a syndrome whose incidence is difficult to evaluate, and is probably underestimated. In the course of this presentation, we deliberately restricted discussion to issues raised in recent years concerning the extent of this syndrome. We discuss diagnostic criteria, especially electrophysiological ones. As the criteria proposed by the ad hoc committee of the American Academy of Neurology in 1991 have been questioned due to lack of sensitivity, new ones have been proposed recently. We briefly discuss the different types of chronic dysimmune demyelinating neuropathy: not only the CIDP, but also the Lewis and Sumner syndrome or multifocal inflammatory demyelinating neuropathy and the multiple conduction block neuropathies. At last, we point out the consistent finding of axonal involvement in the course of a chronic demyelinating neuropathy; over time, it can become predominant, which may make diagnosis difficult by suggesting a chronic axonal neuropathy that may be assumed to be primary. Consideration of these points may help clinicians recognize more chronic dysimmune neuropathies, for which immunosuppressive therapy has been found to be effective.

  18. Effects of sciatic nerve stimulation on the propagation of cortical spreading depression

    NASA Astrophysics Data System (ADS)

    Sun, Xiaoli; Yu, Zhidong; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng

    2008-02-01

    Cortical spreading depression (CSD) is an important pathological model of migraine and is related to other neural disorders, such as cerebral ischemia and epilepsy. It has been reported that brain stimulation is a quite effective way to treat neural diseases. However, direct stimulation could cause harm to brain. If peripheral nerve stimulation could have the same treatment, it would be essential to investigate the mechanisms of peripheral nerve and the study of sciatic nerve stimulation would have profound clinical meaning. In this paper, we used optical intrinsic signal imaging (OISI) and extracellular electrophysiologic recording techniques to study the effects of sciatic nerve stimulation on the propagation of CSD. We found that: (1) continuous sciatic nerve stimulation on rats caused a decrease in light intensity on the whole cortex, which meant an increase in cerebral blood volume(CBV); (2) the spreading velocity of CSD declined from 3.63+/- 0.272 mm/min to 3.06+/-0.260 mm/min during sciatic nerve stimulation, compared with that without sciatic nerve stimulation. In summary, data suggests that sciatic nerve stimulation elicits a response of cortex and causes a slowdown in the propagation of CSD.

  19. Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes.

    PubMed

    Negi, Geeta; Kumar, Ashutosh; Sharma, Shyam S

    2011-11-01

    High glucose driven reactive oxygen intermediates production and inflammatory damage are recognized contributors of nerve dysfunction and subsequent damage in diabetic neuropathy. Sulforaphane, a known chemotherapeutic agent holds a promise for diabetic neuropathy because of its dual antioxidant and anti-inflammatory activities. The present study investigated the effect of sulforaphane in streptozotocin (STZ) induced diabetic neuropathy in rats. For in vitro experiments neuro2a cells were incubated with sulforaphane in the presence of normal (5.5 mM) and high glucose (30 mM). For in vivo studies, sulforaphane (0.5 and 1 mg/kg) was administered six weeks post diabetes induction for two weeks. Motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and pain behavior were improved and malondialdehyde (MDA) level was reduced by sulforaphane. Antioxidant effect of sulforaphane is derived from nuclear erythroid 2-related factor 2 (Nrf2) activation as demonstrated by increased expression of Nrf2 and downstream targets hemeoxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1) in neuro2a cells and sciatic nerve of diabetic animals. Nuclear factor-kappa B (NF-κB) inhibition seemed to be responsible for antiinflammatory activity of sulforaphane as there was reduction in NF-κB expression and IκB kinase (IKK) phosphorylation along with abrogation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6) levels. Here in this study we provide an evidence that sulforaphane is effective in reversing the various deficits in experimental diabetic neuropathy. This study supports the defensive role of Nrf2 in neurons under conditions of oxidative stress and also suggests that the NF-κB pathway is an important modulator of inflammatory damage in diabetic neuropathy.

  20. Peripheral neuropathy in subclinical hypothyroidism.

    PubMed

    Misiunas, A; Niepomniszcze, H; Ravera, B; Faraj, G; Faure, E

    1995-08-01

    Alterations in peripheral nerves are well documented in overt myxedema but not in subclinical hypothyroidism. We performed electrophysiologic studies to investigate such abnormalities in patients with normal serum total T4 and hyperresponsiveness of TSH to TRH, either with normal or high levels of basal circulating TSH. Subjects were divided in three groups: (i) Hypothyroidism Stage I (group () (n = 17, mean age = 39 +/- 34 years), T4 = 9 +/- 0.7 micrograms/dL, TSH = 4.3 +/- 0.4 microU/mL, sTSH post-TRH (peak value) = 37.6 +/- 1.6 microU/mL; (ii) Hypothyroidism Stage II (group II) (n = 10, mean age: 43 +/- 6 years), T4 = 7.7 +/- 0.8 microgram/dL, TSH = 20 +/- 5 microU/mL, TSH post-TRH > 50 microU/mL; (iii) Control Group (n = 20, mean age 41 +/- 5 years), healthy subjects. All patients and controls were women. TRH test consisted in the i.v. injection of 200 micrograms TRH (normal peak value up to 25 microU/mL, normal basal TSH < 5.5 microU/mL. None of the patients had carpal tunnel syndrome or any other neurological or metabolic disturbances. We studied the distal motor latencies, motor and sensory amplitudes, and nerve conduction velocities. The motor parameters were measured in the median and external sciatic popliteal (ESP) nerves, and the sensory parameters in the median and sural nerves. In most cases values were obtained from both right and left nerves. Motor parameters: no differences were found between all groups for conduction velocities (CV).(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Peripheral neuropathy associated with mitochondrial disease in children.

    PubMed

    Menezes, Manoj P; Ouvrier, Robert A

    2012-05-01

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

  2. A refined technique for sciatic denervation in a golden-mantled ground squirrel (Callospermophilus lateralis) model of disuse atrophy.

    PubMed

    Sarukhanov, Valeri; Van Andel, Roger; Treat, Michael D; Utz, Jenifer C; van Breukelen, Frank

    2014-06-01

    Disuse atrophy of both muscle and bone can occur rapidly during periods of inactivity. In several rodent models developed for the study of disuse atrophy, immobilization is induced by prolonged cage restraint, hind limb unloading, tenotomy, sciatic nerve block or sciatic denervation. In less tractable species such as wild-caught hibernating rodents, the sciatic denervation model is superior in terms of both animal welfare and applicability to the characteristics of natural cases of disuse atrophy. The authors describe a refined surgical approach to sciatic denervation in golden-mantled ground squirrels (Callospermophilus lateralis), a hibernating species, that improves animal welfare and reduces the incidence of post-operative complications such as autotomy.

  3. Metanx Alleviates Multiple Manifestations of Peripheral Neuropathy and Increases Intraepidermal Nerve Fiber Density in Zucker Diabetic Fatty Rats

    PubMed Central

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

    2012-01-01

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

  4. 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

  5. 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

    2016-09-08

    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.

  6. Elevated protein carbonylation, and misfolding in sciatic nerve from db/db and Sod1(-/-) mice: plausible link between oxidative stress and demyelination.

    PubMed

    Hamilton, Ryan T; Bhattacharya, Arunabh; Walsh, Michael E; Shi, Yun; Wei, Rochelle; Zhang, Yiqiang; Rodriguez, Karl A; Buffenstein, Rochelle; Chaudhuri, Asish R; Van Remmen, Holly

    2013-01-01

    Diabetic peripheral polyneuropathy is associated with decrements in motor/sensory neuron myelination, nerve conduction and muscle function; however, the mechanisms of reduced myelination in diabetes are poorly understood. Chronic elevation of oxidative stress may be one of the potential determinants for demyelination as lipids and proteins are important structural constituents of myelin and highly susceptible to oxidation. The goal of the current study was to determine whether there is a link between protein oxidation/misfolding and demyelination. We chose two distinct models to test our hypothesis: 1) the leptin receptor deficient mouse (dbdb) model of diabetic polyneuropathy and 2) superoxide dismutase 1 knockout (Sod1(-/-) ) mouse model of in vivo oxidative stress. Both experimental models displayed a significant decrement in nerve conduction, increase in tail distal motor latency as well as reduced myelin thickness and fiber/axon diameter. Further biochemical studies demonstrated that oxidative stress is likely to be a potential key player in the demyelination process as both models exhibited significant elevation in protein carbonylation and alterations in protein conformation. Since peripheral myelin protein 22 (PMP22) is a key component of myelin sheath and has been found mutated and aggregated in several peripheral neuropathies, we predicted that an increase in carbonylation and aggregation of PMP22 may be associated with demyelination in dbdb mice. Indeed, PMP22 was found to be carbonylated and aggregated in sciatic nerves of dbdb mice. Sequence-driven hydropathy plot analysis and in vitro oxidation-induced aggregation of purified PMP22 protein supported the premise for oxidation-dependent aggregation of PMP22 in dbdb mice. Collectively, these data strongly suggest for the first time that oxidation-mediated protein misfolding and aggregation of key myelin proteins may be linked to demyelination and reduced nerve conduction in peripheral neuropathies.

  7. Genetics Home Reference: autosomal recessive axonal neuropathy with neuromyotonia

    MedlinePlus

    ... with neuromyotonia is a rare form of inherited peripheral neuropathy. This group of conditions affects an estimated 1 ... Page National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy Fact Sheet Educational Resources (2 links) Merck Manual ...

  8. Burn-related peripheral neuropathy: A systematic review.

    PubMed

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

    2017-03-24

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

  9. Genetics Home Reference: neuropathy, ataxia, and retinitis pigmentosa

    MedlinePlus

    ... Genetics Home Health Conditions NARP neuropathy, ataxia, and retinitis pigmentosa Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Neuropathy, ataxia, and retinitis pigmentosa ( NARP ) is a condition that causes a variety ...

  10. [Antiglycolipid antibody in inflammatory neuropathy].

    PubMed

    Kusunoki, S

    1995-12-01

    Antiglycolipid antibody is frequently detected in the acute phase sera from patients with acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome, GBS). The titer is highest in the serum sample taken first after the neurological onset, and decreases with clinical improvement. Antiglycolipid antibody may play a role in the pathogenetic mechanism of GBS. GM1 and GD1b are the antigens most commonly recognized. Monoclonal anti-GD1b antibody specifically bound to the paranodal myelin of the peripheral nervous system. Serum anti-GD1b antibody may cause demyelinative neuropathy by binding to the paranodal myelin of the peripheral nervous system. Anti-GQ1b IgG antibody is specifically raised in almost all the sera from Fisher syndrome and GBS with ophthalmoplegia. Anti-GQ1b monoclonal antibody immunostained specifically the paranodal myelin of the extramedullary portion of oculomotor, trochlear and abducens nerves, but no such staining was observed in the other peripheral nerves. Anti-GQ1b antibody may cause conduction block in the cranial nerves innervating the muscles for extraocular movement by binding to the paranodal myelin of those nerves. Anti-GalNAc-GD1a antibody is detected in the patients with GBS with very low or inexcitable compound muscle action potentials. The sera from patients with GBS subsequent to mycoplasma infection had antigalactocerebroside antibody. Further study on antiglycolipid antibody is needed for understanding the pathogenetic mechanism of GBS.

  11. Small fiber neuropathy: Getting bigger!

    PubMed

    Chan, Amanda C Y; Wilder-Smith, Einar P

    2016-05-01

    Etiological and clinical heterogeneity of small fiber neuropathy (SFN) precludes a unifying approach and necessitates reliance on recognizable clinical syndromes. Symptoms of SFN arise from dysfunction in nociception, temperature, and autonomic modalities. This review focuses on SFN involving nociception and temperature, examining epidemiology, etiology, clinical presentation, diagnosis, pathophysiology, and management. Prevalence of SFN is 52.95 per 100,000 population, and diabetes and idiopathic are the most common etiologies. Dysesthesia, allodynia, pain, burning, and coldness sensations frequently present in a length-dependent pattern. Additional autonomic features in gastrointestinal, urinary, or cardiovascular systems are frequent but poorly objectified. SFN is diagnosed by intraepidermal nerve fiber density and quantitative sensory and autonomic tests in combination with normal nerve conduction. Pathophysiological understanding centers on sodium channel dysfunction, and genetic forms are beginning to be understood. Treatment is directed at the underlying etiology supported by symptomatic treatment using antidepressants and anticonvulsants. Little is known about long-term outcomes, and systematic cohort studies are needed.

  12. Molecular study of patients with auditory neuropathy.

    PubMed

    Carvalho, Guilherme Machado De; Ramos, Priscila Zonzini; Castilho, Arthur Menino; Guimarães, Alexandre Caixeta; Sartorato, Edi Lúcia

    2016-07-01

    Auditory neuropathy is a type of hearing loss that constitutes a change in the conduct of the auditory stimulus by the involvement of inner hair cells or auditory nerve synapses. It is characterized by the absence or alteration of waves in the examination of brainstem auditory evoked potentials, with otoacoustic and/or cochlear microphonic issues. At present, four loci associated with non‑syndromic auditory neuropathy have been mapped: Autosomal recessive deafness‑9 [DFNB9; the otoferlin (OTOF) gene] and autosomal recessive deafness‑59 [DFNB59; the pejvakin (PJVK) gene], associated with autosomal recessive inheritance; the autosomal dominant auditory neuropathy gene [AUNA1; the diaphanous‑3 (DIAPH3) gene]; and AUNX1, linked to chromosome X. Furthermore, mutations of connexin 26 [the gap junction β2 (GJB2) gene] have also been associated with the disease. OTOF gene mutations exert a significant role in auditory neuropathy. In excess of 80 pathogenic mutations have been identified in individuals with non‑syndromic deafness in populations of different origins, with an emphasis on the p.Q829X mutation, which was found in ~3% of cases of deafness in the Spanish population. The identification of genetic alterations responsible for auditory neuropathy is one of the challenges contributing to understand the molecular bases of the different phenotypes of hearing loss. Thus, the present study aimed to investigate molecular changes in the OTOF gene in patients with auditory neuropathy, and to develop a DNA chip for the molecular diagnosis of auditory neuropathy using mass spectrometry for genotyping. Genetic alterations were investigated in 47 patients with hearing loss and clinical diagnosis of auditory neuropathy, and the c.35delG mutation in the GJB2 gene was identified in three homozygous patients, and the heterozygous parents of one of these cases. Additionally, OTOF gene mutations were tracked by complete sequencing of 48 exons, although these results

  13. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury.

    PubMed

    Kızılay, Zahir; Erken, Haydar Ali; Çetin, Nesibe Kahraman; Aktaş, Serdar; Abas, Burçin İrem; Yılmaz, Ali

    2016-10-01

    The aim of this study was to investigate the effects of boric acid in experimental acute sciatic nerve injury. Twenty-eight adult male rats were randomly divided into four equal groups (n = 7): control (C), boric acid (BA), sciatic nerve injury (I), and sciatic nerve injury + boric acid treatment (BAI). Sciatic nerve injury was generated using a Yasargil aneurysm clip in the groups I and BAI. Boric acid was given four times at 100 mg/kg to rats in the groups BA and BAI after injury (by gavage at 0, 24, 48 and 72 hours) but no injury was made in the group BA. In vivo electrophysiological tests were performed at the end of the day 4 and sciatic nerve tissue samples were taken for histopathological examination. The amplitude of compound action potential, the nerve conduction velocity and the number of axons were significantly lower and the myelin structure was found to be broken in group I compared with those in groups C and BA. However, the amplitude of the compound action potential, the nerve conduction velocity and the number of axons were significantly greater in group BAI than in group I. Moreover, myelin injury was significantly milder and the intensity of nuclear factor kappa B immunostaining was significantly weaker in group BAI than in group I. The results of this study show that administration of boric acid at 100 mg/kg after sciatic nerve injury in rats markedly reduces myelin and axonal injury and improves the electrophysiological function of injured sciatic nerve possibly through alleviating oxidative stress reactions.

  14. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury

    PubMed Central

    Kızılay, Zahir; Erken, Haydar Ali; Çetin, Nesibe Kahraman; Aktaş, Serdar; Abas, Burçin İrem; Yılmaz, Ali

    2016-01-01

    The aim of this study was to investigate the effects of boric acid in experimental acute sciatic nerve injury. Twenty-eight adult male rats were randomly divided into four equal groups (n = 7): control (C), boric acid (BA), sciatic nerve injury (I), and sciatic nerve injury + boric acid treatment (BAI). Sciatic nerve injury was generated using a Yasargil aneurysm clip in the groups I and BAI. Boric acid was given four times at 100 mg/kg to rats in the groups BA and BAI after injury (by gavage at 0, 24, 48 and 72 hours) but no injury was made in the group BA. In vivo electrophysiological tests were performed at the end of the day 4 and sciatic nerve tissue samples were taken for histopathological examination. The amplitude of compound action potential, the nerve conduction velocity and the number of axons were significantly lower and the myelin structure was found to be broken in group I compared with those in groups C and BA. However, the amplitude of the compound action potential, the nerve conduction velocity and the number of axons were significantly greater in group BAI than in group I. Moreover, myelin injury was significantly milder and the intensity of nuclear factor kappa B immunostaining was significantly weaker in group BAI than in group I. The results of this study show that administration of boric acid at 100 mg/kg after sciatic nerve injury in rats markedly reduces myelin and axonal injury and improves the electrophysiological function of injured sciatic nerve possibly through alleviating oxidative stress reactions. PMID:27904499

  15. Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice

    PubMed Central

    2011-01-01

    Background A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV) followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG) and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH) wide dynamic range neurons in oxaliplatin-treated mice Results We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH. Conclusions Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds. PMID:21521528

  16. New Treatments for Nonarteritic Anterior Ischemic Optic Neuropathy.

    PubMed

    Foroozan, Rod

    2017-02-01

    Despite increasing knowledge about the risk factors and clinical findings of nonarteritic anterior ischemic optic neuropathy (NAION), the treatment of this optic neuropathy has remained limited and without clear evidence-based benefit. Historical treatments of NAION are reviewed, beginning with the Ischemic Optic Neuropathy Decompression Trial. More recent treatments are placed within the historical context and illustrate the need for evidence-based therapy for ischemic optic neuropathy.

  17. Auditory Neuropathy Spectrum Disorder Masquerading as Social Anxiety

    PubMed Central

    Rao, Mukund G.; Mishra, Shree; Varambally, Shivarama; Nagarajarao, Shivashankar; Gangadhar, Bangalore N.

    2015-01-01

    The authors report a case of a 47-year-old man who presented with treatment-resistant anxiety disorder. Behavioral observation raised clinical suspicion of auditory neuropathy spectrum disorder. The presence of auditory neuropathy spectrum disorder was confirmed on audiological investigations. The patient was experiencing extreme symptoms of anxiety, which initially masked the underlying diagnosis of auditory neuropathy spectrum disorder. Challenges in diagnosis and treatment of auditory neuropathy spectrum disorder are discussed. PMID:26351622

  18. Clinical Profile of Peripheral Neuropathy in Leprosy.

    PubMed

    Sarker, U K; Uddin, M J; Chowdhury, R; Roy, N; Bhattacharjee, M; Roy, J

    2015-10-01

    The objectives of the study were to see the association of peripheral neuropathy in leprosy and to find out the clinical profile of peripheral neuropathy and disability status in leprosy. It was descriptive type of cross sectional study was conducted among the cases of leprosy attended in the out-patient departments of neurology, Mymensingh Medical College Hospital (MMCH) and Mymensingh tuberculosis and leprosy hospital that fulfilled the inclusion criteria were included in this study, during the study period of January 2010 to December 2011.In this study of 62 cases revealed that leprosy is more common in male (71%) people and 21% leprosy patient had contact with known case of leprosy. Leprosy causes peripheral neuropathy (61.3%). Duration of occurrence of peripheral neuropathy was prolonged (>6 month) in most of the patients (47.4%) and the disease progression was also slow (63.2%). Numbness was complained by 89.4% patients and 65.8% subjects complained of weakness of limbs. Deformities and ulcers were present in 26.3% and 50% of patients respectively. Ulnar nerve (43.6%), Lateral popliteal nerve (41.9%), Posterior tibial nerve (41.9%) and Great auricular nerve (17.7%) were the most commonly involved thickened peripheral nerves. The rate of visible physical impairment (WHO Grade 2 disability) among people affected by leprosy in feet was 27.4% and in hands was 16.1%. The position and vibration sense was found to normal all patients of peripheral neuropathy.

  19. [Vasculitic neuropathy: novel classification, diagnosis and treatment].

    PubMed

    Kanda, Takashi

    2014-01-01

    The international standard of nomenclature and classification in vasculitis, CHCC 1994,was revised as CHCC 2012. In the first part of this review article I briefly summarized the CHCC 2012 and pointed out the changes in this revision, especially on the disorders related to vasculitic neuropathy. Notable changes include the introduction of new terms such as granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis. In the second part, I mentioned the tips for the diagnosis and treatment of vasculitic neuropathy. Because most of the vasculitic neuropathy patients require rigorous, long-standing immunosuppressive therapy, the accurate diagnosis based on the pathological detection of vasculitic changes is mandatory. In this regard, the value of sural nerve biopsy is still not ignorable. In the treatment of vascultic neuropathy, there are no controlled treatment trials and clinical practice is guided by experience from case series and indirectly by analogy with systemic vasculitis. Although combined therapy using prednisolone and cyclophosphamide is usually recommended by experts, tailor-made treatment regimen based on the conditions of each patient would produce the best outcome in vasculitic neuropathy.

  20. Re-Treatment With Ethambutol After Toxic Optic Neuropathy.

    PubMed

    Bouffard, Marc A; Nathavitharana, Ruvandhi R; Yassa, David S; Torun, Nurhan

    2017-03-01

    There are no data in the literature regarding the safety of re-treatment with ethambutol for recurrent mycobacterial infection after prior ethambutol-induced optic neuropathy. We describe a patient who developed optic neuropathy attributed to ethambutol, recovered fully after drug withdrawal, and tolerated a 14-month long re-treatment 10 years later without developing recurrent optic neuropathy.

  1. Rheumatoid neuropathy: a histological and electrophysiological study

    PubMed Central

    Weller, R. O.; Bruckner, F. E.; Chamberlain, M. Anne

    1970-01-01

    Peripheral nerves in five patients with rheumatoid neuropathy were examined electrophysiologically and by sural nerve biopsy. There was close correlation between the clinical severity of the disease and the degree of nerve damage found histologically and by EMG. Group 1 patients with a mild distal sensory neuropathy showed varying degrees of axonal degeneration in the large myelinated fibres and some segmental demyelination. Group 2 patients with a severe, rapidly progressive sensori-motor neuropathy had extensive loss of myelinated fibres. In one case all the large fibres had degenerated. The second case had lost both large and small myelinated fibres together with many of the non-myelinated axons. The major nerve damage in both groups appeared to be axonal degeneration but some segmental demyelination was detected. Occlusive vascular disease in the vasa nervorum was considered to be the major cause of the nerve damage. Images PMID:4320255

  2. [A new physiopathological classification of diabetic neuropathy].

    PubMed

    Olmos, Pablo R; Niklitschek, Sergio; Olmos, Roberto I; Faúndez, Jorge I; Quezada, Thomas A; Bozinovic, Milan A; Niklitschek, Ian A; Acosta, Jorge; Valencia, Claudio N; Bravo, Felipe A

    2012-12-01

    Nowadays, Diabetic Neuropathy (DN) is considered the most common cause of peripheral neuropathy in clinical practice. It can affect sensitive, motor or autonomic nerve fibers, with symmetric, asymmetric, acute or chronic presentations. Due to this variability, with multiple physiopathologic mechanisms involved, a complex clinical classification has been used until recently. The aim of this review is to present a new classification of diabetic neuropathy, based on its physiopathology. It is divided in metabolic microvascular and hypoxic, autoimmune and inflammatory, compressive, secondary to complications of diabetes and related to treatment. It must be understood that DN is not just a functional disease, but a complication of diabetes with molecular and pathological substrates caused by hyperglycemia. Therefore, normalization of blood glucose is a fundamental step towards the successful prevention and treatment of DN.

  3. Towards a functional pathology of hereditary neuropathies.

    PubMed

    Weis, Joachim; Claeys, Kristl G; Roos, Andreas; Azzedine, Hamid; Katona, Istvan; Schröder, J Michael; Senderek, Jan

    2017-04-01

    A growing number of hereditary neuropathies have been assigned to causative gene defects in recent years. The study of human nerve biopsy samples has contributed substantially to the discovery of many of these neuropathy genes. Genotype-phenotype correlations based on peripheral nerve pathology have provided a comprehensive picture of the consequences of these mutations. Intriguingly, several gene defects lead to distinguishable lesion patterns that can be studied in nerve biopsies. These characteristic features include the loss of certain nerve fiber populations and a large spectrum of distinct structural changes of axons, Schwann cells and other components of peripheral nerves. In several instances the lesion patterns are directly or indirectly linked to the known functions of the mutated gene. The present review is designed to provide an overview on these characteristic patterns. It also considers other aspects important for the manifestation and pathology of hereditary neuropathies including the role of inflammation, effects of chemotherapeutic agents and alterations detectable in skin biopsies.

  4. [Diabetic neuropathies. IV. Autonomous neuropathy. Peripheral sympathetic innervation and the cardiovascular system].

    PubMed

    Gentile, S; Marmo, R; Costume, A; Persico, M; Bronzino, P; Contaldi, P; Stroffolini, T

    1984-04-28

    The clinical conditions due to damage to the peripheral sympathetic nervous system during diabetic neuropathy mainly involve alterations to subcutaneous vasomotility , temperature body regulation and exudation, which may take form of hyper or hypoactivity. Gustatory exudation and local anhydrosis are described in detail as well as the connection with aggravating factors like long duration, poor balance and early onset of diabetes mellitus . Change in the relevant cardiovascular reflexes, commonly used in diagnosing diabetic neuropathy, are also analysed with a discussion of their physiopathological background and clinical significance. Finally the painless infarct, sudden death and abnormal response to hypoglycaemia, that are the common features of diabetic neuropathy, are also described.

  5. Early Electrophysiological Abnormalities and Clinical Neuropathy

    PubMed Central

    Hyllienmark, Lars; Alstrand, Nils; Jonsson, Björn; Ludvigsson, Johnny; Cooray, Gerald; Wahlberg-Topp, Jeanette

    2013-01-01

    OBJECTIVE The aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Fifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 ± 3.22 years (range 7–22 years) of age, and duration of diabetes was 6.8 ± 3.3 years. At follow-up, patients were 20–35 years of age, and disease duration was 20 ± 5.3 years (range 10–31 years). RESULTS At baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P < 0.010–0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA1c (R2 = 48%, odds ratio 7.9, P < 0.002) followed by peroneal MCV at baseline (R2 = 38%, odds ratio 0.6, P < 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA1c and then only peroneal MCV at baseline entered significantly (R2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA1c (ρ = 0.40, P < 0.002) than with follow-up HbA1c (ρ = 0.034, P < 0.007). CONCLUSIONS Early defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA1c during the first years of the disease. PMID:23723354

  6. Polyethylene Glycol-Fused Allografts Produce Rapid Behavioral Recovery After Ablation of Sciatic Nerve Segments

    PubMed Central

    Riley, D.C.; Bittner, G.D.; Mikesh, M.A.; Cardwell, N.L.; Pollins, A.C.; Ghergherehchi, C.L.; Sunkesula, S.R. Bhupanapadu; Ha, T.N.; Hall, B.T.D.; Poon, A.D.; Pyarali, M.; Boyer, R.B.; Mazal, A.T.; Munoz, N.; Trevino, R.C.; Schallert, T.; Thayer, W.P.

    2014-01-01

    Restoration of neuronal functions by outgrowths regenerating at ~1mm/d from the proximal stumps of severed peripheral nerves takes many weeks or months, if it occurs at all, especially after ablation of nerve segments. Distal segments of severed axons typically degenerate in 1–3 days. The purpose of this study was to show that Wallerian degeneration could be prevented or retarded and lost behavioral function restored following ablation of 0.5 – 1 cm segments of rat sciatic nerves in host animals. This is achieved using 0.8 – 1.1cm microsutured donor allografts treated with bioengineered solutions varying in ionic and polyethylene glycol (PEG) concentrations (modified PEG-fusion procedure), being careful not to stretch any portion of donor or host sciatic nerves. Our data show that PEG-fusion permanently restores axonal continuity within minutes as initially assessed by action potential conduction and intracellular diffusion of dye. Behavioral functions mediated by the sciatic nerve are largely restored within 2 – 4 wk as measured by the Sciatic Functional Index (SFI). Increased restoration of sciatic behavioral functions after ablating 0.5 – 1 cm segments is associated with greater numbers of viable myelinated axons within, and distal to, PEG-fused allografts. Many such viable myelinated axons are almost-certainly spared from Wallerian degeneration by PEG-fusion. PEG-fusion of donor allografts may produce a paradigm-shift in the treatment of peripheral nerve injuries. PMID:25425242

  7. Deep gluteal space problems: piriformis syndrome, ischiofemoral impingement and sciatic nerve release

    PubMed Central

    Carro, Luis Perez; Hernando, Moises Fernandez; Cerezal, Luis; Navarro, Ivan Saenz; Fernandez, Ana Alfonso; Castillo, Alexander Ortiz

    2016-01-01

    Summary Background Deep gluteal syndrome (DGS) is an underdiagnosed entity characterized by pain and/or dysesthesias in the buttock area, hip or posterior thigh and/or radicular pain due to a non-discogenic sciatic nerve entrapment in the subgluteal space. Multiple pathologies have been incorporated in this all-included “piriformis syndrome”, a term that has nothing to do with the presence of fibrous bands, obturator internus/gemellus syndrome, quadratus femoris/ischiofemoral pathology, hamstring conditions, gluteal disorders and orthopedic causes. Methods This article describes the subgluteal space anatomy, reviews known and new etiologies of DGS, and assesses the role of the radiologist and orthopaedic surgeons in the diagnosis, treatment and postoperative evaluation of sciatic nerve entrapments. Conclusion DGS is an under-recognized and multifactorial pathology. The development of periarticular hip endoscopy has led to an understanding of the pathophysiological mechanisms underlying piriformis syndrome, which has supported its further classification. The whole sciatic nerve trajectory in the deep gluteal space can be addressed by an endoscopic surgical technique. Endoscopic decompression of the sciatic nerve appears useful in improving function and diminishing hip pain in sciatic nerve entrapments, but requires significant experience and familiarity with the gross and endoscopic anatomy. Level of evidence IV. PMID:28066745

  8. Oxidative damage is ameliorated by curcumin treatment in brain and sciatic nerve of diabetic rats.

    PubMed

    Acar, Abdullah; Akil, Esref; Alp, Harun; Evliyaoglu, Osman; Kibrisli, Erkan; Inal, Ali; Unan, Fatma; Tasdemir, Nebahat

    2012-07-01

    To date, there have not been enough studies about the effects of curcumin against oxidative stress on sciatic nerves caused by streptozotocin (STZ) in diabetic rats. Therefore, this study was undertaken to determine whether curcumin, by virtue of its antioxidant properties, could affect the oxidant/antioxidant balance in the sciatic nerve and brain tissues of streptozotocin (STZ)-induced diabetic rats. A total of 28 rats were randomly divided into four groups of seven rats each: normal controls, only curcumin treated, diabetic controls, and diabetics treated with curcumin. Biomarkers-malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and NO levels-for oxidative stress in the brain and sciatic nerve tissues of the rats were measured. We found a significant increase in MDA, NO, TOS, and OSI, along with a reduction in TAS levels in the brains and sciatic nerves of the STZ-induced diabetic rats (for both parameters p < 0.05). The MDA, TOS, OSI, and NO levels in these tissues were significantly reduced in the curcumin-treated diabetic group compared to the untreated diabetic group. In conclusion, the results of this study suggested that curcumin exhibits neuroprotective effects against oxidative damage in the brain and sciatic tissues of diabetic rats.

  9. Solitary ischial osteochondroma: an unusual cause of sciatic pain: case report.

    PubMed

    de Moraes, Frederico Barra; Silva, Paulo; do Amaral, Rogério Andrade; Ramos, Frederico Faleiro; Silva, Rômulo Orlando; de Freitas, Diogo Azevedo

    2014-01-01

    The aim was to report on a rare case of osteochondroma of the left ischium, which evolved with compression of the sciatic nerve, thus causing sciatic pain in the homolateral lower limb. The patient was female and presented sciatic pain that was treated clinically for one year. However, the pain evolved with increasing intensity and worsened with hip movement. This was associated with diminished motor force and paresthesia of the homolateral lower limb. Radiological investigation of the region showed a bone lesion in the external portion of the left ischium, in the path of the sciatic nerve. Tomographic reconstruction showed cortical continuity with the bone of origin, i.e., a pattern characteristic of osteochondroma. En-bloc resection of the lesion was performed using the Kocher-Langerbeck route, and the anatomopathological analysis proved that it was an osteochondroma. The patient's neurological symptoms improved and, after two months of follow-up, she remained asymptomatic and without any signs of recurrence. Since osteochondroma is the commonest benign bone tumor, it should be taken into consideration in the diagnostic investigation of compressive tumor lesions that could affect the sciatic nerve.

  10. Solitary ischial osteochondroma: an unusual cause of sciatic pain: case report☆☆☆

    PubMed Central

    de Moraes, Frederico Barra; Silva, Paulo; do Amaral, Rogério Andrade; Ramos, Frederico Faleiro; Silva, Rômulo Orlando; de Freitas, Diogo Azevedo

    2014-01-01

    The aim was to report on a rare case of osteochondroma of the left ischium, which evolved with compression of the sciatic nerve, thus causing sciatic pain in the homolateral lower limb. The patient was female and presented sciatic pain that was treated clinically for one year. However, the pain evolved with increasing intensity and worsened with hip movement. This was associated with diminished motor force and paresthesia of the homolateral lower limb. Radiological investigation of the region showed a bone lesion in the external portion of the left ischium, in the path of the sciatic nerve. Tomographic reconstruction showed cortical continuity with the bone of origin, i.e., a pattern characteristic of osteochondroma. En-bloc resection of the lesion was performed using the Kocher-Langerbeck route, and the anatomopathological analysis proved that it was an osteochondroma. The patient's neurological symptoms improved and, after two months of follow-up, she remained asymptomatic and without any signs of recurrence. Since osteochondroma is the commonest benign bone tumor, it should be taken into consideration in the diagnostic investigation of compressive tumor lesions that could affect the sciatic nerve. PMID:26229819

  11. Predicting Acute and Persistent Neuropathy Associated with Oxaliplatin

    PubMed Central

    Alejandro, Linh; Behrendt, Carolyn E.; Chen, Kim; Openshaw, Harry; Shibata, Stephen

    2014-01-01

    Objectives We sought to predict oxaliplatin-associated peripheral neuropathy during modified FOLFOX6 (mFOLFOX6) therapy. Methods In a 50% female sample, patients with previously untreated, primary or recurrent colorectal cancer were followed through a first course of mFOLFOX6 with oxaliplatin 85 mg/m2 every 2 weeks. Accounting for correlation among a subject's cycles, logistic regression estimated per-cycle risk of acute (under 14 days) and persistent (14 days or more) neuropathy. Proportional hazards regression predicted time to persistent neuropathy. Results Among mFOLFOX6 recipients (n=50, age 58.9 +10.1 years), 36% received concomitant bevacizumab. Of total cycles, 94.2% (422/448) were evaluable. Most (84%) subjects reported neuropathy at least once: 74% reported acute and 48% reported persistent symptoms. On multivariate analysis, risk factors shared by acute and persistent neuropathy were body-surface area >2.0, acute neuropathy in a past cycle, and lower body weight. In addition, risk of acute neuropathy decreased with age (adjusted for renal function and winter season), while risk of persistent neuropathy increased with cumulative dose of oxaliplatin and persistent neuropathy in a past cycle. Concomitant bevacizumab was not a risk factor when administered in Stage IV disease but was associated with persistent neuropathy when administered experimentally in Stage III. Females had no increased risk of either form of neuropathy. After 3 cycles, weight, body-surface area, and prior acute neuropathy predicted time to persistent neuropathy. Conclusions Routinely available clinical factors predict acute and persistent neuropathy associated with oxaliplatin. When validated, the proposed prognostic score for persistent neuropathy can help clinicians counsel patients about chemotherapy. PMID:22547012

  12. Autoimmune neuropathies associated to rheumatic diseases.

    PubMed

    Martinez, Alberto R M; Faber, Ingrid; Nucci, Anamarli; Appenzeller, Simone; França, Marcondes C

    2017-04-01

    Systemic manifestations are frequent in autoimmune rheumatic diseases and include peripheral nervous system damage. Neuron cell body, axons and myelin sheath may all be affected in this context. This involvement results in severe and sometimes disabling symptoms. Sensory, motor and autonomic features may be present in different patterns that emerge as peculiar clinical pictures. Prompt recognition of these neuropathies is pivotal to guide treatment and reduce the risks of long term disability. In this review, we aim to describe the main immune-mediated neuropathies associated to rheumatic diseases: sensory neuronopathies, multiple mononeuropathies and chronic inflammatory demyelinating polyradiculoneuropathy, with an emphasis on clinical features and therapeutic options.

  13. [Optic neuropathy induced by thinner sniffing].

    PubMed

    Kohriyama, K; Hori, H; Murai, Y; Ninomiya, H; Tsukamoto, Y

    1989-12-01

    A case of optic neuropathy induced by thinner sniffing is reported. A 17-year-old girl, who had been sniffing a lacquer thinner for three months, suffered acute blindness followed by optic atrophy. Brain computed tomography revealed symmetrical low attenuation areas in the bilateral putamen. An analysis of the thinner by gas chromatography showed that its major components in a vaporized state were methyl alcohol and metyhl acetate. The optic neuropathy was induced by these solvents. In the diagnosis of the intoxication of mixed organic solvents, the measurement of each solvent in its vapor phase is considered to be quite important.

  14. Ischemic Neuropathy Associated with Livedoid Vasculitis

    PubMed Central

    Kim, Jee-Eun; Park, Su-Yeon; Sinn, Dong In; Kim, Sung-Min; Hong, Yoon-Ho; Park, Kyung Seok; Lee, Kwang-Woo

    2011-01-01

    Background Livedoid vasculitis is a chronic dermatological problem with an unclear etiology. Clinical findings are petechiae with painful ulcers in both lower extremities, which heal to become hyperpigmented and porcelain-white satellite lesions. There are only a few reported cases of livedoid vasculitis presenting in combination with peripheral neuropathy. Case Report We report the first case of a Korean patient presenting with mononeuritis multiplex combined with livedoid vasculitis, which was confirmed by electrophysiological and pathological studies. Conclusions Our report supports the possible vaso-occlusive etiology of livedoid vasculitis in multifocal ischemic neuropathy. PMID:22259622

  15. Minoxidil is a potential neuroprotective drug for paclitaxel-induced peripheral neuropathy.

    PubMed

    Chen, Yi-Fan; Chen, Li-Hsien; Yeh, Yu-Min; Wu, Pei-Ying; Chen, Yih-Fung; Chang, Lian-Yun; Chang, Jang-Yang; Shen, Meng-Ru

    2017-03-28

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. No medication has been shown to be effective in the treatment of CIPN. This study aims to integrate the image-based high-content screening, mouse behavior models and mechanistic cell-based assays to discover potential neuroprotective drugs. Among screened compounds, minoxidil showed the most potent neuroprotective effect against paclitaxel, with regard to neurite outgrowth of dorsal root ganglia (DRG). Minoxidil protected mice from thermal insensitivity and alleviated mechanical allodynia in paclitaxel-treated mice. The ultrastructure and quantified G-ratio of myelin integrity of sciatic nerve tissues supported the observations in mouse behavioral tests. The mechanistic study on DRG neurons suggested that minoxidil suppressed neuroinflammation and remodeled the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, minoxidil showed a synergistic anti-tumor effect with paclitaxel both in tumor xenograft models of cervical and breast cancer. Interestingly, the quantitative assays on hair length and hair growth both exhibited that minoxidil significantly improved the hair quality after chemotherapy. Since minoxidil is a drug approved by the Food and Drug Administration (FDA), the safety and biocompatibility are well documented. The immediate next step is to launch an early-stage clinical trial intending to prevent CIPN by minoxidil.

  16. Minoxidil is a potential neuroprotective drug for paclitaxel-induced peripheral neuropathy

    PubMed Central

    Chen, Yi-Fan; Chen, Li-Hsien; Yeh, Yu-Min; Wu, Pei-Ying; Chen, Yih-Fung; Chang, Lian-Yun; Chang, Jang-Yang; Shen, Meng-Ru

    2017-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. No medication has been shown to be effective in the treatment of CIPN. This study aims to integrate the image-based high-content screening, mouse behavior models and mechanistic cell-based assays to discover potential neuroprotective drugs. Among screened compounds, minoxidil showed the most potent neuroprotective effect against paclitaxel, with regard to neurite outgrowth of dorsal root ganglia (DRG). Minoxidil protected mice from thermal insensitivity and alleviated mechanical allodynia in paclitaxel-treated mice. The ultrastructure and quantified G-ratio of myelin integrity of sciatic nerve tissues supported the observations in mouse behavioral tests. The mechanistic study on DRG neurons suggested that minoxidil suppressed neuroinflammation and remodeled the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, minoxidil showed a synergistic anti-tumor effect with paclitaxel both in tumor xenograft models of cervical and breast cancer. Interestingly, the quantitative assays on hair length and hair growth both exhibited that minoxidil significantly improved the hair quality after chemotherapy. Since minoxidil is a drug approved by the Food and Drug Administration (FDA), the safety and biocompatibility are well documented. The immediate next step is to launch an early-stage clinical trial intending to prevent CIPN by minoxidil. PMID:28349969

  17. 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

  18. 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.

  19. [Diabetic peripheral neuropathy: reflections and drug-rehabilitative treatment].

    PubMed

    Pagano, Lucia; Proietto, Maria; Biondi, Roberto

    2009-01-01

    About 60 to 70 percent of people with diabetes have some neuropathy. Diabetic neuropathy can be classified as peripheral, autonomic, proximal, focal and multifocal or mixed. Peripheral neuropathy, the most common type of diabetic neuropathy, causes pain and/or loss of feeling in the toes, feet, legs, hands, and arms; extreme sensitivity to touch, loss of balance and coordination; muscle weakness and loss of reflexes, especially at the ankle, leading to changes in the way a person walks. The aim of this study is to underline the importance of drug and rehabilitative approach in the therapy of peripheral neuropathy, that frequently influences both diabetes mellitus type 1 and diabetes mellitus type 2.

  20. The electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies.

    PubMed

    Lewis, R A; Sumner, A J

    1982-06-01

    We compared the electrodiagnostic studies of 40 patients with chronic acquired demyelinative neuropathy and 18 patients with familial demyelinative neuropathy. Patients with acquired neuropathy had differential slowing of conduction velocity when distal latencies were compared with more proximal conduction velocities in the same nerve, when equivalent segments of different nerves were compared, and when dispersion of compound motor action potentials was examined. Conduction block was noted in some patients. Patients with familial disease had uniform conduction slowly of all nerve segments, and conduction block was not seen. Chronic acquired demyelinative neuropathy is characterized by multifocal slowing of nerve conduction, whereas familial demyelinative neuropathy is characterized by uniform conduction slowing.

  1. Diagnosis and therapeutic options for peripheral vasculitic neuropathy

    PubMed Central

    2015-01-01

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

  2. Redoxins in peripheral neurons after sciatic nerve injury.

    PubMed

    Valek, Lucie; Kanngießer, Maike; Häussler, Annett; Agarwal, Nitin; Lillig, Christopher Horst; Tegeder, Irmgard

    2015-12-01

    Peripheral nerve injury causes redox stress in injured neurons by upregulations of pro-oxidative enzymes, but most neurons survive suggesting an activation of endogenous defense against the imbalance. As potential candidates we assessed thioredoxin-fold proteins, called redoxins, which maintain redox homeostasis by reduction of hydrogen peroxide or protein dithiol-disulfide exchange. Using a histologic approach, we show that the peroxiredoxins (Prdx1-6), the glutaredoxins (Glrx1, 2, 3 and 5), thioredoxin (Txn1 and 2) and their reductases (Txnrd1 and 2) are expressed in neurons, glial and/or vascular cells of the dorsal root ganglia (DRGs) and in the spinal cord. They show distinct cellular and subcellular locations in agreement with the GO terms for "cellular component". The expression and localization of Glrx, Txn and Txnrd proteins was not affected by sciatic nerve injury but peroxiredoxins were upregulated in the DRGs, Prdx1 and Prdx6 mainly in non-neuronal cells and Prdx4 and Prdx5 in DRG neurons, the latter associated with an increase of respective mRNAs and protein accumulation in peripheral and/or central fibers. The upregulation of Prdx4 and Prdx5 in DRG neurons was reduced in mice with a cre-loxP mediated deficiency of hypoxia inducible factor 1 alpha (HIF1α) in these neurons. The results identify Prdx4 and Prdx5 as endogenous HIF1α-dependent, transcriptionally regulated defenders of nerve injury evoked redox stress that may be important for neuronal survival and regeneration.

  3. Entrapment of the sciatic nerve at the linea aspera: A case report and literature review

    PubMed Central

    Monteleone, Giovanni; Stevanato, Giorgio

    2016-01-01

    Background: Nontraumatic, non-neoplastic sciatic nerve entrapment at the level of the thigh is extremely rare. In its course, in proximity of the linea aspera, the nerve is exposed to unexpected neuropathic syndromes associated with bone disorders. Case Description: A 67-year-old woman presented with a painful, neuropathic syndrome of the sciatic nerve, not resulting from any trauma and persisting for approximately 2 years. Imaging studies of the thigh showed a delimited zone of hyperostosis in the proximal third of the femoral diaphysis. The symptoms dramatically resolved after the patient underwent neurolysis of the tract of the nerve adjoining to the linea aspera. At the clinical checkup 2 years later, the patient remained free of pain. Conclusion: The diagnosis of sciatic nerve entrapment at the linea aspera may present considerable difficulties. The clinical history and physical examination sometimes motivate the exploration and neurolysis of the nerve at this site. PMID:27857853

  4. Sciatic nerve injury repair: a visualized analysis of research fronts and development trends.

    PubMed

    Liu, Guangyao; Jiang, Rui; Jin, Yan

    2014-09-15

    A total of 3,446 publications regarding sciatic nerve injury repair and protection indexed by Web of Science during 2000-2004 were used for a detailed analysis of temporal-spatial distribution characteristics. Reference co-citation networks of the 100 top-cited publications as per the number of total citations were created using the Web of Science database and the information visualization tool, CiteSpaceIII. The key words that showed high frequency in these publications were included for analyzing the research fronts and development trends for sciatic nerve injury repair and protection. Through word frequency trend analysis, studies on bone marrow mesenchymal stem cells, adipose-derived stem cells, and skeletal muscle-derived multipotent stem cells combined with tissue-engineered scaffold material will become the forefronts in the field of sciatic nerve injury repair and protection in the near future.

  5. Symptomatic Growth of a Thrombosed Persistent Sciatic Artery Aneurysm after Bypass and Distal Exclusion

    PubMed Central

    Kim, Song-Yi; Cho, Sungsin; Cho, Min-Ji; Min, Sang-il; Ahn, Sanghyun; Ha, Jongwon; Min, Seung-Kee

    2017-01-01

    A 71-year-old woman presented with an enlarging mass in the right buttock, with pain and tingling sensation in sitting position. Five years ago, she was diagnosed with acute limb ischemia due to acute thrombosis of right persistent sciatic artery (PSA), and she underwent successful thromboembolectomy and femoro-tibioperoneal trunk bypass. Computed tomography angiography revealed a huge PSA aneurysm (PSAA). During the previous bypass, the distal popliteal artery was ligated just above the distal anastomosis to exclude the PSAA, whose proximal end was already thrombosed. However, PSAA has grown to cause compression symptoms, and the mechanism of aneurysm growth can be ascribed to type 1a or type 2 endoleak. In order to relieve the compression symptoms, aneurysm excision was performed without any injury to the sciatic nerve. A postoperative tingling sensation due to sciatic-nerve stimulation in the supine position resolved spontaneously one month after surgery. PMID:28377910

  6. Recombinant hNeuritin Promotes Structural and Functional Recovery of Sciatic Nerve Injury in Rats

    PubMed Central

    Wang, Haiyan; Li, Xinli; Shan, Liya; Zhu, Jingling; Chen, Rong; Li, Yuan; Yuan, Wumei; Yang, Lei; Huang, Jin

    2016-01-01

    Neuritin is a new neurotropic factor implicated in nervous system development and plasticity. Studies have shown that Neuritin is upregulated in injured nerves, suggesting that it is involved in nerve repair. To test this hypothesis, we investigated whether recombinant human Neuritin could restore nerve structure and function in a rat model of sciatic nerve injury. Neuritin treatment had a dose-dependent effect on functional recovery 4 weeks after injury, as determined by the walking-track test. Similar trends were observed for gastrocnemius muscular strength and nerve conduction velocity. Additionally, sciatic nerve fiber density and organization as well as degree of remyelination were increased, while growth-associated protein 43 and neurofilament 200 expression was upregulated upon treatment with Neuritin. These findings demonstrate that Neuritin stimulates nerve regeneration and functional recovery and thus promotes the repair of injured sciatic nerves. PMID:28066172

  7. Maternal Bilateral Radial Neuropathy During Childbirth in Hereditary Neuropathy With a Predisposition to Pressure Palsies (HNPP).

    PubMed

    Molloy, F M; Raynor, E M; Rutkove, S B

    2000-03-01

    A 30-year-old woman developed severe bilateral radial neuropathies during vaginal delivery of twins, likely secondary to positioning and muscular effort. Subsequent evaluation led to the diagnosis of hereditary neuropathy with predisposition to pressure palsies. Avoidance of prolonged muscular effort in the arms in conjunction with medial intervention to shorten the second stage of labor may help prevent debilitating radial nerve injury in women with this disorder.

  8. Anthropometric Study of the Piriformis Muscle and Sciatic Nerve: A Morphological Analysis in a Polish Population.

    PubMed

    Haładaj, Robert; Pingot, Mariusz; Polguj, Michał; Wysiadecki, Grzegorz; Topol, Mirosław

    2015-12-02

    BACKGROUND The aim of this study was to determine relationships between piriformis muscle (PM) and sciatic nerve (SN) with reference to sex and anatomical variations. MATERIAL AND METHODS Deep dissection of the gluteal region was performed on 30 randomized, formalin-fixed human lower limbs of adults of both sexes of the Polish population. Anthropometric measurements were taken and then statistically analyzed. RESULTS The conducted research revealed that, apart from the typical structure of the piriformis muscle, the most common variation was division of the piriformis muscle into two heads, with the common peroneal nerve running between them (20%). The group with anatomical variations of the sciatic nerve course displayed greater diversity of morphometric measurement results. There was a statistically significant correlation between the lower limb length and the distance from the sciatic nerve to the greater trochanter in the male specimens. On the other hand, in the female specimens, a statistically significant correlation was observed between the lower limb length and the distance from the sciatic nerve to the ischial tuberosity. The shortest distance from the sciatic nerve to the greater trochanter measured at the level of the inferior edge of the piriformis was 21 mm, while the shortest distance to the ischial tuberosity was 63 mm. Such correlations should be taken into account during invasive medical procedures performed in the gluteal region. CONCLUSIONS It is possible to distinguish several anatomical variations of the sciatic nerve course within the deep gluteal region. The statistically significant correlations between some anthropometric measurements were only present within particular groups of male and female limbs.

  9. Anthropometric Study of the Piriformis Muscle and Sciatic Nerve: A Morphological Analysis in a Polish Population

    PubMed Central

    Haładaj, Robert; Pingot, Mariusz; Polguj, Michał; Wysiadecki, Grzegorz; Topol, Mirosław

    2015-01-01

    Background The aim of this study was to determine relationships between piriformis muscle (PM) and sciatic nerve (SN) with reference to sex and anatomical variations. Material/Methods Deep dissection of the gluteal region was performed on 30 randomized, formalin-fixed human lower limbs of adults of both sexes of the Polish population. Anthropometric measurements were taken and then statistically analyzed. Results The conducted research revealed that, apart from the typical structure of the piriformis muscle, the most common variation was division of the piriformis muscle into two heads, with the common peroneal nerve running between them (20%). The group with anatomical variations of the sciatic nerve course displayed greater diversity of morphometric measurement results. There was a statistically significant correlation between the lower limb length and the distance from the sciatic nerve to the greater trochanter in the male specimens. On the other hand, in the female specimens, a statistically significant correlation was observed between the lower limb length and the distance from the sciatic nerve to the ischial tuberosity. The shortest distance from the sciatic nerve to the greater trochanter measured at the level of the inferior edge of the piriformis was 21 mm, while the shortest distance to the ischial tuberosity was 63 mm. Such correlations should be taken into account during invasive medical procedures performed in the gluteal region. Conclusions It is possible to distinguish several anatomical variations of the sciatic nerve course within the deep gluteal region. The statistically significant correlations between some anthropometric measurements were only present within particular groups of male and female limbs. PMID:26629744

  10. Magnetic resonance imaging of radiation optic neuropathy

    SciTech Connect

    Zimmerman, C.F.; Schatz, N.J.; Glaser, J.S. )

    1990-10-15

    Three patients with delayed radiation optic neuropathy after radiation therapy for parasellar neoplasms underwent magnetic resonance imaging. The affected optic nerves and chiasms showed enlargement and focal gadopentetate dimeglumine enhancement. The magnetic resonance imaging technique effectively detected and defined anterior visual pathway changes of radionecrosis and excluded the clinical possibility of visual loss because of tumor recurrence.

  11. Arteriovenous Access: Infection, Neuropathy, and Other Complications.

    PubMed

    MacRae, Jennifer M; Dipchand, Christine; Oliver, Matthew; Moist, Louise; Yilmaz, Serdar; Lok, Charmaine; Leung, Kelvin; Clark, Edward; Hiremath, Swapnil; Kappel, Joanne; Kiaii, Mercedeh; Luscombe, Rick; Miller, Lisa M

    2016-01-01

    Complications of vascular access lead to morbidity and may reduce quality of life. In this module, we review both infectious and noninfectious arteriovenous access complications including neuropathy, aneurysm, and high-output access. For the challenging patients who have developed many complications and are now nearing their last vascular access, we highlight some potentially novel approaches.

  12. Painful peripheral neuropathy and sodium channel mutations.

    PubMed

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

    2015-06-02

    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.

  13. Luxury perfusion following anterior ischemic optic neuropathy.

    PubMed

    Friedland, S; Winterkorn, J M; Burde, R M

    1996-09-01

    We present five patients who developed luxury perfusion following anterior ischemic optic neuropathy in whom fluorescein angiography was misinterpreted as "capillary hemangioma" or neovascularization of the disc. In each case, the segment of disc hyperemia corresponded to a spared region of visual field. Luxury perfusion represents a reparative autoregulatory reaction to ischemia.

  14. Auditory Neuropathy Spectrum Disorder: A Review

    ERIC Educational Resources Information Center

    Norrix, Linda W.; Velenovsky, David S.

    2014-01-01

    Purpose: Auditory neuropathy spectrum disorder, or ANSD, can be a confusing diagnosis to physicians, clinicians, those diagnosed, and parents of children diagnosed with the condition. The purpose of this review is to provide the reader with an understanding of the disorder, the limitations in current tools to determine site(s) of lesion, and…

  15. Speech Perception in Individuals with Auditory Neuropathy

    ERIC Educational Resources Information Center

    Zeng, Fan-Gang; Liu, Sheng

    2006-01-01

    Purpose: Speech perception in participants with auditory neuropathy (AN) was systematically studied to answer the following 2 questions: Does noise present a particular problem for people with AN: Can clear speech and cochlear implants alleviate this problem? Method: The researchers evaluated the advantage in intelligibility of clear speech over…

  16. Mechanisms of diabetic neuropathy: axon dysfunction.

    PubMed

    Sima, Anders A F; Zhang, Weixian

    2014-01-01

    Diabetic neuropathy is the most common complication of diabetes. It shows a progressive development with sensory loss, pain and autonomic dysfunction as common symptoms. Pathologically it is characterized by a series of interrelated metabolic abnormalities with insulin deficiency and hyperglycemia as the initiating culprits. The neuropathy accompanying type 2DM (insulin resistance) and type 1DM (insulin deficiency) appears to differ as to their structural changes; the former showing a milder axonal involvement and segmental myelin breakdown, whereas the latter shows a more severe axonal atrophy and axonal loss. Based mainly on animal data we will describe the sequential neuropathologic changes and differences in the two types of diabetes. These differences are related to differences in a myriad of underlying sequential metabolic abnormalities, which will be dealt with in detail. How metabolic defects affect nerve function will be elaborated upon. The disorder does not only involve somatic peripheral nerves but also autonomic and central nerve tracts. Today no successful therapy exists for diabetic neuropathy. During the last 30 years several experimental drugs targeting the polyol-pathway and oxidative stress have been tested, but with limited or no success. Instead therapies targeting the initiating and overriding pathogenetic abnormalities, such as insulin-deficiency and hyperglycemia need to be employed. One such agent is the insulinomimetic C-peptide which has demonstrated significant therapeutic and preventive effects in type 1 diabetic patients. Not surprisingly this has been particularly successful following early intervention. However diabetic neuropathy still remains a major medical problem affecting millions of patients.

  17. Autonomic neuropathy and diabetic foot ulceration.

    PubMed

    Edmonds, M E; Nicolaides, K H; Watkins, P J

    1986-01-01

    Autonomic function was studied in three groups of insulin-dependent diabetic patients. Heart rate changes during deep breathing and on standing were significantly less in 28 patients with a recent history of foot ulceration compared with 40 patients with peripheral neuropathy but without ulceration (p less than 0.001) and 54 patients without neuropathy (p less than 0.001). Sympathetic function was assessed in 36 of these patients from peripheral arterial diastolic flow patterns obtained by Doppler ultrasound measurements and expressed as the pulsatility index (PI). Patients with a history of ulceration (n = 10) showed considerably increased diastolic flow (PI = 4.28 +/- 0.53, mean +/- S.E.M.) compared with 12 neuropathic patients with no history of ulceration (PI = 7.80 +/- 0.68, p less than 0.002) and 14 patients without neuropathy (PI = 9.55 +/- 0.89, p less than 0.002). Severely abnormal autonomic function occurs in association with neuropathic foot ulceration, but patients without ulcers have lesser degrees of autonomic neuropathy, thus a causal relationship has not been established.

  18. 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

  19. Ozone partially prevents diabetic neuropathy in rats.

    PubMed

    Erken, H A; Genç, O; Erken, G; Ayada, C; Gündoğdu, G; Doğan, H

    2015-02-01

    Neuropathy is one of the most common complications of diabetes mellitus. Although the beneficial effects of good blood glucose control on diabetic neuropathy are known, this control cannot completely prevent the occurrence and progression of diabetic neuropathy. The aim of this study was to investigate whether ozone prevents diabetic neuropathy. 36 adult female Sprague-Dawley rats were randomly divided into 6 groups (n=6): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). Diabetes was induced by a single injection of streptozotocin (60 mg/kg, intraperitoneal [i.p.]), after which insulin was administered (3 IU, i.p.) to the DI and DOI groups for 28 days, and 1.1 mg/kg (50 µg/ml) ozone was given to the O, DO, and DOI groups for 15 days. 4 weeks after the induction of diabetes, the nerve conduction velocity (NCV), amplitude of the compound action potential (CAP), total oxidant status (TOS), and total antioxidant status (TAS) were measured, and the oxidative stress index (OSI) was calculated. The NCV, amplitude of CAP, and TAS of the DI and DOI groups were higher than those of the D group; the amplitudes of CAP and TAS of the DO group were higher than those of the D group; and the TOS and OSI of the DO, DI, and DOI groups were lower than those of the D group. These findings indicate that ozone partially prevents diabetic neuropathy in rats. It appears that the preventive effects of ozone are mediated through oxidant/antioxidant mechanisms.

  20. Peptide Mimetic of the S100A4 Protein Modulates Peripheral Nerve Regeneration and Attenuates the Progression of Neuropathy in Myelin Protein P0 Null Mice

    PubMed Central

    Moldovan, Mihai; Pinchenko, Volodymyr; Dmytriyeva, Oksana; Pankratova, Stanislava; Fugleholm, Kåre; Klingelhofer, Jorg; Bock, Elisabeth; Berezin, Vladimir; Krarup, Christian; Kiryushko, Darya

    2013-01-01

    We recently found that S100A4, a member of the multifunctional S100 protein family, protects neurons in the injured brain and identified two sequence motifs in S100A4 mediating its neurotrophic effect. Synthetic peptides encompassing these motifs stimulated neuritogenesis and survival in vitro and mimicked the S100A4-induced neuroprotection in brain trauma. Here, we investigated a possible function of S100A4 and its mimetics in the pathologies of the peripheral nervous system (PNS). We found that S100A4 was expressed in the injured PNS and that its peptide mimetic (H3) affected the regeneration and survival of myelinated axons. H3 accelerated electrophysiological, behavioral and morphological recovery after sciatic nerve crush while transiently delaying regeneration after sciatic nerve transection and repair. On the basis of the finding that both S100A4 and H3 increased neurite branching in vitro, these effects were attributed to the modulatory effect of H3 on initial axonal sprouting. In contrast to the modest effect of H3 on the time course of regeneration, H3 had a long-term neuroprotective effect in the myelin protein P0 null mice, a model of dysmyelinating neuropathy (Charcot-Marie-Tooth type 1 disease), where the peptide attenuated the deterioration of nerve conduction, demyelination and axonal loss. From these results, S100A4 mimetics emerge as a possible means to enhance axonal sprouting and survival, especially in the context of demyelinating neuropathies with secondary axonal loss, such as Charcot-Marie-Tooth type 1 disease. Moreover, our data suggest that S100A4 is a neuroprotectant in PNS and that other S100 proteins, sharing high homology in the H3 motif, may have important functions in PNS pathologies. PMID:23508572

  1. The prevalence of diabetic peripheral neuropathy in an outpatient setting.

    PubMed

    Mimi, O; Teng, C L; Chia, Y C

    2003-10-01

    This study was undertaken to clinically estimate the prevalence of diabetic peripheral neuropathy amongst patients attending an outpatient clinic and to evaluate their risk factors for developing peripheral neuropathy. It was a cross-sectional study of 134 diabetes mellitus patients who attended the Primary Care Clinic, University Hospital, Kuala Lumpur. The patients were interviewed for their demographic data, past and present medical/surgical history, social history, personal habits and symptoms of peripheral neuropathy. Foot examination and clinical neurological tests were conducted and the presence of peripheral neuropathy was assessed. The main outcome measures were the Neuropathy Symptom Score and the Neuropathy Disability Score. The prevalence of diabetic peripheral neuropathy was found to be 50.7%. Peripheral neuropathy was related to the age of the patient and the duration of diabetes but did not seem to be significantly related to diabetic control. To conclude, there was a high prevalence of peripheral neuropathy amongst the diabetics in this study. These patients developed peripheral neuropathy at a younger age and shorter duration of diabetes compared to a similar study that was done in the UK.

  2. Impaired glucose tolerance and metabolic syndrome in idiopathic neuropathy.

    PubMed

    Smith, A Gordon

    2012-05-01

    Idiopathic neuropathy is one of the most common clinical problems encountered in general medical and neurological practices, accounting for up to 40% of all neuropathies in referral series. Several groups have reported an elevated prevalence of impaired glucose tolerance (IGT) in idiopathic neuropathy subjects, although the only carefully conducted case-control study suggested hypertriglyceridemia was a more important risk factor. The nature of the relationship between IGT and neuropathy is a subject of active debate. An evolving literature suggests metabolic syndrome, particularly dyslipidemia and obesity, are potent neuropathy risk factors for both idiopathic and diabetic neuropathy patients. Once established, diabetic neuropathy is likely to be very difficult to reverse. IGT-associated neuropathy, however, may be more amenable to therapy and could represent an ideal population in which to examine potential therapies for diabetes and obesity related neuropathies. Further research is needed to better define the epidemiological relation between IGT, metabolic syndrome, and neuropathy, its underlying pathophysiology, and to develop appropriate surrogate measures and clinical trials strategies.

  3. In Vivo Photonic Stimulation of Sciatic Nerve with a 1470 nm Laser

    PubMed Central

    Dautrebande, Marie; Doguet, Pascal; Gorza, Simon-Pierre; Delbeke, Jean; Botquin, Yohan; Nonclercq, Antoine

    2016-01-01

    Photonic stimulation is a new modality of nerve stimulation, which could overcome some of the electrical stimulation limitations. In this paper, we present the results of photonic stimulation of rodent sciatic nerve with a 1470 nm laser. Muscle activation was observed with radiant exposure of 0.084 J/cm². PMID:27990230

  4. Expression and regulation of redoxins at nociceptive signaling sites after sciatic nerve injury in mice

    PubMed Central

    Valek, Lucie; Kanngießer, Maike; Tegeder, Irmgard

    2015-01-01

    Injury of the sciatic nerve results in regulations of pro- and anti-oxidative enzymes at sites of nociceptive signaling including the injured nerve, dorsal root ganglia (DRGs), dorsal horn of the spinal cord, thalamus and somatosensory cortex (Valek et al., 2015) [1]. The present DiB paper shows immunohistochemistry of redoxins including peroxiredoxins (Prdx1–6), glutaredoxins (Glrx1, 2, 3, 5), thioredoxins (Txn1, 2) and thioredoxin reductases (Txnrd1, 2) in the DRGs, spinal cord and sciatic nerve and thalamus in naïve mice and 7 days after Spared sciatic Nerve Injury (SNI) in control mice (Hif1α-flfl) and in mice with a specific deletion of hypoxia inducible factor 1 alpha (SNS-HIF1α−/−) in DRG neurons. The sciatic nerves were immunostained for the respective redoxins and counterstained with hematoxylin. The redoxin immunoreactivity was quantified with ImageJ. For the DRGs and spinal cord the data show the quantitative assessment of the intensity of redoxin immunoreactivity transformed to rainbow pseudocolors. In addition, some redoxin examples of the ipsi and contralateral dorsal and ventral horns of the lumbar spinal cord and some redoxin examples of the thalamus are presented. PMID:26693520

  5. Nanofibrous nerve conduits for repair of 30-mm-long sciatic nerve defects

    PubMed Central

    Biazar, Esmaeil; Keshel, Saeed Heidari; Pouya, Majid; Rad, Hadi; Nava, Melody Omrani; Azarbakhsh, Mohammad; Hooshmand, Shirin

    2013-01-01

    It has been confirmed that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve defects needs to be assessed. In this study, we used a nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit to bridge a 30-mm-long gap in the rat sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were cally observed and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There were Schwann cells and glial cells in the regenerated nerves. Masson's trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cells on the operated side of rats. These findings suggest that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit is suitable for repair of long-segment sciatic nerve defects. PMID:25206536

  6. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury.

    PubMed

    Zhao, Qun; Li, Zhi-Yue; Zhang, Ze-Peng; Mo, Zhou-Yun; Chen, Shi-Jie; Xiang, Si-Yu; Zhang, Qing-Shan; Xue, Min

    2015-09-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

  7. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury

    PubMed Central

    Zhao, Qun; Li, Zhi-yue; Zhang, Ze-peng; Mo, Zhou-yun; Chen, Shi-jie; Xiang, Si-yu; Zhang, Qing-shan; Xue, Min

    2015-01-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury. PMID:26604912

  8. Electrophysiology and ultrastructural changes in mouse sciatic nerve associated with colistin sulfate exposure.

    PubMed

    Dai, Chongshan; Li, Jichang; Lin, Wei; Li, Guangxing; Sun, Meicheng; Wang, Fengxia; Li, Jian

    2012-10-01

    To investigate the neurotoxicity of colistin, female mice received colistin sulfate (7.5 mg/kg/12 h) intravenously for 7 days successively, the behavioral changes, and the neuropathological and electrophysiological characterizations of sciatic nerves were determined prior to administration and at 1, 3, 7 and 15 days thereafter. At 1, 3, and 7 days, the compound action potential durations (CAPDs), compound muscle action potential amplitudes (CAPAs), conduction velocities of sciatic-tibial nerve (NCVs) showed progressively abnormal changes with the time prolonged. Compared to the control, these changes were significant at day 7 (p < 0.01, p < 0.05, p < 0.05, p < 0.01 and p < 0.05, respectively), but at day 15, only CAPAs were significantly different (p < 0.05), other indexes presented a recovery tendency. These functional damages were confirmed by the synchronous ultrastructural observations which expressed axonal degeneration and demyelination in the sciatic nerves. These results indicated that peripheral neurotoxicity occurred in mice treated intravenously with colistin sulfate and the electrophysiological and ultrastructural changes of their sciatic nerves exerted in time-dependent fashion.

  9. Viscoelasticity of repaired sciatic nerve by poly(lactic-co-glycolic acid) tubes.

    PubMed

    Piao, Chengdong; Li, Peng; Liu, Guangyao; Yang, Kun

    2013-11-25

    Medical-grade synthetic poly(lactic-co-glycolic acid) polymer can be used as a biomaterial for nerve repair because of its good biocompatibility, biodegradability and adjustable degradation rate. The stress relaxation and creep properties of peripheral nerve can be greatly improved by repair with poly(lactic-co-glycolic acid) tubes. Ten sciatic nerve specimens were harvested from fresh corpses within 24 hours of death, and were prepared into sciatic nerve injury models by creating a 10 mm defect in each specimen. Defects were repaired by anastomosis with nerve autografts and poly(lactic-co-glycolic acid) tubes. Stress relaxation and creep testing showed that at 7 200 seconds, the sciatic nerve anastomosed by poly(lactic-co-glycolic acid) tubes exhibited a greater decrease in stress and increase in strain than those anastomosed by nerve autografts. These findings suggest that poly(lactic-co-glycolic acid) exhibits good viscoelasticity to meet the biomechanical require-ments for a biomaterial used to repair sciatic nerve injury.

  10. Dexamethasone enhanced functional recovery after sciatic nerve crush injury in rats.

    PubMed

    Feng, Xinhong; Yuan, Wei

    2015-01-01

    Dexamethasone is currently used for the treatment of peripheral nerve injury, but its mechanisms of action are not completely understood. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration. In this study, we observed the effects of various doses of dexamethasone on the functional recovery after sciatic nerve crush injury in a rat model. Motor functional recovery was monitored by walking track analysis and gastrocnemius muscle mass ratio. The myelinated axon number was counted by morphometric analysis. Rats administered dexamethasone by local intramuscular injection had a higher nerve function index value, increased gastrocnemius muscle mass ratio, reduced Wallerian degeneration severity, and enhanced regenerated myelinated nerve fibers. Immunohistochemical analysis was performed for CD3 expression, which is a marker for T-cell activation, and infiltration in the sciatic nerve. Dexamethasone-injected rats had fewer CD3-positive cells compared to controls. Furthermore, we found increased expression of GAP-43, which is a factor associated with development and plasticity of the nervous system, in rat nerves receiving dexamethasone. These results provide strong evidence that dexamethasone enhances sciatic nerve regeneration and function recovery in a rat model of sciatic nerve injury through immunosuppressive and potential neurotrophic effects.

  11. Peripheral nerve regeneration following transection injury to rat sciatic nerve by local application of adrenocorticotropic hormone.

    PubMed

    Mohammadi, Rahim; Yadegarazadi, Mohammad-Javad; Amini, Keyvan

    2014-09-01

    The objective of this study was to assess local effect of adrenocorticotropic hormone (ACTH) on the functional recovery of the sciatic nerve in a transection model. Sixty male healthy white Wistar rats were randomized into four experimental groups of 15 animals each: In the sham-operated group (SHAM), the sciatic nerve was exposed and manipulated. In the transected group (TC), the left sciatic nerve was transected and the cut nerve ends were fixed in the adjacent muscle. In the silicone graft group (SIL) a 10-mm defect was made and bridged using a silicone tube. The graft was filled with phosphated-buffer saline alone. In the treatment group a silicone tube (SIL/ACTH) was filled with 10 μL ACTH (0.1 mg/mL). Each group was subdivided into three subgroups of five animals each and regenerated nerve fibres were studied at 4, 8 and 12 weeks post operation. Behavioral testing, functional, gastrocnemius muscle mass and morphometric indices showed earlier regeneration of axons in SIL/ACTH than in SIL group (p < 0.05). Immunohistochemistry clearly showed more positive location of reactions to S-100 in SIL/ACTH than in SIL group. ACTH improved functional recovery and morphometric indices of sciatic nerve. This finding supports role of ACTH after peripheral nerve repair and may have clinical implications for the surgical management of patients after nerve transection.

  12. The Spatial Relationship and Surface Projection of Canine Sciatic Nerve and Sacrotuberous Ligament: A Perineal Hernia Repair Perspective

    PubMed Central

    Khatri-Chhetri, Nabin; Khatri-Chhetri, Rupak; Chung, Cheng-Shu; Chern, Rey-Shyong; Chien, Chi-Hsien

    2016-01-01

    Sciatic nerve entrapment can occur as post-operative complication of perineal hernia repair when sacrotuberous ligament is incorporated during hernia deficit closure. This results in sciatic sensory loss and paralysis of the hind leg. This study investigated the spatial relationship of sciatic nerve and sacrotuberous ligament and their surface topographic projection of 68 cadavers (29 Beagles and 39 Taiwanese mongrels) with various heights (25–56 cm). By gross dissection, the sacrotuberous ligament and sciatic nerve were exposed and their distance in between was measured along four parts (A, B, C, D) of sacrotuberous ligament. The present study revealed that the C was the section of sacrotuberous ligament where the sciatic nerve and the sacrotuberous ligament are closest to each other. Furthermore, a positive correlation was observed between C and height of the dogs. From the present study, we found that the C in smaller dogs has the shortest distance between the sciatic nerve and the sacrotuberous ligament, and thus the most vulnerable to sciatic nerve entrapment, and needs to be avoided or approached cautiously during perineal hernia repair. PMID:27003911

  13. Do all neuropathy patients need an EMG at least once?

    PubMed

    Smith, A Gordon

    2014-10-01

    EMG, which consists of nerve conduction studies and needle electromyography, is an essential diagnostic tool in the evaluation of patients with suspected peripheral neuropathy. Many neurologists order an EMG for all patients with suspected peripheral neuropathy. Not surprisingly, evidence now exists that shows EMG is a major driver of health care costs associated with neuropathy diagnoses. As neurologic practice evolves from fee for service to value-based compensation, neurologists will need to justify the diagnostic utility of EMG (outcome) relative to its cost. While carefully performed studies of diagnostic utility in many patient populations are lacking, a robust literature provides guidance regarding the potential role and limitations of EMG in neuropathy diagnosis as well as the pitfalls referring providers and electrodiagnostic consultants must consider. Do all neuropathy patients need an EMG at least once? This article attempts to answer this question using an illustrative case to highlight critical factors every neurologist must consider before ordering an EMG for neuropathy diagnosis.

  14. US-Guided Femoral and Sciatic Nerve Blocks for Analgesia During Endovenous Laser Ablation

    SciTech Connect

    Yilmaz, Saim Ceken, Kagan; Alimoglu, Emel; Sindel, Timur

    2013-02-15

    Endovenous laser ablation may be associated with significant pain when performed under standard local tumescent anesthesia. The purpose of this study was to investigate the efficacy of femoral and sciatic nerve blocks for analgesia during endovenous ablation in patients with lower extremity venous insufficiency. During a 28-month period, ultrasound-guided femoral or sciatic nerve blocks were performed to provide analgesia during endovenous laser ablation in 506 legs and 307 patients. The femoral block (n = 402) was performed at the level of the inguinal ligament, and the sciatic block at the posterior midthigh (n = 124), by injecting a diluted lidocaine solution under ultrasound guidance. After the blocks, endovenous laser ablations and other treatments (phlebectomy or foam sclerotherapy) were performed in the standard fashion. After the procedures, a visual analogue pain scale (1-10) was used for pain assessment. After the blocks, pain scores were 0 or 1 (no pain) in 240 legs, 2 or 3 (uncomfortable) in 225 legs, and 4 or 5 (annoying) in 41 legs. Patients never experienced any pain higher than score 5. The statistical analysis revealed no significant difference between the pain scores of the right leg versus the left leg (p = 0.321) and between the pain scores after the femoral versus sciatic block (p = 0.7). Ultrasound-guided femoral and sciatic nerve blocks may provide considerable reduction of pain during endovenous laser and other treatments, such as ambulatory phlebectomy and foam sclerotherapy. They may make these procedures more comfortable for the patient and easier for the operator.

  15. Variations of the sciatic nerve anatomy and blood supply in the gluteal region: a review of the literature.

    PubMed

    Kanawati, Andrew James

    2014-11-01

    Variations of the sciatic nerve anatomy and blood supply are complex and largely not dealt with in common anatomy texts. Variations of the sciatic nerve anatomy can be divided into the height of division of its branches, relation of the branches to the piriformis muscle, and its blood supply. These variations should be well known to any surgeon operating in this anatomical region. It is unknown whether these variations increase the risk of surgical injury and consequent morbidity. This paper will review the current knowledge regarding anatomical variations of the sciatic nerve and its blood supply.

  16. Intravenous Lidocaine Infusion to Treat Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

    Papapetrou, Peter; Kumar, Aashish J; Muppuri, Rudram; Chakrabortty, Shushovan

    2015-11-01

    Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. Numerous chemoprotective agents and treatments have been used with limited success to treat chemotherapy-induced peripheral neuropathy. We report a case in which a patient presenting with chemotherapy-induced peripheral neuropathy received an IV lidocaine infusion over the course of 60 minutes with complete symptomatic pain relief for a prolonged period of 2 weeks.

  17. 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.

  18. Glucose intolerance, metabolic syndrome, and neuropathy.

    PubMed

    Cortez, Melissa; Singleton, J Robinson; Smith, A Gordon

    2014-01-01

    There is increasing evidence that impaired glucose tolerance (IGT) or metabolic syndrome may result in peripheral nerve injury, although the exact relationship between the conditions is still being characterized. There is animal model, epidemiologic, and clinical evidence to suggest a pathophysiologic relationship between neuropathy and metabolic syndrome, along with its components including obesity, dyslipidemia, and insulin resistance. IGT and metabolic syndrome are associated with subclinical nerve damage or are typically painful and sensory predominant, although autonomic involvement may also occur. Because there is often preferential small fiber injury and nerve conduction studies may be relatively insensitive, skin biopsy with assessment of intraepidermal nerve fiber density is often used to confirm the diagnosis. Treatment of metabolic syndrome and IGT-associated neuropathies should include diet and exercise counseling, maintenance of normoglycemia, and targeted pharmacologic therapy for modifiable risk factors. Further research is required to fully elucidate the complex pathophysiology, as well as identify optimal diagnostic and treatment approaches.

  19. Bilateral Retrobulbar Optic Neuropathy Associated With Golimumab.

    PubMed

    de Frutos-Lezaun, Marta; Bidaguren, Aritz; de la Riva, Patricia; Meneses, Carlos F; Olascoaga, Javier

    2017-03-09

    We report the first documented case of retrobulbar optic neuropathy associated with golimumab. A 48-year-old man was admitted with a 3-week history of progressive visual loss of his left eye. He had received a second infusion of golimumab for ankylosing spondylitis 10 days before admission. A magnetic resonance imaging scan showed enhancement of both optic nerves and visual evoked potentials were consistent with demyelinating bilateral optic neuropathy, although visual acuity drop in the right eye could not be determined because of deep amblyopia. No improvement was observed after golimumab dechallenge or corticosteroid treatment. Demyelinating complications related to treatment with tumor necrosis factor alpha inhibitors (TNFAI) have been previously described. Golimumab, a fully human monoclonal antibody, is the most recently developed TNFAI and thus, fewer adverse effects have been reported. Further studies should be developed to elucidate if variability in golimumab's pharmacokinetics or TNF receptor binding affinity could explain different safety profiles compared with other TNFAI.

  20. The rare ethambutol-induced optic neuropathy

    PubMed Central

    Song, Wei; Si, Shancheng

    2017-01-01

    Abstract Rationale: Ethambutol-induced optic neuropathy (EON) is a well-known complication that results from the use of ethambutol. The ocular manifestations of EON include painless loss of central vision and cecocentral scotomas in the visual field. Patient concerns: A 75-year-old Chinese Han man suffered from this rare ocular disorder because he took ethambutol for about 8 months. Diagnoses: He was diagnosed as EON based on series of ophthalmic examinations performed. Interventions: Since he has stopped taking this drug for 3 months, we just offered some neurotrophic agents to him. Outcomes: One month later, he came back for return visit. The ophthalmic examinations indicated recovery of the visual function very well. Lessons: The EON is a reversible optic neuropathy if the ocular toxicity is monitored closely among the tuberculosis patients that take ethambutol. PMID:28079833

  1. Postirradiation optic neuropathy in antral carcinoma

    SciTech Connect

    Singh, J.; Vashist, S.

    1984-06-01

    A case is described of a patient who developed radiation-induced optic neuropathy 18 months following cobalt-60 irradiation for carcinoma of the left maxillary antrum and ethmoid sinus. This case is unusual because of the early onset of the optic nerve damage following radiation therapy and the ultimate emergence of the eye involved by tumor compression as the better eye in terms of visual acuity.

  2. 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

  3. Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management.

    PubMed

    Watson, James C; Dyck, P James B

    2015-07-01

    Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy.

  4. Obesity and Hyperlipidemia are Risk Factors for Early Diabetic Neuropathy

    PubMed Central

    Smith, A. Gordon; Singleton, J. Robinson

    2013-01-01

    The Utah Diabetic Neuropathy Study (UDNS) examined 218 type 2 diabetic subjects without neuropathy symptoms, or with symptoms of < 5 years, in order to evaluate risk factors for neuropathy development. Each subject completed symptom questionnaires, the Utah Early Neuropathy Scale (UENS), nerve conduction studies (NCS), quantitative sensory testing (QST) for vibration and cold detection, quantitative sudomotor axon reflex testing (QSART), and skin biopsy with measurement of intraepidermal nerve fiber density (IENFD). Those with abnormalities of ≥ 3 were classified as having probable, and those with 1–2 as possible neuropathy. The relationship between glycemic control, lipid parameters (high density lipoprotein and triglyceride levels), blood pressure, and obesity, and neuropathy risk was examined. There was a significant relationship between the number of abnormalities among these features and neuropathy status (p<0.01). Hypertriglyceridemia, obesity and 3 or more abnormalities increased neuropathy risk (risk ratios 2.1 p<0.03, 2.9 p>0.02 and 3.0 p<0.004 respectively). Multivariate analysis found obesity and triglycerides were related to loss of small unmyelinated axons based on IENFD whereas elevated hemoglobin A1c was related to large myelinated fiber loss (motor conduction velocity). These findings indicate obesity and hypertriglyceridemia significantly increase risk for peripheral neuropathy, independent of glucose control. Obesity/hypertriglyceridemia and hyperglycemia may have differential effects on small versus large fibers. PMID:23731827

  5. Obesity and hyperlipidemia are risk factors for early diabetic neuropathy.

    PubMed

    Smith, A Gordon; Singleton, J Robinson

    2013-01-01

    The Utah Diabetic Neuropathy Study (UDNS) examined 218 type 2 diabetic subjects without neuropathy symptoms, or with symptoms of<5 years, in order to evaluate risk factors for neuropathy development. Each subject completed symptom questionnaires, the Utah Early Neuropathy Scale (UENS), nerve conduction studies (NCS), quantitative sensory testing (QST) for vibration and cold detection, quantitative sudomotor axon reflex testing (QSART), and skin biopsy with measurement of intraepidermal nerve fiber density (IENFD). Those with abnormalities of≥3 were classified as having probable, and those with 1-2 as possible neuropathy. The relationship between glycemic control, lipid parameters (high density lipoprotein and triglyceride levels), blood pressure, and obesity, and neuropathy risk was examined. There was a significant relationship between the number of abnormalities among these features and neuropathy status (p<0.01). Hypertriglyceridemia, obesity and 3 or more abnormalities increased neuropathy risk (risk ratios 2.1 p<0.03, 2.9 p>0.02 and 3.0 p<0.004 respectively). Multivariate analysis found obesity and triglycerides were related to loss of small unmyelinated axons based on IENFD whereas elevated hemoglobin A1c was related to large myelinated fiber loss (motor conduction velocity). These findings indicate obesity and hypertriglyceridemia significantly increase risk for peripheral neuropathy, independent of glucose control. Obesity/hypertriglyceridemia and hyperglycemia may have differential effects on small versus large fibers.

  6. 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.

  7. Chemotherapy-induced neuropathy: A comprehensive survey.

    PubMed

    Miltenburg, N C; Boogerd, W

    2014-08-01

    Chemotherapy induced peripheral neuropathy (CIPN) is a potentially dose limiting side effect of commonly used chemotherapeutic agents like taxanes, vinca-alkaloids, platinum compounds, bortezomib and thalidomide. Supposed pathogenetic mechanisms of CIPN are axonopathy through dying back axon damage and neuronopathy in which the cell bodies of the dorsal root ganglia are involved. The exact pathophysiology however is not clear and different underlying mechanisms have been proposed for different classes of anti-cancer drugs. Sensory symptoms, like pain, numbness and tingling are most common, but motor weakness, autonomic dysfunction and even cranial nerve involvement may occur. CIPN can be painful and/or disabling, causing significant loss of functional abilities and decreasing quality of life. This can lead to dose reductions, discontinuation of treatment and may thus, ultimately, affect survival. Risk factors for CIPN include dose per cycle, cumulative dose, treatment schedule, duration of infusion, administration of other chemotherapeutics, comorbidity and pre-existing peripheral neuropathy. The exploration of polymorphisms in genes associated with incidence or severity of neuropathy might result in identifying individuals being at higher risk of neurotoxicity. An update on genes possibly associated with CIPN is given. CIPN may be reversible or be more or less permanent. Many preventive and treatment strategies have been explored, without significant efficacy up till now. In this review we describe the different drug-related characteristics of CIPN, pharmacogenomic studies, neurophysiological findings, treatment and outcome, and neuroprotective strategies.

  8. Curcumin derivatives promote Schwann cell differentiation and improve neuropathy in R98C CMT1B mice.

    PubMed

    Patzkó, Agnes; Bai, Yunhong; Saporta, Mario A; Katona, István; Wu, Xingyao; Vizzuso, Domenica; Feltri, M Laura; Wang, Suola; Dillon, Lisa M; Kamholz, John; Kirschner, Daniel; Sarkar, Fazlul H; Wrabetz, Lawrence; Shy, Michael E

    2012-12-01

    Charcot-Marie-Tooth disease type 1B is caused by mutations in myelin protein zero. R98C mice, an authentic model of early onset Charcot-Marie-Tooth disease type 1B, develop neuropathy in part because the misfolded mutant myelin protein zero is retained in the endoplasmic reticulum where it activates the unfolded protein response. Because oral curcumin, a component of the spice turmeric, has been shown to relieve endoplasmic reticulum stress and decrease the activation of the unfolded protein response, we treated R98C mutant mice with daily gastric lavage of curcumin or curcumin derivatives starting at 4 days of age and analysed them for clinical disability, electrophysiological parameters and peripheral nerve morphology. Heterozygous R98C mice treated with curcumin dissolved in sesame oil or phosphatidylcholine curcumin performed as well as wild-type littermates on a rotarod test and had increased numbers of large-diameter axons in their sciatic nerves. Treatment with the latter two compounds also increased compound muscle action potential amplitudes and the innervation of neuromuscular junctions in both heterozygous and homozygous R98C animals, but it did not improve nerve conduction velocity, myelin thickness, G-ratios or myelin period. The expression of c-Jun and suppressed cAMP-inducible POU (SCIP)-transcription factors that inhibit myelination when overexpressed-was also decreased by treatment. Consistent with its role in reducing endoplasmic reticulum stress, treatment with curcumin dissolved in sesame oil or phosphatidylcholine curcumin was associated with decreased X-box binding protein (XBP1) splicing. Taken together, these data demonstrate that treatment with curcumin dissolved in sesame oil or phosphatidylcholine curcumin improves the peripheral neuropathy of R98C mice by alleviating endoplasmic reticulum stress, by reducing the activation of unfolded protein response and by promoting Schwann cell differentiation.

  9. The effect of loco-regional anaesthesia on motor activity induced by direct stimulation of the sciatic nerve in dogs.

    PubMed

    Murdoch, A P; Michou, J N

    2016-03-01

    A prospective, randomised, blinded, case-controlled clinical study was designed using client-owned dogs undergoing unilateral pelvic limb orthopaedic surgery, to determine the effect on induced motor activity by electrical stimulation of the sciatic nerve distal to the site of local anaesthetic administration. Dogs were administered 0.5% bupivacaine either extradurally or via a femoral and transgluteal sciatic electrolocation-guided nerve block prior to pelvic limb surgery. Motor response to electrical stimulation of branches of the sciatic nerve was tested and the minimum current required to induce muscle twitch was recorded prior to bupivacaine administration. Provided sensory blockade had been deemed successful intraoperatively, testing was repeated postoperatively, with each dog acting as its own control. Paired t-tests were performed to compare pre- and postoperative minimum currents. Eleven dogs administered extradural and 11 dogs administered femoral and sciatic perineural bupivacaine were eligible for post-operative testing. All dogs displayed normal motor response to electrical stimulation of the sciatic nerve at both sites tested before and after bupivacaine administration. There was no significant difference in the minimum current required to induce muscle twitch between pre- and post-operative testing (P = 0.31 sciatic site, P = 0.36 peroneal site), nor between the two groups using different loco-regional anaesthetic techniques (minimum P = 0.13). This study shows that stimulation of the sciatic nerve distal to the site of bupivacaine administration induces motor activity, despite adequate sensory blockade. This is relevant in surgical cases where mechanical stimulation of the sciatic nerve might be expected and needs to be recognised to avoid postoperative neurapraxia.

  10. Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

    SciTech Connect

    Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin

    2013-10-18

    Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a

  11. Ultrasonography-guided pulsed radiofrequency of sciatic nerve for the treatment of complex regional pain syndrome Type II

    PubMed Central

    Choi, Yi Hwa; Chang, Dong Jin; Hwang, Woon Suk; Chung, Jin Hwan

    2017-01-01

    Although the major mechanism of complex regional pain syndrome (CRPS) involves dysfunctional central or sympathetic nervous system activation, the peripheral nervous system also contributes significantly to its clinical manifestations. Pulsed radiofrequency (PRF) is a recently developed treatment option for neuropathic pain syndromes. Here, we report a case of CRPS Type II after a femur fracture and sciatic nerve injury, in which the pain was treated successfully with ultrasonography-guided selective sciatic nerve PRF application. PMID:28217060

  12. Low-level laser irradiation improves functional recovery and nerve regeneration in sciatic nerve crush rat injury model.

    PubMed

    Wang, Chau-Zen; Chen, Yi-Jen; Wang, Yan-Hsiung; Yeh, Ming-Long; Huang, Mao-Hsiung; Ho, Mei-Ling; Liang, Jen-I; Chen, Chia-Hsin

    2014-01-01

    The development of noninvasive approaches to facilitate the regeneration of post-traumatic nerve injury is important for clinical rehabilitation. In this study, we investigated the effective dose of noninvasive 808-nm low-level laser therapy (LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley rats were divided into 6 experimental groups: a normal group with or without 808-nm LLLT at 8 J/cm(2) and a sciatic nerve crush injury group with or without 808-nm LLLT at 3, 8 or 15 J/cm(2). Rats were given consecutive transcutaneous LLLT at the crush site and sacrificed 20 days after the crush injury. Functional assessments of nerve regeneration were analyzed using the sciatic functional index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was investigated by measuring the myelin sheath thickness of the sciatic nerve using transmission electron microscopy (TEM) and by analyzing the expression of growth-associated protein 43 (GAP43) in sciatic nerve using western blot and immunofluorescence staining. We found that sciatic-injured rats that were irradiated with LLLT at both 3 and 8 J/cm(2) had significantly improved SFI but that a significant improvement of ROM was only found in rats with LLLT at 8 J/cm(2). Furthermore, the myelin sheath thickness and GAP43 expression levels were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT at 3 and 8 J/cm(2). Taken together, these results suggest that 808-nm LLLT at a low energy density (3 J/cm(2) and 8 J/cm(2)) is capable of enhancing sciatic nerve regeneration following a crush injury.

  13. [Multifocal-motor neuropathy and motor neuropathy with multifocal conduction block (Lewis-Sumner syndrome)].

    PubMed

    Finsterer, J; Mamoli, B

    1995-01-01

    Multifocal motor neuropathy, which mimics lower motor neuron disease, is a rare and curious demyelinating neuropathy characterised by slowly progressive, asymmetric limb weakness within the distribution of individual peripheral nerves, wasting, cramps, fasciculations and rare sensory involvement, but without upper motor neuron signs. The cardinal feature and primary pathophysiological basis for the weakness is the multifocal motor conduction block which remains stable for years at the same site and is confined to motor axons. It is defined as > 50% reduction in both the CMAP and the negative peak area on proximal stimulation, as compared with the distal stimulus response without any change in the negative peak duration. Nerves at the site of the conduction block show demyelination, endoneural edema, rudimentary onion bulbs and lymphocytic inflammation. Sensory nerves may show mild demyelination, axon loss and lymphocytic inflammation. The majority of patients shows elevated titers of anti-glycolipid antibodies, which may block the Na+ channels, produce demyelination or interfere with remyelination. However, their role in the pathogenesis of multifocal motor neuropathy remains uncertain. Multifocal motor neuropathy is regarded as the predominantly motor variant of chronic inflammatory demyelinating polyneuropathy and can be treated best with immunoglobulins and cyclophosphamide.

  14. Ischemic neuropathy and rhabdomyolysis as presenting symptoms of postpartum cardiomyopathy.

    PubMed

    Helmich, Rick C G; van Laarhoven, Hanneke W M; Schoonderwaldt, Hennie C; Janssen, Mirian C H

    2009-05-01

    Rhabdomyolysis and peripheral neuropathy are two distinct disease entities which are rarely encountered in combination. We present a woman with rhabdomyolysis and peripheral neuropathy 3 weeks postpartum. Her symptoms were caused by bilateral femoral artery thrombosis due to postpartum cardiomyopathy (PPCM). This demonstrates that PPCM may present with predominantly non-cardial symptoms and underscores the importance of rapidly recognizing this disorder.

  15. Quality assessment of online patient education resources for peripheral neuropathy.

    PubMed

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

    2013-03-01

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

  16. Compressive femoral neuropathy: a rare complication of anticoagulation.

    PubMed

    Ong, H S

    2007-03-01

    The most common coagulation disorder associated with warfarin use is bleeding, but compressive femoral neuropathy is an unusual presentation. A 63-year-old man with compressive femoral neuropathy from an iliacus haematoma is reported. The diagnosis was confirmed on magnetic resonance imaging and treated conservatively with good clinical response and radiological evidence of resolution.

  17. Peripheral insensate neuropathy--a tall problem for US adults?

    PubMed

    Cheng, Yiling J; Gregg, Edward W; Kahn, Henry S; Williams, Desmond E; De Rekeneire, Nathalie; Narayan, K M Venkat

    2006-11-01

    The relation between height and lower extremity peripheral insensate neuropathy among persons with and without diabetes was examined by use of the 1999-2002 US National Health and Nutrition Examination Survey with 5,229 subjects aged 40 or more years. A monofilament was used to determine whether any of three areas on each foot were insensate. Peripheral insensate neuropathy was defined as the presence of one or more insensate areas. Its prevalence was nearly twice as high among persons with diabetes (21.2%) as among those without diabetes (11.5%; p < 0.001). Men (16.2%) had 1.7 times the prevalence of peripheral insensate neuropathy as did women (9.4%), but the difference was not significant after adjustment for height. Greater height was associated with increased peripheral insensate neuropathy prevalence among persons with and without diabetes (p < 0.001). This association was characterized by a sharp increase in prevalence among persons who were taller than 175.5 cm. Peripheral insensate neuropathy risk was significantly higher among those taller than 175.5 cm (adjusted odds ratio = 2.3, 95% confidence interval: 1.5, 3.5). The authors conclude that body height is an important correlate of peripheral insensate neuropathy. This association largely accounts for the difference in peripheral insensate neuropathy prevalence between men and women. Height may help health-care providers to identify persons at high risk of peripheral insensate neuropathy.

  18. [Bilateral ischemic optic neuropathy secondary to acute ergotism].

    PubMed

    Sommer, S; Delemazure, B; Wagner, M; Xenard, L; Rozot, P

    1998-02-01

    We report a case of a 31 year-old man who presented a bilateral ischemic optic neuropathy associated with headaches and severe systemic hypertension. This episode appeared after administration of ergotamine tartrate and macrolides. This medication probably led to a vasospasm which occurs in patients with hypertension. The cardiovascular and serum lipid evaluations were normal. A migraine optic neuropathy can be evoked.

  19. Protective effect of amifostine against cisplatin-induced motor neuropathy in rat.

    PubMed

    Yalcin, Suayib; Nurlu, Gulay; Orhan, Bülent; Zeybek, Dilara; Müftüoğlu, Sevda; Sarer, Banu; Yildirim, Berna Akkuş; Cetin, Eren

    2003-01-01

    Cisplatin (CDDP) is a potent anticancer drug. Neurotoxicity is one of the most important dose-limiting toxicity of CDDP. We investigated the role of amifostine in the protection against CDDP-induced neurotoxicity especially on the motor nerves. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to two groups, each including six rats. Group A received CDDP plus amifostine and Group B received CDDP only. Electroneurography (ENG) was carried out in the beginning and at the end of 7 wk; then, the rats were sacrificed and the sciatic nerve was removed for histopathological examination. The mean initial latency was 2.4667 msn for group A and 2.44833 msn for group B. After 7 wk of treatment, the latency was 2.9167 for group A and 2.6333 for group B. The difference in latencies was not statistically significant. The amplitude was 11.7853 mV and 13.533 mV for groups A and B, respectively. After 7 wk of treatment, the amplitude was 9.400 mV and 9.000 mV, respectively. The decrease of amplitude in compound muscle action potential (CMAP) was 20% in the amifostine group and the decrease was 33% in the untreated group. The mean area of the CMAP in group A was 9.400 mVsn initially and 9.666 mVsn at the end of the treatment; there was a 0.3% increase despite CDDP treatment. In group B, the mean area of the CMAP was 13.816 mVsn initially and 11.857 mVsn at the end of the treatment; this corresponded to a statistically significant 14% decrease as a result of CDDP treatment. The ENG and histopathological studies showed that at the given dose and schedule CDDP-induced motor neuropathy and amifostine reduced this neuropathy both by protection of the amplitude and area of the CMAP in ENG studies and by sparing a larger number of nerve fibers.

  20. Longitudinal study of intraneural perineurioma--a benign, focal hypertrophic neuropathy of youth.

    PubMed

    Mauermann, Michelle L; Amrami, Kimberly K; Kuntz, Nancy L; Spinner, Robert J; Dyck, Peter J; Bosch, E Peter; Engelstad, Janean; Felmlee, Joel P; Dyck, P James B

    2009-08-01

    The natural history of intraneural perineurioma has been inadequately studied. The aim of this study was to characterize the clinical presentation, electrophysiologic and imaging features and outcome of intraneural perineurioma. We ask if intraneural perineurioma is a pure motor syndrome that remains confined to one nerve and should be treated by surgical resection. We examined the nerve biopsies of cases labelled perineurioma and selected those with diagnostic features. Thirty-two patients were identified; 16 children and 16 adults; 16 males and 16 females. Median age of onset of neurological symptoms was 14 years (range 0.5-55 years) and median age at evaluation was 17 years (range 2-56 years). All patients had motor deficits; however, mild sensory symptoms or signs were experienced by 27 patients; 'prickling' or 'asleep numbness' in 20, mild pain in 13 and sensory loss in 23. The sciatic nerve or its branches was most commonly affected in 15, followed by brachial plexus, radial nerve and ulnar nerve (four each). Magnetic resonance imaging demonstrated nerve enlargement (29/32), T1 isointensity (27/32), T2 hyperintensity (25/32) and contrast enhancement (20/20). Diagnoses were made based on targeted biopsy of the focal nerve enlargement identified by imaging. Neurological impairment was of a moderate severity (median Neuropathy Impairment Score was 12 points, range 2-49 points). All patients had focal involvement with 27 involving one nerve and five involving a plexus (one bilateral). Long-term follow-up was possible by telephone interview for 23 patients (median 36 months, range 2-177 months). Twelve patients also had follow-up neurologic evaluation (median 45 months, range 10-247 months). The median Neuropathy Impairment Score had changed from 12.6 to 15.4 points (P = 0.19). In all cases, the distribution of neurologic findings remained unchanged. Median Dyck Disability Score was 3 (range 2-5) indicating a mild impairment without interfering with activities of

  1. 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

  2. Diagnosis and treatment of pain in small-fiber neuropathy.

    PubMed

    Hovaguimian, Alexandra; Gibbons, Christopher H

    2011-06-01

    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 proposes 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.

  3. Purple pigments: the pathophysiology of acute porphyric neuropathy.

    PubMed

    Lin, Cindy S-Y; Lee, Ming-Jen; Park, Susanna B; Kiernan, Matthew C

    2011-12-01

    The porphyrias are inherited metabolic disorders arising from disturbance in the haem biosynthesis pathway. The neuropathy associated with acute intermittent porphyria (AIP) occurs due to mutation involving the enzyme porphobilinogen deaminase (PBGD) and is characterised by motor-predominant features. Definitive diagnosis often encompasses a combination of biochemical, enzyme analysis and genetic testing, with clinical neurophysiological findings of a predominantly motor axonal neuropathy. Symptomatic and supportive treatment are the mainstays during an acute attack. If administered early, intravenous haemin may prevent progression of neuropathy. While the pathophysiology of AIP neuropathy remains unclear, axonal dysfunction appears intrinsically linked to the effects of neural energy deficits acquired through haem deficiency coupled to the neurotoxic effects of porphyrin precursors. The present review will provide an overview of AIP neuropathy, including discussion of recent advances in understanding developed through neurophysiological approaches that have further delineated the pathophysiology of axonal degeneration.

  4. 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

  5. [Pyrimidal syndrome and anatomical variations as a cause of insidious sciatic pain].

    PubMed

    Ortiz Sánchez, V E; Charco Roca, L M; Soria Quiles, A; Zafrilla Disla, E; Hernandez Mira, F

    2014-11-01

    The case is presented of a 42 year old woman who had been suffering a loss of strength in her left leg for six years. After an extensive diagnostic study, the pain was classified as of functional origin by a diagnosis of exclusion. Since then, the patient has tried all kind of drug treatments and conservative techniques without improvement. After an exhaustive study with inconclusive results, the case was discussed with the Orthopaedics Department, who performed an exploratory surgery, in which compression of the sciatic nerve due to an anatomical variation of the piriformis muscle was observed. Part of the muscle was resected during surgery and the sciatic nerve was freed, after which the patient experienced a great improvement.

  6. [Application of direct long-standing electrostimulation in consequences of the sciatic nerve injury].

    PubMed

    Tsymbaliuk, Iu V

    2013-04-01

    The results of surgical treatment of 57 patients, suffering consequences of the sciatic nerve injury, using the system for long-lasting electrostimulation "Naysi 3M", were presented. The domestically manufactured system is individual and gives possibility to conduct the direct electrostimulation procedures in the home conditions, several times a day, for a long time. Positive results, consisting of the various degree enhancement of the lower extremities movements volume and strength, the sensitivity restoration and the pain severity reduction or disappearance, were achieved in 46 (81%) patients. In inefficacy of conservative treatment and presence of indications for the operation in patients with sciatic nerve injury the long-lasting electrostimulation secures restoration of the lower extremities lost functions, the pain syndrome and the vegetative-trophic disorders regress.

  7. Berberine Ameliorates Allodynia Induced by Chronic Constriction Injury of the Sciatic Nerve in Rats.

    PubMed

    Kim, Hyun Jee

    2015-08-01

    The objective of this study was to investigate whether berberine could ameliorate allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After inducement of CCI, significant increases in the number of paw lifts from a cold plate test (cold allodynia) and decreased paw withdrawal threshold in the von Frey hair stimulation test (mechanical allodynia) were observed. However, these cold and mechanical allodynia were markedly alleviated by berberine administration in a dose-dependent manner. Sciatic nerve myeloperoxidase and malondialdehyde activities were also attenuated by berberine administration. Continuous injection for 7 days induced no development of tolerance. The antiallodynic effect of 20 mg/kg berberine was comparable to that of amitriptyline 10 mg/kg. This study demonstrated that berberine could mitigate allodynia induced by CCI, a neuropathic pain model, and it suggested that the anti-inflammatory and antioxidative properties of berberine contributed to the antiallodynic effect in the CCI model.

  8. Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy

    PubMed Central

    Sames, Lori; Moore, Allison; Arnold, Renee; Ekins, Sean

    2014-01-01

    Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT) disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN) is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL) assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN) could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF), Hannah's Hope Fund (HHF), The Neuropathy Association (TNA) and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies, we can

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

    PubMed Central

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

    2016-01-01

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

  10. Erythropoietin enhances nerve repair in anti-ganglioside antibody-mediated models of immune neuropathy.

    PubMed

    Zhang, Gang; Lehmann, Helmar C; Bogdanova, Nataliia; Gao, Tong; Zhang, Jiangyang; Sheikh, Kazim A

    2011-01-01

    Guillain-Barré syndrome (GBS) is a monophasic immune neuropathic disorder in which a significant proportion of patients have incomplete recovery. The patients with incomplete recovery almost always have some degree of failure of axon regeneration and target reinnervation. Anti-ganglioside antibodies (Abs) are the most commonly recognized autoimmune markers in all forms of GBS and specific Abs are associated with the slow/poor recovery. We recently demonstrated that specific anti-ganglioside Abs inhibit axonal regeneration and nerve repair in preclinical models by activation of small GTPase RhoA and its downstream effectors. The objective of this study was to determine whether erythropoietin (EPO), a pleiotropic cytokine with neuroprotective and neurotrophic properties, enhances nerve regeneration in preclinical cell culture and animal models of autoimmune neuropathy/nerve repair generated with monoclonal and patient derived Abs. Primary neuronal cultures and a standardized sciatic crush nerve model were used to assess the efficacy of EPO in reversing inhibitory effects of anti-ganglioside Abs on nerve repair. We found that EPO completely reversed the inhibitory effects of anti-ganglioside Abs on axon regeneration in cell culture models and significantly improved nerve regeneration/repair in an animal model. Moreover, EPO-induced proregenerative effects in nerve cells are through EPO receptors and Janus kinase 2/Signal transducer and activator of transcription 5 pathway and not via early direct modulation of small GTPase RhoA. These preclinical studies indicate that EPO is a viable candidate drug to develop further for neuroprotection and enhancing nerve repair in patients with GBS.

  11. Diagnostic Cutoff Value for Ultrasonography of the Common Fibular Neuropathy at the Fibular Head

    PubMed Central

    2016-01-01

    Objective To establish the diagnostic cutoff value of ultrasonographic measurement for common fibular neuropathy (CFN) at the fibular head (FH). Methods Twenty patients with electrodiagnostically diagnosed CFN at the FH and 30 healthy controls were included in the study. The cross-sectional area (CSA) of sciatic nerve at mid-thigh level, common fibular nerve at popliteal fossa (PF), and common fibular (CF) nerve at FH were measured. Additionally, the difference of CF nerve CSA at the FH between symptomatic side and asymptomatic side (ΔSx–Asx), the ratio of CF nerve CSA at FH to at PF (FH/PF), and the ratio of CF nerve CSA at the FH symptomatic side to asymptomatic side (Ratio Sx–Asx) were calculated. Results CSA at the FH, FH/PF, ΔSx–Asx, and Ratio Sx–Asx showed significant differences between the patient and control groups. The cutoff value for diagnosing CFN at the FH was 11.7 mm2 for the CSA at the FH (sensitivity 85.0%, specificity 90.0%), 1.70 mm2 for the ΔSx–Asx (sensitivity 83.3%, specificity 97.0%), 1.11 for the FH/PF (sensitivity 47.1%, specificity 93.3%), and 1.24 for the Ratio Sx–Asx (sensitivity 72.2%, specificity 96.7%). Conclusion The ultrasonographic measurement and cutoff value could be a valuable reference in diagnosing CFN at the FH and improving diagnostic reliability and efficacy. PMID:28119836

  12. Fuzzy expert system for diagnosing diabetic neuropathy

    PubMed Central

    Rahmani Katigari, Meysam; Ayatollahi, Haleh; Malek, Mojtaba; Kamkar Haghighi, Mehran

    2017-01-01

    AIM To design a fuzzy expert system to help detect and diagnose the severity of diabetic neuropathy. METHODS The research was completed in 2014 and consisted of two main phases. In the first phase, the diagnostic parameters were determined based on the literature review and by investigating specialists’ perspectives (n = 8). In the second phase, 244 medical records related to the patients who were visited in an endocrinology and metabolism research centre during the first six months of 2014 and were primarily diagnosed with diabetic neuropathy, were used to test the sensitivity, specificity, and accuracy of the fuzzy expert system. RESULTS The final diagnostic parameters included the duration of diabetes, the score of a symptom examination based on the Michigan questionnaire, the score of a sign examination based on the Michigan questionnaire, the glycolysis haemoglobin level, fasting blood sugar, blood creatinine, and albuminuria. The output variable was the severity of diabetic neuropathy which was shown as a number between zero and 10, had been divided into four categories: absence of the disease, (the degree of severity) mild, moderate, and severe. The interface of the system was designed by ASP.Net (Active Server Pages Network Enabled Technology) and the system function was tested in terms of sensitivity (true positive rate) (89%), specificity (true negative rate) (98%), and accuracy (a proportion of true results, both positive and negative) (93%). CONCLUSION The system designed in this study can help specialists and general practitioners to diagnose the disease more quickly to improve the quality of care for patients. PMID:28265346

  13. Electrophysiological and functional effects of shock waves on the sciatic nerve of rats.

    PubMed

    Wu, Yi-Hui; Liang, Huey-Wen; Chen, Wen-Shiang; Lai, Jin-Shin; Luh, Jer-Junn; Chong, Fok-Ching

    2008-10-01

    Extracorporeal shockwave therapy (ESWT) has been applied in lithotripsy and treatments of musculoskeletal disorders over the past decade, but its effects on peripheral nerves remain unclear. This study investigated the short-term effects of shockwaves on the sciatic nerve of rats. The nerves were surgically exposed and then stimulated with shockwaves at three intensities. We evaluated the motor nerve conduction velocity (MNCV) of treated sciatic nerves before, immediately after (day 0) and at 1, 4, 7 and 14 d after shockwave treatment. Two functional tests-the sciatic functional index and the withdrawal reflex latency-were evaluated before and at 1, 4, 7 and 14 d after shockwave application. The rats were sacrificed on days 0, 1, 4, 7 and 14 for morphologic observation. The degassed treatment group received high-intensity shockwave treatment using degassed normal saline as the contact medium, and MNCV was measured before and on days 0, 1, 4, 7 and 14. The sham group received the same procedure as the treatment groups (i.e., the surgical operation to expose the sciatic nerve) but with no shockwave treatment. The control group received no surgical operation or shockwave treatment. The results showed moderate decrease in the MNCV after shockwave treatment and damage to the myelin sheath of large-diameter myelinated fibers. The effect was largest (reduction to 60.9% of baseline MNCV) and of longest duration (7 to 14 d) in the high-intensity group. There were no significant changes in functional tests. These results indicated that direct application of shockwaves can induce reversible segmental demyelination in large-diameter fibers, with the electrophysiological changes being positively correlated with the intensity of the shockwaves.

  14. The adductor part of the adductor magnus is innervated by both obturator and sciatic nerves.

    PubMed

    Takizawa, Megumi; Suzuki, Daisuke; Ito, Hajime; Fujimiya, Mineko; Uchiyama, Eiichi

    2014-07-01

    The hip adductor group, innervated predominantly by the obturator nerve, occupies a large volume of the lower limb. However, case reports of patients with obturator nerve palsy or denervation have described no more than minimal gait disturbance. Those facts are surprising, given the architectural characteristics of the hip adductors. Our aim was to investigate which regions of the adductor magnus are innervated by the obturator nerve and by which sciatic nerve and to consider the clinical implications. Twenty-one lower limbs were examined from 21 formalin-fixed cadavers, 18 males and 3 females. The adductor magnus was dissected and was divided into four parts (AM1-AM4) based on the locations of the perforating arteries and the adductor hiatus. AM1 was supplied solely by the obturator nerve. AM2, AM3, and AM4 received innervation from both the posterior branch of the obturator nerve and the tibial nerve portion of the sciatic nerve in 2 (9.5%), 20 (95.2%), and 6 (28.6%) of the cadavers, respectively. The double innervation in more than 90% of the AM3s is especially noteworthy. Generally, AM1-AM3 corresponds to the adductor part, traditionally characterized as innervated by the obturator nerve, and AM4 corresponds to the hamstrings part, innervated by the sciatic nerve. Here, we showed that the sciatic nerve supplies not only the hamstrings part but also the adductor part. These two nerves spread more widely than has generally been believed, which could have practical implications for the assessment and treatment of motor disability.

  15. Student Anesthetist Learning Curve Perspectives on Sciatic Nerve Localization Proficiency - A Pilot Study

    DTIC Science & Technology

    2000-10-01

    neuroanatomist experienced with rat anatomy experimentation and the specifics of rodent sciatic nerve anatomy, consisting of a full day of instruction. Greene s...classic text on rat anatomy was researched and studied by the SRNA. Additionally, the SRNA received animal procedures handling approved by the...reviewing rat anatomy from Greene s classic text (1963), and after receiving additional hands-on training from a neuroanatomist familiar with rat anatomy , an

  16. Student Anesthetist Learning Curve Perspectives on Sciatic Nerve Localization Proficiency - A Pilot Study

    DTIC Science & Technology

    2000-10-01

    blockade. The SRNA received training from a neuroanatomist experienced with rat anatomy experimentation and the specifics of rodent sciatic nerve...anatomy, consisting of a full day of instruction. Greene s classic text on rat anatomy was researched and studied by the SRNA. Additionally, the SRNA...investigator. Measurement Methods Initially, after reviewing rat anatomy from Greene s classic text (1963), and after receiving additional hands-on

  17. Gabapentin Treatment for Neuropathic Pain in a Child with Sciatic Nerve Injury

    PubMed Central

    Akkurt, Halil Ekrem; Gümüş, Haluk; Göksu, Hamit; Odabaşı, Ömer Faruk; Yılmaz, Halim

    2015-01-01

    There are a restricted number of studies about usage of gabapentin for neuropathic pain treatment of pediatric patients. We shared a 12-year-old male case with severe neuropathic pain that hindered the rehabilitation programme for the loss of muscle power and movement limitation. Neuropathic pain developed after peripheral sciatic damage due to firearm traumatisation did not respond to other medical treatments but healed nearly completely after gabapentin usage. PMID:26346828

  18. A Combination of Schwann-Cell Grafts and Aerobic Exercise Enhances Sciatic Nerve Regeneration

    PubMed Central

    Souto, Allana; Oliveira, Júlia Teixeira; de Lima, Silmara; Tonda-Turo, Chiara; Marques, Suelen Adriani; de Almeida, Fernanda Martins; Martinez, Ana Maria Blanco

    2014-01-01

    Background Despite the regenerative potential of the peripheral nervous system, severe nerve lesions lead to loss of target-organ innervation, making complete functional recovery a challenge. Few studies have given attention to combining different approaches in order to accelerate the regenerative process. Objective Test the effectiveness of combining Schwann-cells transplantation into a biodegradable conduit, with treadmill training as a therapeutic strategy to improve the outcome of repair after mouse nerve injury. Methods Sciatic nerve transection was performed in adult C57BL/6 mice; the proximal and distal stumps of the nerve were sutured into the conduit. Four groups were analyzed: acellular grafts (DMEM group), Schwann cell grafts (3×105/2 µL; SC group), treadmill training (TMT group), and treadmill training and Schwann cell grafts (TMT + SC group). Locomotor function was assessed weekly by Sciatic Function Index and Global Mobility Test. Animals were anesthetized after eight weeks and dissected for morphological analysis. Results Combined therapies improved nerve regeneration, and increased the number of myelinated fibers and myelin area compared to the DMEM group. Motor recovery was accelerated in the TMT + SC group, which showed significantly better values in sciatic function index and in global mobility test than in the other groups. The TMT + SC group showed increased levels of trophic-factor expression compared to DMEM, contributing to the better functional outcome observed in the former group. The number of neurons in L4 segments was significantly higher in the SC and TMT + SC groups when compared to DMEM group. Counts of dorsal root ganglion sensory neurons revealed that TMT group had a significant increased number of neurons compared to DMEM group, while the SC and TMT + SC groups had a slight but not significant increase in the total number of motor neurons. Conclusion These data provide evidence that this combination of therapeutic strategies can

  19. Anterior ischemic optic neuropathy following dengue fever.

    PubMed

    Ramakrishnan, Reshma; Shrivastava, Saurabh; Deshpande, Shrikant; Patkar, Priyanka

    2016-01-01

    Dengue fever is caused by a flavivirus. This infection is endemic in the tropics and warm temperate regions of the world. Ocular manifestations of dengue fever include subconjunctival, vitreous, and retinal haemorrhages; posterior uveitis; optic neuritis; and maculopathies, haemorrhage, and oedema. However anterior ischemic optic neuropathy is a rare presentation. Optic nerve ischemia most frequently occurs at the optic nerve head, where structural crowding of nerve fibers and reduction of the vascular supply may combine to impair perfusion to a critical degree and produce optic disc oedema. Here we present a case of anterior ischemic optic neurapathy associated with dengue fever.

  20. Molecular Mechanisms of Inherited Demyelinating Neuropathies

    PubMed Central

    SCHERER, STEVEN S.; WRABETZ, LAWRENCE

    2008-01-01

    The past 15 years have witnessed the identification of more than 25 genes responsible for inherited neuropathies in humans, many associated with primary alterations of the myelin sheath. A remarkable body of work in patients, as well as animal and cellular models, has defined the clinical and molecular genetics of these illnesses and shed light on how mutations in associated genes produce the heterogeneity of dysmyelinating and demyelinating phenotypes. Here, we review selected recent developments from work on the molecular mechanisms of these disorders and their implications for treatment strategies. PMID:18803325

  1. Anterior ischemic optic neuropathy following dengue fever

    PubMed Central

    Ramakrishnan, Reshma; Shrivastava, Saurabh; Deshpande, Shrikant; Patkar, Priyanka

    2016-01-01

    Dengue fever is caused by a flavivirus. This infection is endemic in the tropics and warm temperate regions of the world. Ocular manifestations of dengue fever include subconjunctival, vitreous, and retinal haemorrhages; posterior uveitis; optic neuritis; and maculopathies, haemorrhage, and oedema. However anterior ischemic optic neuropathy is a rare presentation. Optic nerve ischemia most frequently occurs at the optic nerve head, where structural crowding of nerve fibers and reduction of the vascular supply may combine to impair perfusion to a critical degree and produce optic disc oedema. Here we present a case of anterior ischemic optic neurapathy associated with dengue fever. PMID:27843231

  2. Histopathologic studies of ischemic optic neuropathy.

    PubMed Central

    Knox, D L; Kerrison, J B; Green, W R

    2000-01-01

    PURPOSE: To define the histopathologic features of eyes in which a pathologic diagnosis of ischemic optic neuropathy had been made in the years 1951 through 1998. METHODS: The following data were documented: age of patient, race, sex, source of tissue, cause of death, clinical history, interval from loss of vision to death, enucleation, exenteration, and biopsy. The histopathologic criteria for diagnosis of ischemic optic neuropathy were the presence of localized ischemic edema, cavernous degeneration, or an area of atrophy located superior or inferior in the optic nerve. Cases with history of abrupt loss of vision were combined with reports from the literature to construct a time table of histopathologic features and associated conditions. RESULTS: Ischemic optic neuropathy was present in 193 eyes. There were 88 females and 65 males. The average age was 71.6 years. Ischemic edema without (early) and with (later) gitter macrophages was present in 26 (13.5%). Cavernous degeneration was present in 69 nerves (36%). Mucopolysaccharide (MPS) was present in 37 cavernous lesions 1 month or longer after loss of vision. Cavernous lesions were seen in 3 eyes in which peripapillary retinal nerve fiber layer hemorrhage had been observed prior to death. Atrophic lesions, the most common pattern, were observed in 133 optic nerves (66.8%). More than 1 ischemic lesion was seen in 38 optic nerves (19.7%). Bilateral ischemic lesions were seen in 50 (35.2%) of 142 paired eyes. CONCLUSIONS: Ischemic optic nerve lesions are initially acellular and later show macrophage infiltration. Cavernous lesions with MPS are present 4 weeks or longer after vision loss. The location of MPS posteriorly and along the internal margin suggests that MPS is produced at the edges of lesions. Progressive vision loss in ischemic optic neuropathy may be secondary to compression of intact nerve from ischemic edema and cavernous swelling, or a second ischemic lesion. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5

  3. Compressive Optic Neuropathy from Allergic Fungal Sinusitis

    PubMed Central

    Tong, Jessica; Jefferson, Niall; Chaganti, Joga; Fraser, Clare L.

    2015-01-01

    ABSTRACT Ophthalmic manifestations of allergic fungal sinusitis (AFS) are rare, but can occur in advanced disease. A 32-year-old man with advanced AFS presented with severe bilateral vision loss and restricted ocular motility. Magnetic resonance imaging and histological analysis confirmed active chronic AFS. Functional endoscopic sinus surgery was performed, with adjunctive steroid therapy. Although AFS is a reasonably well-recognised entity, severe disease causing bilateral visual deficits is rarely encountered. This can confound the diagnosis and appropriate treatment. Ophthalmologists should thus be aware of compressive optic neuropathy as a complication of advanced AFS to prompt early treatment and mitigate visual loss. PMID:27928361

  4. High voltage pulsed current stimulation of the sciatic nerve in rats: analysis by the SFI

    PubMed Central

    Leoni, Anita Sofia Leite; Mazzer, Nilton; Guirro, Rinaldo Roberto de Jesus; Jatte, Fernanda Guadallini; Chereguini, Paulo Augusto Costa; Monte-Raso, Vanessa Vilela

    2012-01-01

    Objective To analyze the efficiency of high voltage pulsed current (HVPC) with early application in three different sites, in the regeneration of the sciatic nerve in rats submitted to crush injury, the sciatic functional index (SFI) was used to assess the functional recovery. Methods After crushing of the nerve, 57 animals were submitted to cathodal HVPC at frequency of 50Hz and voltage of 100V, 20 minutes per day, 5 days per week. The rats were divided into five groups: control group; ganglion group; ganglion + muscle group; muscle group; and sham group. The SFI was determined weekly for seven weeks, from the preoperative period to the 6th postoperative week. Results Compared with the control group, the results showed a significantly better performance of group 2 for the first 3 weeks; group 3 showed significantly better performance in the third week; and group 4 showed a significantly negative performance during the 4th and 6th weeks. Conclusion Early application of HVPC had a positive effect in the treatment of the spinal cord region and the sciatic nerve root ganglion with a dispersive electrode on the contralateral lumbar region or on the gastrocnemius. However, HVPC had a negative effect in the treatment with an active electrode on the gastrocnemius and a dispersive electrode on the contralateral thigh. Level of evidence II, Prospective comparative study. PMID:24453588

  5. Improvement of Sciatic Nerve Regeneration Using Laminin-Binding Human NGF-β

    PubMed Central

    Sun, Wenjie; Sun, Changkai; Zhao, Hui; Lin, Hang; Han, Qianqian; Wang, Jingyu; Ma, Hui; Chen, Bing; Xiao, Zhifeng; Dai, Jianwu

    2009-01-01

    Background Sciatic nerve injuries often cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which finally result in substantial functional loss and decreased quality of life. Nerve growth factor (NGF) plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical applications. We reported here by fusing with the N-terminal domain of agrin (NtA), NGF-β could target to nerve cells and improve nerve regeneration. Methods Laminin-binding assay and sustained release assay of NGF-β fused with NtA (LBD-NGF) from laminin in vitro were carried out. The bioactivity of LBD-NGF on laminin in vitro was also measured. Using the rat sciatic nerve crush injury model, the nerve repair and functional restoration by utilizing LBD-NGF were tested. Findings LBD-NGF could specifically bind to laminin and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that LBD-NGF could be retained and concentrated at the nerve injury sites to promote nerve repair and enhance functional restoration following nerve damages. Conclusion Fused with NtA, NGF-β could bind to laminin specifically. Since laminin is the major component of nerve extracellular matrix, laminin binding NGF could target to nerve cells and improve the repair of peripheral nerve injuries. PMID:19587785

  6. The effect of chick embryo amniotic fluid on sciatic nerve regeneration of rats

    PubMed Central

    Farjah, Gh. H.; Fazli, F.

    2015-01-01

    The purpose of this experimental study was to evaluate the effect of chicken amniotic fluid (AF) on a cross section of rat sciatic nerves. Thirty adult male Sprague-Dawley rats weighing 275 to 300 g, were randomized into three groups treated with (1) amniotic fluid or AF (n=10), (2) normal saline or NS (n=10), and (3) sham surgery (n=10). The AF was aspirated from the amniotic cavity of incubating chick embryos at day 14. The sciatic nerve was exposed and sharply transected. Immediate epineurial repair was then performed. AF treated animals were given 2 ml/kg of the chick embryo AF subcutaneously, once daily, five times a week for up to 2 weeks. All animals were evaluated by sciatic functional index (SFI), electrophysiology, histology, and immunohistochemistry at days 28 and 56 after surgery. The SFI difference between AF and NS groups at days 21 and 28 after operation was statistically significant (P<0.05). The number of myelinated fibers in the AF group was significantly greater than that of the NS group at day 28 (P<0.05). At days 28 and 56 after operation, the nerve conduction velocity (NCV) mean of the AF group was faster than that of the NS group, but the difference was not statistically significant (P>0.05). The results of this study demonstrate that chick AF can enhance peripheral nerve regeneration. PMID:27175170

  7. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

    PubMed Central

    Kim, Joo Wan; Ku, Sae-Kwang; Kim, Ki Young; Kim, Sung Goo; Han, Min Ho; Kim, Gi-Young; Hwang, Hye Jin; Kim, Byung Woo; Kim, Cheol Min

    2015-01-01

    The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation. PMID:26064425

  8. Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair and Hindlimb Transplant Model

    PubMed Central

    Cooney, Damon S.; Wimmers, Eric G.; Ibrahim, Zuhaib; Grahammer, Johanna; Christensen, Joani M.; Brat, Gabriel A.; Wu, Lehao W.; Sarhane, Karim A.; Lopez, Joseph; Wallner, Christoph; Furtmüller, Georg J.; Yuan, Nance; Pang, John; Sarkar, Kakali; Lee, W. P. Andrew; Brandacher, Gerald

    2016-01-01

    This study investigates the efficacy of local and intravenous mesenchymal stem cell (MSC) administration to augment neuroregeneration in both a sciatic nerve cut-and-repair and rat hindlimb transplant model. Bone marrow-derived MSCs were harvested and purified from Brown-Norway (BN) rats. Sciatic nerve transections and repairs were performed in three groups of Lewis (LEW) rats: negative controls (n = 4), local MSCs (epineural) injection (n = 4), and systemic MSCs (intravenous) injection (n = 4). Syngeneic (LEW-LEW) (n = 4) and allogeneic (BN-LEW) (n = 4) hindlimb transplants were performed and assessed for neuroregeneration after local or systemic MSC treatment. Rats undergoing sciatic nerve cut-and-repair and treated with either local or systemic injection of MSCs had significant improvement in the speed of recovery of compound muscle action potential amplitudes and axon counts when compared with negative controls. Similarly, rats undergoing allogeneic hindlimb transplants treated with local injection of MSCs exhibited significantly increased axon counts. Similarly, systemic MSC treatment resulted in improved nerve regeneration following allogeneic hindlimb transplants. Systemic administration had a more pronounced effect on electromotor recovery while local injection was more effective at increasing fiber counts, suggesting different targets of action. Local and systemic MSC injections significantly improve the pace and degree of nerve regeneration after nerve injury and hindlimb transplantation. PMID:27510321

  9. 2,4-Dinitrophenol blocks neurodegeneration and preserves sciatic nerve function after trauma.

    PubMed

    da Costa, Rodrigo F Madeiro; Martinez, Ana M Blanco; Ferreira, Sergio T

    2010-05-01

    Preventing the harm caused by nerve degeneration is a major challenge in neurodegenerative diseases and in various forms of trauma to the nervous system. The aim of the current work was to investigate the effects of systemic administration of 2,4-dinitrophenol (DNP), a compound with newly recognized neuroprotective properties, on sciatic-nerve degeneration following a crush injury. Sciatic-nerve injury was induced by unilateral application of an aneurysm clip. Four groups of mice were used: uninjured, injured treated with vehicle (PBS), injured treated with two intraperitoneal doses of DNP (0.06 mg DNP/kg every 24 h), and injured treated with four doses of DNP (every 12 h). Animals were sacrificed 48 h post injury and both injured and uninjured (contralateral) sciatic nerves were processed for light and electron microscopy. Morphometric, ultrastructural, and immunohistochemical analysis of injured nerves established that DNP prevented axonal degeneration, blocked cytoskeletal disintegration, and preserved the immunoreactivity of amyloid precursor protein (APP) and Neuregulin 1 (Nrg1), proteins implicated in neuronal survival and myelination. Functional tests revealed preservation of limb function following injury in DNP-treated animals. Results indicate that DNP prevents nerve degeneration and suggest that it may be a useful small-molecule adjuvant in the development of novel therapeutic approaches in nerve injury.

  10. Synergistic effects of micropatterned biodegradable conduits and Schwann cells on sciatic nerve regeneration

    NASA Astrophysics Data System (ADS)

    Rutkowski, Gregory E.; Miller, Cheryl A.; Jeftinija, Srdija; Mallapragada, Surya K.

    2004-09-01

    This paper describes a novel biodegradable conduit that provides a combination of physical, chemical and biological cues at the cellular level to facilitate peripheral nerve regeneration. The conduit consists of a porous poly(D,L-lactic acid) (PDLLA) tubular support structure with a micropatterned inner lumen. Schwann cells were pre-seeded into the lumen to provide additional trophic support. Conduits with micropatterned inner lumens pre-seeded with Schwann cells (MS) were fabricated and compared with three types of conduits used as controls: M (conduits with micropatterned inner lumens without pre-seeded Schwann cells), NS (conduits without micropatterned inner lumens pre-seeded with Schwann cells) and N (conduits without micropatterned inner lumens, without pre-seeded Schwann cells). The conduits were implanted in rats with 1 cm sciatic nerve transections and the regeneration and functional recovery were compared in the four different cases. The number or size of regenerated axons did not vary significantly among the different conduits. The time of recovery, and the sciatic function index, however, were significantly enhanced using the MS conduits, based on qualitative observations as well as quantitative measurements using walking track analysis. This demonstrates that biodegradable micropatterned conduits pre-seeded with Schwann cells that provide a combination of physical, chemical and biological guidance cues for regenerating axons at the cellular level offer a better alternative for repairing sciatic nerve transactions than conventional biodegradable conduits.

  11. Effect of MSH/ACTH peptides on fast axonal transport in intact and regenerating sciatic nerves

    SciTech Connect

    Crescitelli, L.A.

    1985-01-01

    Fast axonal transport was examined in intact rats treated with ACTH 4-10 or ACTH 4-9 (ORG 2766), hypophysectomized rats, adrenalectomized rats, and in ACTH 4-10 treated rats with crushed regenerating sciatic nerves by injecting /sup 3/H-leucine into the ventral horn region of the spinal cord. The distance traveled by the transported activity along the sciatic nerve and the rate of fast axonal transport were not significantly altered as a result of treatment with ACTH 4-10, ACTH 4-9 (ORG 2766), hypophysectomy, or adrenalectomy. Treatment with ACTH 4-9 (ORG 2766) at concentrations of 1 ..mu..g/Kg /day and 10 ..mu..g/Kg/day caused significant reductions (62% and 64% respectively) in the crest height of the fast axonal transport curve as compared to 0.9% saline treated control animals. No significant differences were found in comparing the distance, rate, slope, or crest height of ACTH 4-10 treated animals with crushed regenerating (7 or 14d) sciatic nerves to control animals. In the group of animals in days, the amount of radiolabeled activity was significantly increased in the ACTH 4-10 treated animals as compared to control animals. The results indicate that during regeneration the peptide acts to prolong the initially high levels of synthetic activity which occur in regenerating axons.

  12. Human distal sciatic nerve fascicular anatomy: implications for ankle control using nerve-cuff electrodes.

    PubMed

    Gustafson, Kenneth J; Grinberg, Yanina; Joseph, Sheeba; Triolo, Ronald J

    2012-01-01

    The design of neural prostheses to restore standing balance, prevent foot drop, or provide active propulsion during ambulation requires detailed knowledge of the distal sciatic nerve anatomy. Three complete sciatic nerves and branches were dissected from the piriformis to each muscle entry point to characterize the branching patterns and diameters. Fascicle maps were created from serial sections of each distal terminus below the knee through the anastomosis of the tibial and common fibular nerves above the knee. Similar branching patterns and fascicle maps were observed across specimens. Fascicles innervating primary plantar flexors, dorsiflexors, invertors, and evertors were distinctly separate and functionally organized in the proximal tibial, common fibular, and distal sciatic nerves; however, fascicles from individual muscles were not apparent at these levels. The fascicular organization is conducive to selective stimulation for isolated and/or balanced dorsiflexion, plantar flexion, eversion, and inversion through a single multicontact nerve-cuff electrode. These neuroanatomical data are being used to design nerve-cuff electrodes for selective control of ankle movement and improve current lower-limb neural prostheses.

  13. Effect of Frankincense Extract on Nerve Recovery in the Rat Sciatic Nerve Damage Model

    PubMed Central

    Jiang, Xiaowen; Ma, Jun; Wei, Qingwei; Feng, Xinxin; Qiao, Lu; Liu, Lin; Zhang, Binqing; Yu, Wenhui

    2016-01-01

    This study investigated the effect of frankincense extract on peripheral nerve regeneration in a crush injury rat model. Forty-eight Sprague-Dawley rats were randomly divided into four groups: control and frankincense extract low-, medium-, and high-dose groups. At days 7, 14, 21, and 28 following the surgery, nerve regeneration and functional recovery were evaluated using the sciatic functional index (SFI), expression of GAP-43, and the proliferation of Schwann cells (SCs) in vivo and in vitro. At day 7, the SFI in the frankincense extract high-dose group was significantly improved compared with the control group. After day 14, SFI was significantly improved in the medium- and high-dose groups. There was no significant difference in GAP-43 expression among the groups at day 7. However, after day 14, expression of GAP-43 in the high-dose group was higher than that in the control group. Histological evaluation showed that the injured nerve of frankincense extract high-dose group recovered better than the other groups 28 days after surgery. Further, S100 immunohistochemical staining, MTT colorimetry, and flow cytometry assays all showed that frankincense extract could promote the proliferation of SCs. In conclusion, frankincense extract is able to promote sciatic nerve regeneration and improve the function of a crushed sciatic nerve. This study provides a new direction for the repair of peripheral nerve injury. PMID:27143985

  14. Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension induced disuse

    NASA Technical Reports Server (NTRS)

    Gupta, R. C.; Misulis, K. E.; Dettbarn, W. D.

    1984-01-01

    Muscle disused induced changes in the cholinergic system of sciatic nerve, slow twitch soleus (SOL) and fast twitch extensor digitorum longus (EDL) muscle were studied in rats. Rats with hindlimbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase (ChAT) in sciatic nerve (38%), in SOL (108%) and in EDL (67%). Acetylcholinesterase (AChE) activity in SOL increased by 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant changes in activity and molecular forms pattern of AChE were seen in EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of 3H-acetylcholine was increased in both muscles. When measured after 3 weeks of hindlimb suspension the normal distribution of type 1 fibers in SOL was reduced and a corresponding increase in type IIa and IIb fibers is seen. In EDL no significant change in fiber proportion is observed. Muscle activity, such as loadbearing, appears to have a greater controlling influence on the characteristics of the slow twitch SOL muscle than upon the fast twitch EDL muscle.

  15. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

    PubMed Central

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-01-01

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  16. Carbon-nanotube-interfaced glass fiber scaffold for regeneration of transected sciatic nerve.

    PubMed

    Ahn, Hong-Sun; Hwang, Ji-Young; Kim, Min Soo; Lee, Ja-Yeon; Kim, Jong-Wan; Kim, Hyun-Soo; Shin, Ueon Sang; Knowles, Jonathan C; Kim, Hae-Won; Hyun, Jung Keun

    2015-02-01

    Carbon nanotubes (CNTs), with their unique and unprecedented properties, have become very popular for the repair of tissues, particularly for those requiring electrical stimuli. Whilst most reports have demonstrated in vitro neural cell responses of the CNTs, few studies have been performed on the in vivo efficacy of CNT-interfaced biomaterials in the repair and regeneration of neural tissues. Thus, we report here for the first time the in vivo functions of CNT-interfaced nerve conduits in the regeneration of transected rat sciatic nerve. Aminated CNTs were chemically tethered onto the surface of aligned phosphate glass microfibers (PGFs) and CNT-interfaced PGFs (CNT-PGFs) were successfully placed into three-dimensional poly(L/D-lactic acid) (PLDLA) tubes. An in vitro study confirmed that neurites of dorsal root ganglion outgrew actively along the aligned CNT-PGFs and that the CNT interfacing significantly increased the maximal neurite length. Sixteen weeks after implantation of a CNT-PGF nerve conduit into the 10 mm gap of a transected rat sciatic nerve, the number of regenerating axons crossing the scaffold, the cross-sectional area of the re-innervated muscles and the electrophysiological findings were all significantly improved by the interfacing with CNTs. This first in vivo effect of using a CNT-interfaced scaffold in the regeneration process of a transected rat sciatic nerve strongly supports the potential use of CNT-interfaced PGFs at the interface between the nerve conduit and peripheral neural tissues.

  17. Regeneration-associated genes decline in chronically injured rat sciatic motoneurons.

    PubMed

    Gordon, Tessa; Tetzlaff, Wolfram

    2015-11-01

    Chronic nerve injuries are notorious for their poor regenerative outcomes. Here, we addressed the question of whether the established reduced ability of injured motoneurons to regenerate their axons with time of disconnection with targets (chronic axotomy) is associated with a failure of injured motoneurons to express and sustain their expression of regeneration-associated genes. Sciatic motoneurons were prevented from regenerating by ligation of the transected nerves (chronic axotomy), and then subjected to a second nerve transection (acute axotomy) to mimic the clinical surgical procedure of refreshing the proximal nerve stump prior to delayed nerve repair. The expression of α1-tubulin, actin and GAP-43 mRNA was analysed in axotomized sciatic motoneurons by the use of in situ hybridization followed by autoradiography and silver grain quantification. The expression of these regeneration-associated genes by naive (acutely) axotomized motoneurons declined exponentially, to reach baseline levels within 6 months. These chronically injured motoneurons responded to a refreshment axotomy by elevating the expression of the genes to the same levels as in acutely (i.e. for the first time) axotomized sciatic motoneurons. However, the expression of these declined more rapidly than after acute axotomy. We conclude that a progressive decline in the expression of the regeneration-associated genes in chronically axotomized motoneurons and the even more rapid decline in their expression in response to a refreshment axotomy may explain why the regenerative capacity of chronically axotomized neurons declines with time.

  18. Electrophysiological, behavioral and histological characterization of paclitaxel, cisplatin, vincristine and bortezomib-induced neuropathy in C57Bl/6 mice

    PubMed Central

    Boehmerle, Wolfgang; Huehnchen, Petra; Peruzzaro, Sarah; Balkaya, Mustafa; Endres, Matthias

    2014-01-01

    Polyneuropathy is a frequent and potentially severe side effect of clinical tumor chemotherapy. The goal of this study was to characterize paclitaxel-, cisplatin-, vincristine- and bortezomib-induced neuropathy in C57BL/6 mice with a comparative approach. The phenotype of the animals was evaluated at four time points with behavioral and electrophysiological tests, followed by histology. Treatment protocols used in this study were well tolerated and induced a sensory and predominantly axonal polyneuropathy. Behavioral testing revealed normal motor coordination, whereas all mice receiving verum treatment developed mechanical allodynia and distinct gait alterations. Electrophysiological evaluation showed a significant decrease of the caudal sensory nerve action potential amplitude for all cytostatic agents and a moderate reduction of nerve conduction velocity for cisplatin and paclitaxel. This finding was confirmed by histological analysis of the sciatic nerve which showed predominantly axonal damage: Paclitaxel and vincristine affected mostly large myelinated fibers, bortezomib small myelinated fibers and cisplatin damaged all types of myelinated fibers to a similar degree. Neuropathic symptoms developed faster in paclitaxel and vincristine treated animals compared to cisplatin and bortezomib treatment. The animal models in this study can be used to elucidate pathomechanisms underlying chemotherapy-induced polyneuropathy and for the development of novel therapeutic and preventative strategies. PMID:25231679

  19. 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.

  20. 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.

  1. Diagnosis and classification of autoimmune optic neuropathy.

    PubMed

    Petzold, Axel; Plant, Gordon T

    2014-01-01

    The spectrum of autoimmune optic neuropathies (ON) is extending. The phenotypic spectrum includes single isolated optic neuritis (SION), relapsing isolated optic neuritis (RION), chronic relapsing inflammatory optic neuropathy (CRION), the neuromyelitis optica (NMO) spectrum disorder, multiple sclerosis associated optic neuritis (MSON) and unclassified optic neuritis (UCON) forms. Epidemiological data suggests a slight female predominance. The ethnic heritage is relevant as Caucasian patients are more likely to suffer from MSON, whilst SION, RION, CRION and NMO are more frequent in non-Caucasian patients. Importantly, prognosis for recovery of visual function is good in MSON, but poorer in NMO and CRION which also have a high chance for recurrent episodes. Testing for serum anti-AQP4 autoantibodies is advised in all patients with severe, atypical or recurrent ON because of the high diagnostic specificity. The diagnostic specificity may be aided by testing for glial biomarkers in the CSF and prognostic accuracy by testing for biomarkers for neuroaxonal degeneration. Optical coherence tomography is a highly accurate tool to document the final outcome. The current clinical classification criteria rely on the phenotype, response to treatment and presence of anti-AQP4 autoantibodies.

  2. Mechanisms of diabetic neuropathy: Schwann cells.

    PubMed

    Mizisin, Andrew P

    2014-01-01

    As ensheathing and secretory cells, Schwann cells are a ubiquitous and vital component of the endoneurial microenvironment of peripheral nerves. The interdependence of axons and their ensheathing Schwann cells predisposes each to the impact of injury in the other. Further, the dependence of the blood-nerve interface on trophic support from Schwann cells during development, adulthood, and after injury suggests these glial cells promote the structural and functional integrity of nerve trunks. Here, the developmental origin, injury-induced changes, and mature myelinating and nonmyelinating phenotypes of Schwann cells are reviewed prior to a description of nerve fiber pathology and consideration of pathogenic mechanisms in human and experimental diabetic neuropathy. A fundamental role for aldose-reductase-containing Schwann cells in the pathogenesis of diabetic neuropathy, as well as the interrelationship of pathogenic mechanisms, is indicated by the sensitivity of hyperglycemia-induced biochemical alterations, such as polyol pathway flux, formation of reactive oxygen species, generation of advanced glycosylation end products (AGEs) and deficient neurotrophic support, to blocking polyol pathway flux.

  3. [Antalgic radiotherapy in lumbosacral carcinomatous neuropathies].

    PubMed

    Russi, E G; Gaeta, M; Pergolizzi, S; Settineri, N; Frosina, P; De Renzis, C

    1994-06-01

    Lumbosacral carcinomatous neuropathy (LCN) may be caused by infiltration or compression of the lumbosacral plexi and nerves from intrapelvic or paraaortic neoplasms. The authors submitted 23 patients complaining of LCN with CT documented intrapelvic or paraaortic tumors to palliative radiotherapy. Megavoltage external beam irradiation was administered using a 6-MV linear accelerator. Treatment field sizes ranged from 56 cm2 to 235 cm2 (mean: 150.54 cm2) and encompassed only the site where the disease involved the lumbosacral plexus or its branches. > or = 3 Gy/day fractions were used. Twenty-one of 22 assessable patients (95.4%) obtained LCN pain relief; 19 (86.3%) obtained complete LCN pain relief. The median time to pain progression (TPP) was 150 days (range: 39-510 days). The median survival was 165 days. Seven patients were LCN pain-free at death. Two patients are alive and LCN pain-free. The remaining 12 patients had recurrent LCN pain: four of them were reirradiated at the site of previous neuropathy and only two had partial relief again. The authors conclude that it is advisable to submit to palliative radiotherapy the inoperable disseminated and/or recurrent cancer patients complaining of LCN, to use large fractions not to occupy the extant time of their already short life-expectancy, and to design small fields to avoid acute side-effects.

  4. Early diabetic neuropathy: Triggers and mechanisms

    PubMed Central

    Dobretsov, Maxim; Romanovsky, Dmitry; Stimers, Joseph R

    2007-01-01

    Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major reason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also clear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on clinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia. PMID:17226897

  5. Leber hereditary optic neuropathy: current perspectives

    PubMed Central

    Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. PMID:26170609

  6. Tropical ataxic neuropathy - A century old enigma.

    PubMed

    Netto, Archana B; Netto, Clare M; Mahadevan, Anita; Taly, Arun B; Agadi, J B

    2016-01-01

    Tropical ataxic neuropathy, which is prevalent in the tropics causes significant disability as well as increased mortality and remains an enigmatic disease with no effective treatment or cure, even a century after its identification. The syndrome, first described in Jamaica in 1897 and christened as tropical ataxic neuropathy in 1959, is a constellation of bilateral optic atrophy, bilateral sensory neural deafness, predominant posterior column involvement and pyramidal tract myelopathy, with ataxic polyneuropathy. The exact etiopathogenesis remains unresolved, and several factors have been proposed including malnutrition, vitamin B deficiencies, malabsorption, poor protein consumption, chronic cyanide, and nitrile toxicity, with a strong geospatial endemic prevalence in areas of cassava cultivation. In this review, we summarize the history, epidemiology, clinical features, and controversies regarding the pathogenesis and differential diagnosis of the disease and identify the potential areas for further research concerning this debilitating disorder that is common in the tropics. Its multifactorial etiopathogenesis provides potential opportunities for research and international collaboration to identify novel avenues for treatment.

  7. The Effect of Sildenafil on Recuperation from Sciatic Nerve Injury in Rats

    PubMed Central

    Korkmaz, Mehmet Fatih; Parlakpınar, Hakan; Ceylan, Mehmet Fethi; Ediz, Levent; Şamdancı, Emine; Kekilli, Ersoy; Sağır, Mustafa

    2016-01-01

    Background: Severe functional and anatomical defects can be detected after the peripheral nerve injury. Pharmacological approaches are preferred rather than surgical treatment in the treatment of nerve injuries. Aims: The aim of this study is to perform histopathological, functional and bone densitometry examinations of the effects of sildenafil on nerve regeneration in a rat model of peripheral nerve crush injury. Study Design: Animal experiment. Methods: The study included a total of thirty adult Sprague-Dawley rats that were divided into three groups of ten rats each. In all rats, a crush injury was created by clamping the right sciatic nerve for one minute. One day before the procedure, rats in group 1 were started on a 28-day treatment consisting of a daily dose of 20 mg/kg body weight sildenafil citrate given orally via a nasogastric tube, while the rats in group 2 were started on an every-other-day dose of 10 mg/kg body weight sildenafil citrate. Rats from group 3 were not administered any drugs. Forty-two days after the nerve damage was created, functional and histopathological examination of both sciatic nerves and bone densitometric evaluation of the extremities were conducted. Results: During the rotarod test, rats from group 3 spent the least amount of time on the rod compared to the drug treatment groups at speeds of 20 rpm, 30 rpm and 40 rpm. In addition, the duration for which each animal could stay on the rod throughout the accelerod test significantly reduced in rats from group 3 compared to rats from groups 1 and 2 in the 4-min test. For the hot-plate latency time, there were no differences among the groups in either the basal level or after sciatic nerve injury. Moreover, there was no significant difference between the groups in terms of the static sciatic index (SSI) on the 42nd day (p=0.147). The amplitude was better evaluated in group 1 compared to the other two groups (p<0.05). Under microscopic evaluation, we observed the greatest amount of

  8. The Induction of Heme Oxygenase 1 Decreases Painful Diabetic Neuropathy and Enhances the Antinociceptive Effects of Morphine in Diabetic Mice

    PubMed Central

    Castany, Sílvia; Carcolé, Mireia; Leánez, Sergi; Pol, Olga

    2016-01-01

    Painful diabetic neuropathy is a common complication of diabetes mellitus which is poorly controlled by conventional analgesics. This study investigates if treatment with an heme oxygenase 1 (HO-1) inducer, cobalt protoporphyrin IX (CoPP), could modulate the allodynia and hyperalgesia induced by diabetes and enhanced the antinociceptive effects of morphine. In a diabetic mice model induced by the injection of streptozotocin (STZ), we evaluated the antiallodynic and antihyperalgesic effects produced by the intraperitoneal administration of 5 and 10 mg/kg of CoPP at several days after its administration. The antinociceptive actions produced by the systemic administration of morphine alone or combined with CoPP were also evaluated. In addition, the effects of CoPP treatment on the expression of HO-1, the microglial activation marker (CD11b/c), the inducible nitric oxide synthase (NOS2) and μ-opioid receptors (MOR), were also assessed. Our results showed that the administration of 10 mg/kg of CoPP during 5 consecutive days completely blocked the mechanical and thermal hypersensitivity induced by diabetes. These effects are accompanied by the increased spinal cord, dorsal root ganglia and sciatic nerve protein levels of HO-1. In addition, the STZ-induced activation of microglia and overexpression of NOS2 in the spinal cord were inhibited by CoPP treatment. Furthermore, the antinociceptive effects of morphine were enhanced by CoPP treatment and reversed by the administration of an HO-1 inhibitor, tin protoporphyrin IX (SnPP). The spinal cord expression of MOR was also increased by CoPP treatment in diabetic mice. In conclusion, our data provide the first evidence that the induction of HO-1 attenuated STZ-induced painful diabetic neuropathy and enhanced the antinociceptive effects of morphine via inhibition of microglia activation and NOS2 overexpression as well as by increasing the spinal cord levels of MOR. This study proposes the administration of CoPP alone or

  9. Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.

    PubMed

    Chance, Phillip F

    2006-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often

  10. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects.

    PubMed

    Wang, Yang; Li, Zheng-Wei; Luo, Min; Li, Ya-Jun; Zhang, Ke-Qiang

    2015-06-01

    The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was

  11. Peripheral Neuropathy in Prediabetes and the Metabolic Syndrome.

    PubMed

    Stino, Amro M; Smith, A Gordon

    2017-03-07

    Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with diabetes develop neuropathy, and diabetic neuropathy (DPN) is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall related injury, and foot ulceration and amputation. Most patients with nondiabetic neuropathy have cryptogenic sensory peripheral neuropathy (CSPN). A growing body of literature links prediabetes, obesity and metabolic syndrome (MetS) to risk of both DPN and CSPN (CSPN-MetS). This association may be particularly strong in type 2 diabetes (T2D). There are no effective medical treatments for CSPN or DPN and aggressive glycemic control is an effective approach to neuropathy risk reduction only in type 1 diabetes (T1D). Several studies suggest lifestyle based treatments that integrate dietary counseling with exercise may be a promising therapeutic approach to early DPN in T2D and CSPN-MetS . This article is protected by copyright. All rights reserved.

  12. Motor Nerve Conduction Velocity In Postmenopausal Women with Peripheral Neuropathy

    PubMed Central

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

    2016-01-01

    Introduction The post-menopausal phase is characterized by a decline in the serum oestrogen and progesterone levels. This phase is also associated with higher incidence of peripheral neuropathy. Aim To explore the relationship between the peripheral motor nerve status and serum oestrogen and progesterone levels through assessment of Motor Nerve Conduction Velocity (MNCV) in post-menopausal women with peripheral neuropathy. Materials and Methods This cross-sectional study was conducted at Jawaharlal Nehru Medical College during 2011-2013. The study included 30 post-menopausal women with peripheral neuropathy (age: 51.4±7.9) and 30 post-menopausal women without peripheral neuropathy (control) (age: 52.5±4.9). They were compared for MNCV in median, ulnar and common peroneal nerves and serum levels of oestrogen and progesterone estimated through enzyme immunoassays. To study the relationship between hormone levels and MNCV, a stepwise linear regression analysis was done. Results The post-menopausal women with peripheral neuropathy had significantly lower MNCV and serum oestrogen and progesterone levels as compared to control subjects. Stepwise linear regression analysis showed oestrogen with main effect on MNCV. Conclusion The findings of the present study suggest that while the post-menopausal age group is at a greater risk of peripheral neuropathy, it is the decline in the serum estrogen levels which is critical in the development of peripheral neuropathy. PMID:28208850

  13. Potential Therapeutic Benefits of Maintaining Mitochondrial Health in Peripheral Neuropathies

    PubMed Central

    Areti, Aparna; Yerra, Veera Ganesh; Komirishetty, Prashanth; Kumar, Ashutosh

    2016-01-01

    Background: Peripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy. Method: The current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of maintaining a healthy mitochondrial environment in neuronal cells via pharmacological management in context of peripheral neuropathies. Results: Aberrant cellular signaling coupled with changes in neurotransmission, peripheral and central sensitization are found to be responsible for the pathogenesis of variant toxic neuropathies. Current research reports have indicated the possible involvement of mitochondria mediated redox imbalance as one of the principal causes of neuropathy aetiologies. In addition to imbalance in redox homeostasis, mitochondrial dysfunction is also responsible for alterations in physiological bioenergetic metabolism, apoptosis and autophagy pathways. Conclusions: In spite of various etiological factors, mitochondrial dysfunction has been found to be a major pathomechanism underlying the neuronal dysfunction associated with peripheral neuropathies. Pharmacological modulation of mitochondria either directly or indirectly is expected to yield therapeutic relief from various primary and secondary mitochondrial diseases. PMID:26818748

  14. 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.

  15. 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.

  16. Under-recognised paradox of neuropathy from rapid glycaemic control

    PubMed Central

    Leow, M; Wyckoff, J

    2005-01-01

    Insulin induced neuropathy has been reported previously in people with diabetes treated with insulin, and subsequently reported in patients with insulinomas. However, neuropathy caused by rapid glycaemic control in patients with poorly controlled diabetes with chronic hyperglycaemia is not a widely recognised entity among clinicians worldwide. It is expected that this phenomenon of paradoxical complication of neuropathy in the face of drastic decreases in glycosylated haemoglobin concentrations will assume greater importance with clinicians achieving glycaemic targets at a faster pace than before. PMID:15701742

  17. Neuropathy of nitroimidazole radiosensitizers: clinical and pathological description

    SciTech Connect

    Wasserman, T.H.; Nelson, J.S.; VonGerichten, D.

    1984-09-01

    The dose limiting toxicity of the nitroimidazole radiosensitizers is peripherial neuropathy. Improved pharmacology of newer drugs has eliminated the encephalopathy. Peripheral neuropathies are predominently mild to moderate paresthesias of both hands and feet. Subjective changes occur with or without minimal objective changes on neurologic exam. All of the neuropathies occurred within 30 days of the last drug dose and are of varible duration. Sural nerve biopsies from patients indicate progressive axonal degeneration affecting both large and small caliber myelinated fibers. Axonal damage appears to be more severe in the distal portion of the nerves. More data are needed for correlation of clinical and pathological changes.

  18. Retinal Failure in Diabetes: a Feature of Retinal Sensory Neuropathy.

    PubMed

    Gray, Ellyn J; Gardner, Thomas W

    2015-12-01

    Physiologic adaptations mediate normal responses to short-term and long-term stresses to ensure organ function. Organ failure results if adaptive responses fail to resolve persistent stresses or maladaptive reactions develop. The retinal neurovascular unit likewise undergoes adaptive responses to diabetes resulting in a retinal sensory neuropathy analogous to other sensory neuropathies. Vision-threatening diabetic retinal neuropathy results from unremitting metabolic and inflammatory stresses, leading to macular edema and proliferative diabetic retinopathy, states of "retinal failure." Current regulatory strategies focus primarily on the retinal failure stages, but new diagnostic modalities and understanding of the pathophysiology of diabetic retinopathy may facilitate earlier treatment to maintain vision in persons with diabetes.

  19. Chemotherapy-induced peripheral neuropathy: Current status and progress.

    PubMed

    Brewer, Jamie R; Morrison, Gladys; Dolan, M Eileen; Fleming, Gini F

    2016-01-01

    As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, with a focus on CIPN related to platinum and taxane agents. We will then discuss current clinical models of peripheral neuropathy and ongoing research to better understand CIPN and develop potential treatment options.

  20. Chemotherapy-Induced Peripheral Neuropathy: Current Status and Progress

    PubMed Central

    Brewer, Jamie R; Morrison, Gladys; Dolan, M. Eileen; Fleming, Gini F

    2015-01-01

    As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, with a focus on CIPN related to platinum and taxane agents. We will then discuss current clinical models of peripheral neuropathy and ongoing research to better understand CIPN and develop potential treatment options. PMID:26556766

  1. Contribution of mitochondria to pain in diabetic neuropathy.

    PubMed

    Hernández-Beltrán, Natalia; Moreno, Carlos B; Gutiérrez-Álvarez, Angela María

    2013-01-01

    Diabetes is a metabolic disease affecting approximately 300 million people worldwide. Neuropathy is one of its frequent complications, and may affect sensory, motor, and autonomic nerves. Its pathophysiology has not fully been elucidated. Several hypotheses have been proposed, and mitochondria have been suggested to play a significant role. This article reviews the mechanisms involved in mitochondrial dysfunction and development of diabetic neuropathy, consisting mainly of oxidative and inflammatory stress, changes in intracellular calcium regulation, apoptotic processes, and changes in mitochondrial structure and function that may lead to development of diabetic neuropathy.

  2. Late Onset Neuropathy with Spontaneous Clinical Remission in Mice Lacking the POZ Domain of the Transcription Factor Myc-interacting Zinc Finger Protein 1 (Miz1) in Schwann Cells*

    PubMed Central

    Sanz-Moreno, Adrián; Fuhrmann, David; Zankel, Armin; Reingruber, Herbert; Kern, Lara; Meijer, Dies; Niemann, Axel; Elsässer, Hans-Peter

    2015-01-01

    The transcription factor Miz1 (Myc-interacting zinc finger 1) is a known regulator of the cell cycle but also has cell cycle-independent functions. Here we analyzed the role of Miz1 in the peripheral nervous system, using an early embryonic conditional knock-out model in which the Miz1 POZ domain is ablated in Schwann cells. Although the development of myelinated nerve fibers was not impaired, Miz1ΔPOZ mice acquired behavioral signs of a peripheral neuropathy at the age of 3 months. At this time, ultrastructural analysis of the sciatic nerve showed de- and dysmyelination of fibers, with massive outfoldings and a focal infiltration of macrophages. Although the expression of genes encoding structural myelin proteins, such as periaxin, myelin basic protein, and myelin protein zero, was decreased, genes associated with a negative regulation of myelination, including c-Jun, Sox2, and Id2, were up-regulated in Miz1ΔPOZ mice compared with controls. In animals older than 4 months, the motor disabilities vanished, and the ultrastructure of the sciatic nerve exhibited numerous tomacula and remyelinated fibers, as indicated by thinner myelin. No second acute attack was observed up to the age of 1 year. Thus, the deletion of the Miz1 POZ domain in Schwann cells induces an acute neuropathy with a subsequent regeneration in which there is ongoing balancing between de- and remyelination. Miz1ΔPOZ mice are impaired in the maintenance of myelinated fibers and are a promising model for studying remyelination in adult peripheral nerves. PMID:25416780

  3. Effects of luteolin and luteolin-morphine co-administration on acute and chronic pain and sciatic nerve ligated-induced neuropathy in mice.

    PubMed

    Hashemzaei, Mahmoud; Abdollahzadeh, Mina; Iranshahi, Mehrdad; Golmakani, Ebrahim; Rezaee, Ramin; Tabrizian, Kaveh

    2017-03-01

    Background Neuropathic pain (NP) is a common condition accompanied by nerve injury. To date, there is no definite treatment approved for this disorder. In addition, many drugs that are used for NP cause adverse reactions. Luteolin is a naturally occurring flavonoid with diverse pharmacological properties such as anti-inflammatory, antioxidant and anticancer. We sought to investigate luteolin effects on chronic, acute and neuropathic pain as well as its potential to increase morphine anti-nociceptive effects in mice. Methods Albino mice (20-25 g) were randomly divided into 14 groups (n=7) including morphine 1 mg/kg body weight +luteolin (5 mg/kg body weight), morphine (9 mg/kg body weight, i.p.), luteolin (2.5, 5 and 10 mg/kg body weight), imipramine 40 mg/kg body weight and normal saline (NS) (0.9 %) as vehicle and subjected to hot plate test. Formalin test was done in the following groups: NS, diclofenac sodium (10 mg/kg body weight, i.p.), morphine (9 mg/kg body weight, i.p.) and luteolin (2.5, 5 and 10 mg/kg body weight). Results Administration of luteolin single dose (5 and 10 mg/kg body weight) significantly reduced neuropathic pain ( p<0.05$\\rm{p}<0.05$) in comparison to negative control. Anti-nociceptive effects of luteolin were comparable to imipramine as the standard positive control ( p<0.001$\\rm{p}<0.001$). Co-administration of luteolin and morphine potentiated morphine 1 mg/kg body weight painkilling effects ( p<0.001$\\rm{p}<0.001$). Conclusions Our results showed that luteolin alone reduces neuropathic pain. Furthermore, when co-administered with morphine 1 mg/kg body weight, luteolin potentiates morphine effects. Therefore, luteolin-morphine co-administration might be a valuable alternative for the conventional treatment.

  4. Pyridoxine-induced neuropathy in rats: a sensory neuropathy that responds to 4-methylcatechol.

    PubMed

    Callizot, N; Warter, J M; Poindron, P

    2001-08-01

    Sensory neuropathies are frequently associated with diabetes or with antimitotic treatments in humans suffering from cancer, and are in this case the most important limitation to the use of antimitotic drugs. For this reason, there is a need to establish and validate animal models of sensory neuropathies that could be routinely used, together with the already known models, for studying and evaluating the effects of putative neuroprotective compounds. In the present study, we prove by behavioral and electromyographical analyses that (a) it is possible to induce a nonlethal, exclusively sensory, reversible neuropathy by intoxicating rats with large amounts of pyridoxine, using a new schedule of intoxication; (b) 4-methylcatechol, a drug known to induce nerve growth factor synthesis, improves the clinical status of pyridoxine-intoxicated animals, shortens the duration of the disease, and restores the morphological integrity of the sensory fibers. Owing to its mode of installation and its clinical features, we propose that this model be used as an additional model for preclinical studies of neuroprotective drugs.

  5. Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats.

    PubMed

    Thiagarajan, Venkata R K; Shanmugam, Palanichamy; Krishnan, Uma M; Muthuraman, Arunachalam

    2014-09-01

    The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

  6. Blockade of transient receptor potential cation channel subfamily V member 1 promotes regeneration after sciatic nerve injury

    PubMed Central

    Ren, Fei; Zhang, Hong; Qi, Chao; Gao, Mei-ling; Wang, Hong; Li, Xia-qing

    2015-01-01

    The transient receptor potential cation channel subfamily V member 1 (TRPV1) provides the sensation of pain (nociception). However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517 (300 mg/kg), a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve. PMID:26487864

  7. Chikungunya fever presenting with acute optic neuropathy.

    PubMed

    Mohite, Abhijit Anand; Agius-Fernandez, Adriana

    2015-07-28

    Chikungunya fever is a vector borne virus that typically causes a self-limiting systemic illness with fever, skin rash and joint aches 2 weeks after infection. We present the case of a 69-year-old woman presenting with an acute unilateral optic neuropathy as a delayed complication of Chikungunya virus (CHIKV) infection contracted during a recent trip to the West Indies. She presented to our ophthalmology department with acute painless visual field loss in the right eye and a recent flu-like illness. She was found to have a right relative afferent pupillary defect (RAPD) with unilateral optic disc swelling. Serology confirmed recent CHIKV infection. Treatment with intravenous methylprednisolone was delayed while awaiting MRI scans and serology results. At 5-month follow-up, there was a persistent right RAPD and marked optic atrophy with a corresponding inferior scotoma in the visual field.

  8. Vasculitic neuropathy following exposure to minocycline

    PubMed Central

    Baratta, John M.; Dyck, P. James B.; Brand, Patricio; Thaisetthawatkul, Pariwat; Dyck, Peter J.; Engelstad, JaNean K.; Goodman, Brent

    2015-01-01

    Objective: To report 3 patients with minocycline-induced autoimmunity resulting in peripheral nerve vasculitis. Methods: We report 3 patients who, during minocycline treatment for acne vulgaris, developed subacute onset of pain and weakness caused by vasculitis in single and multiple mononeuropathy patterns. Results: Each patient underwent either a nerve or muscle biopsy that confirmed vasculitis. One patient additionally developed systemic symptoms (including fever, fatigue, and night sweats) and another had a posterior circulation stroke. Symptoms developed with either early or prolonged use of minocycline. Despite withdrawal of minocycline, patients needed long-term immunotherapy to gain neurologic improvement. Conclusions: Our findings suggest that the typical neuropathy associated with minocycline use is painful single or multiple mononeuropathy due to peripheral nerve vasculitis, which may also be accompanied by presumed CNS vasculitis (presenting as stroke). PMID:26601119

  9. Review of Critical Illness Myopathy and Neuropathy

    PubMed Central

    Shepherd, Starane; Batra, Ayush

    2016-01-01

    Critical illness myopathy (CIM) and neuropathy are underdiagnosed conditions within the intensive care setting and contribute to prolonged mechanical ventilation and ventilator wean failure and ultimately lead to significant morbidity and mortality. These conditions are often further subdivided into CIM, critical illness polyneuropathy (CIP), or the combination—critical illness polyneuromyopathy (CIPNM). In this review, we discuss the epidemiology and pathophysiology of CIM, CIP, and CIPNM, along with diagnostic considerations such as detailed clinical examination, electrophysiological studies, and histopathological review of muscle biopsy specimens. We also review current available treatments and prognosis. Increased awareness and early recognition of CIM, CIP, and CIPNM in the intensive care unit setting may lead to earlier treatments and rehabilitation, improving patient outcomes. PMID:28042370

  10. Peripheral neuropathy: pathogenic mechanisms and alternative therapies.

    PubMed

    Head, Kathleen A

    2006-12-01

    Peripheral neuropathy (PN), associated with diabetes, neurotoxic chemotherapy, human immunodeficiency virus (HIV)/antiretroviral drugs, alcoholism, nutrient deficiencies, heavy metal toxicity, and other etiologies, results in significant morbidity. Conventional pain medications primarily mask symptoms and have significant side effects and addiction profiles. However, a widening body of research indicates alternative medicine may offer significant benefit to this patient population. Alpha-lipoic acid, acetyl-L-carnitine, benfotiamine, methylcobalamin, and topical capsaicin are among the most well-researched alternative options for the treatment of PN. Other potential nutrient or botanical therapies include vitamin E, glutathione, folate, pyridoxine, biotin, myo-inositol, omega-3 and -6 fatty acids, L-arginine, L-glutamine, taurine, N-acetylcysteine, zinc, magnesium, chromium, and St. John's wort. In the realm of physical medicine, acupuncture, magnetic therapy, and yoga have been found to provide benefit. New cutting-edge conventional therapies, including dual-action peptides, may also hold promise.

  11. The mitochondrial connection in auditory neuropathy.

    PubMed

    Cacace, Anthony T; Pinheiro, Joaquim M B

    2011-01-01

    'Auditory neuropathy' (AN), the term used to codify a primary degeneration of the auditory nerve, can be linked directly or indirectly to mitochondrial dysfunction. These observations are based on the expression of AN in known mitochondrial-based neurological diseases (Friedreich's ataxia, Mohr-Tranebjærg syndrome), in conditions where defects in axonal transport, protein trafficking, and fusion processes perturb and/or disrupt mitochondrial dynamics (Charcot-Marie-Tooth disease, autosomal dominant optic atrophy), in a common neonatal condition known to be toxic to mitochondria (hyperbilirubinemia), and where respiratory chain deficiencies produce reductions in oxidative phosphorylation that adversely affect peripheral auditory mechanisms. This body of evidence is solidified by data derived from temporal bone and genetic studies, biochemical, molecular biologic, behavioral, electroacoustic, and electrophysiological investigations.

  12. Targeting mitochondrial function to treat optic neuropathy.

    PubMed

    Gueven, Nuri; Nadikudi, Monila; Daniel, Abraham; Chhetri, Jamuna

    2016-07-28

    Many reports have illustrated a tight connection between vision and mitochondrial function. Not only are most mitochondrial diseases associated with some form of vision impairment, many ophthalmological disorders such as glaucoma, age-related macular degeneration and diabetic retinopathy also show signs of mitochondrial dysfunction. Despite a vast amount of evidence, vision loss is still only treated symptomatically, which is only partially a consequence of resistance to acknowledge that mitochondria could be the common denominator and hence a promising therapeutic target. More importantly, clinical support of this concept is only emerging. Moreover, only a few drug candidates and treatment strategies are in development or approved that selectively aim to restore mitochondrial function. This review rationalizes the currently developed therapeutic approaches that target mitochondrial function by discussing their proposed mode(s) of action and provides an overview on their development status with regards to optic neuropathies.

  13. Chaperonopathies: Spotlight on Hereditary Motor Neuropathies

    PubMed Central

    Lupo, Vincenzo; Aguado, Carmen; Knecht, Erwin; Espinós, Carmen

    2016-01-01

    Distal hereditary motor neuropathies (dHMN) are a group of rare hereditary neuromuscular disorders characterized by an atrophy that affects peroneal muscles in the absence of sensory symptoms. To date, 23 genes are thought to be responsible for dHMN, four of which encode chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family; and HSPB1, HSPB3, and HSPB8, encoding three members of the small heat shock protein family. While around 30 different mutations in HSPB1 have been identified, the remaining three genes are altered in many fewer cases. Indeed, a mutation of HSPB3 has only been described in one case, whereas a few cases have been reported carrying mutations in DNAJB2 and HSPB8, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the K141 residue in the HSPB8 chaperone. Hence, their rare occurrence makes it difficult to understand the pathological mechanisms driven by such mutations in this neuropathy. Chaperones can assemble into multi-chaperone complexes that form an integrated chaperone network within the cell. Such complexes fulfill relevant roles in a variety of processes, such as the correct folding of newly synthesized proteins, in which chaperones escort them to precise cellular locations, and as a response to protein misfolding, which includes the degradation of proteins that fail to refold properly. Despite this range of functions, mutations in some of these chaperones lead to diseases with a similar clinical profile, suggesting common pathways. This review provides an overview of the genetics of those dHMNs that share a common disease mechanism and that are caused by mutations in four genes encoding chaperones: DNAJB2, HSPB1, HSPB3, and HSPB8. PMID:28018906

  14. Hereditary sensory radicular neuropathy: defective neurogenic inflammation.

    PubMed

    Westerman, R A; Block, A; Nunn, A; Delaney, C A; Hahn, A; Dennett, X; Carr, R W

    1992-01-01

    Hereditary sensory radicular neuropathy exhibits autosomal dominant inheritance with complete penetrance in males and incomplete penetrance in females. Newer tests of small sensory nerve function were used in screening 8 family members aged between 14 and 66 years. All exhibited some frequent features of the disorder with an onset in the 2nd or 3rd decade, foot ulceration, foot callus, loss of pin prick, thermal and light touch sensation, and some reduction in vibration acuity and proprioception in the lower limbs. The hands were involved in 3 of 8, muscle involvement was present in 5 of 8, but deafness was not detected by audiometry. Nerve conduction velocity, sensory action potentials, latency and amplitude, thermal acuity, vibration acuity and axon reflex flares were measured in all patients. One sural nerve biopsy confirmed the presence of peripheral fibre loss in this predominantly sensory neuropathy. Chemically evoked axon reflex tests were used to evaluate the extent of primary sensory nerve fibre involvement. All patients were tested using a Moor MBF 3-D dual channel laser Doppler velocimeter. Acetylcholine or phenylephrine iontophoretically applied as 16 mC doses evoked absent or tiny axon reflexes in areas of impaired pin prick sensation. By contrast, direct microvascular dilator responses to nitroprusside (smooth muscle dependent) and acetylcholine (endothelium-dependent) were present but somewhat reduced in areas with defective neurogenic inflammation. These results differ significantly from the responses obtained in age-matched healthy controls (P < 0.05). Foot pressure analysis was performed for orthoses in 2 affected members with foot ulceration using the Musgrave Footprint system.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Chaperonopathies: Spotlight on Hereditary Motor Neuropathies.

    PubMed

    Lupo, Vincenzo; Aguado, Carmen; Knecht, Erwin; Espinós, Carmen

    2016-01-01

    Distal hereditary motor neuropathies (dHMN) are a group of rare hereditary neuromuscular disorders characterized by an atrophy that affects peroneal muscles in the absence of sensory symptoms. To date, 23 genes are thought to be responsible for dHMN, four of which encode chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family; and HSPB1, HSPB3, and HSPB8, encoding three members of the small heat shock protein family. While around 30 different mutations in HSPB1 have been identified, the remaining three genes are altered in many fewer cases. Indeed, a mutation of HSPB3 has only been described in one case, whereas a few cases have been reported carrying mutations in DNAJB2 and HSPB8, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the K141 residue in the HSPB8 chaperone. Hence, their rare occurrence makes it difficult to understand the pathological mechanisms driven by such mutations in this neuropathy. Chaperones can assemble into multi-chaperone complexes that form an integrated chaperone network within the cell. Such complexes fulfill relevant roles in a variety of processes, such as the correct folding of newly synthesized proteins, in which chaperones escort them to precise cellular locations, and as a response to protein misfolding, which includes the degradation of proteins that fail to refold properly. Despite this range of functions, mutations in some of these chaperones lead to diseases with a similar clinical profile, suggesting common pathways. This review provides an overview of the genetics of those dHMNs that share a common disease mechanism and that are caused by mutations in four genes encoding chaperones: DNAJB2, HSPB1, HSPB3, and HSPB8.

  16. Biochemical studies of patients with Cuban epidemic neuropathy.

    PubMed

    Rodríguez-Hernandez, M; Hirano, M; Naini, A; Santiestéban, R

    2001-01-01

    In 1992-1994, a disorder known as the epidemic neuropathy afflicted more than 50,000 Cubans. Three different forms of the illness were identified: epidemic optic neuropathy, peripheral neuropathy and mixed optic and peripheral neuropathy. The causes are still unknown. Skeletal muscle biopsy samples were analyzed by standard histological techniques and by biochemical assays. Elevated activities of citrate synthase, a non-respiratory-chain mitochondrial matrix enzyme, suggested possible mitochondrial proliferation in 7 of the 8 patients. Nicotinamide adenine dinucleotide phosphate (NADP(+)) levels were higher in the patients than in the controls (p = 0.04). Levels of nicotinamide adenine dinucleotide (NAD) and the reduced compounds NADH and NADPH were comparable in patients and controls. Elevations of succinate dehydrogenase and citrate synthase activities and high NADP(+) levels suggest that alterations of mitochondrial functions may be associated with this disorder.

  17. Antioxidant Strategies in the Management of Diabetic Neuropathy

    PubMed Central

    Oyenihi, Ayodeji Babatunde; Ayeleso, Ademola Olabode; Masola, Bubuya

    2015-01-01

    Chronic hyperglycaemia (an abnormally high glucose concentration in the blood) resulting from defects in insulin secretion/action, or both, is the major hallmark of diabetes in which it is known to be involved in the progression of the condition to different complications that include diabetic neuropathy. Diabetic neuropathy (diabetes-induced nerve damage) is the most common diabetic complication and can be devastating because it can lead to disability. There is an increasing body of evidence associating diabetic neuropathy with oxidative stress. Oxidative stress results from the production of oxygen free radicals in the body in excess of its ability to eliminate them by antioxidant activity. Antioxidants have different mechanisms and sites of actions by which they exert their biochemical effects and ameliorate nerve dysfunction in diabetes by acting directly against oxidative damage. This review will examine different strategies for managing diabetic neuropathy which rely on exogenous antioxidants. PMID:25821809

  18. Schwann cell interactions with axons and microvessels in diabetic neuropathy.

    PubMed

    Gonçalves, Nádia P; Vægter, Christian B; Andersen, Henning; Østergaard, Leif; Calcutt, Nigel A; Jensen, Troels S

    2017-03-01

    The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annually. The most common complication of diabetes is peripheral neuropathy, which has a prevalence as high as 50% and is characterized by damage to neurons, Schwann cells and blood vessels within the nerve. The pathogenic mechanisms of diabetic neuropathy remain poorly understood, impeding the development of targeted therapies to treat nerve degeneration and its most disruptive consequences of sensory loss and neuropathic pain. Involvement of Schwann cells has long been proposed, and new research techniques are beginning to unravel a complex interplay between these cells, axons and microvessels that is compromised during the development of diabetic neuropathy. In this Review, we discuss the evolving concept of Schwannopathy as an integral factor in the pathogenesis of diabetic neuropathy, and how disruption of the interactions between Schwann cells, axons and microvessels contribute to the disease.

  19. Peripheral neuropathy: evidence-based treatment of a complex disorder.

    PubMed

    Hammersla, Margaret; Kapustin, Jane Faith

    2012-05-11

    Peripheral neuropathy (PN) is a common and often progressive condition frequently seen in primary care. The chronic pain associated with PN, or neuropathic pain, can significantly diminish patients' quality of life and be challenging to treat.

  20. Familial Idiopathic Cranial Neuropathy in a Chinese Family.

    PubMed

    Zhang, Li; Liang, Jianfeng; Yu, Yanbing

    Cranial neuropathy is usually idiopathic and familial cases are uncommon. We describe a family with 5 members with cranial neuropathy over 3 generations. All affected patients were women, indicating an X-linked dominant or an autosomal dominant mode of inheritance. Our cases and a review of the literature suggest that familial idiopathic cranial neuropathy is a rare condition which may be related to autosomal dominant vascular disorders (e.g. vascular tortuosity, sclerosis, elongation or extension), small posterior cranial fossas, anatomical variations of the posterior circulation, hypersensitivity of cranial nerves and other abnormalities. Moreover, microvascular decompression is the treatment of choice because vascular compression is the main factor in the pathogenesis. To the best of our knowledge, this is the first report of familial cranial neuropathy in China.

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

    PubMed

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

    2014-01-01

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

  2. Peripheral neuropathy following intentional inhalation of naphtha fumes.

    PubMed Central

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

    1984-01-01

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

  3. Complications of Compressive Neuropathy: Prevention and Management Strategies

    PubMed Central

    Santosa, Katherine B.; Chung, Kevin C.; Waljee, Jennifer F.

    2016-01-01

    Compressive neuropathies of the upper extremity are common and can result in profound disability if left untreated. Nerve releases are frequently performed, but can be complicated by both iatrogenic events as well as progression of neuropathy. In this review, we will examine the management of post-operative complications following two common nerve compression release procedures: carpal tunnel release and cubital tunnel release. PMID:25934192

  4. Pathogenesis and Treatment of Immune-Mediated Neuropathies

    PubMed Central

    Lehmann, Helmar C.; zu Horste, Gerd Meyer; Kieseier, Bernd C.

    2009-01-01

    Immune-mediated neuropathies represent a heterogeneous spectrum of peripheral nerve disorders that can be classified according to time course, predominant involvement of motor/sensory fibers, distribution of deficits and paraclinical parameters such as electrophysiology and serum antibodies. In the last few years, significant advances have been achieved in elucidating underlying pathomechanisms, which made it possible to identify potential therapeutic targets. In this review, we discuss the latest development in pathogenesis and treatment of immune-mediated neuropathies. PMID:21179533

  5. Orthostatic intolerance in multifocal acquired demyelinating sensory and motor neuropathy.

    PubMed

    Tramontozzi, Louis A; Russell, James A

    2012-09-01

    We report a patient with orthostatic intolerance and syncope as a major clinical manifestation of an acquired multifocal neuropathy with the clinical, electrodiagnostic, and cerebrospinal fluid features of multifocal acquired demyelinating sensory and motor neuropathy or the Lewis-Sumner syndrome. Immunomodulatory therapy led to clinical remission of both somatic and autonomic signs and symptoms. We are unaware of a previous description of symptomatic dysautonomia in this disorder.

  6. Neurotoxicity of perineural vs intraneural-extrafascicular injection of liposomal bupivacaine in the porcine model of sciatic nerve block.

    PubMed

    Damjanovska, M; Cvetko, E; Hadzic, A; Seliskar, A; Plavec, T; Mis, K; Vuckovic Hasanbegovic, I; Stopar Pintaric, T

    2015-12-01

    Liposomal bupivacaine is a prolonged-release local anaesthetic, the neurotoxicity of which has not yet been determined. We used quantitative histomorphometric and immunohistochemical analyses to evaluate the neurotoxic effect of liposomal bupivacaine after perineural and intraneural (extrafascicular) injection of the sciatic nerve in pigs. In this double-blind prospective randomised trial, 4 ml liposomal bupivacaine 1.3% was injected either perineurally (n = 5) or intraneurally extrafascicularly (n = 5). Intraneural-extrafascicular injection of saline (n = 5) was used as a control. After emergence from anaesthesia, neurological examinations were conducted over two weeks. After harvesting the sciatic nerves, no changes in nerve fibre density or myelin width indicative of nerve injury were observed in any of the groups. Intraneural injections resulted in longer sensory blockade than perineural (p < 0.003) without persistent motor or sensory deficit. Sciatic nerve block with liposomal bupivacaine in pigs did not result in histological evidence of nerve injury.

  7. Deep gluteal syndrome: anatomy, imaging, and management of sciatic nerve entrapments in the subgluteal space.

    PubMed

    Hernando, Moisés Fernández; Cerezal, Luis; Pérez-Carro, Luis; Abascal, Faustino; Canga, Ana

    2015-07-01

    Deep gluteal syndrome (DGS) is an underdiagnosed entity characterized by pain and/or dysesthesias in the buttock area, hip or posterior thigh and/or radicular pain due to a non-discogenic sciatic nerve entrapment in the subgluteal space. Multiple pathologies have been incorporated in this all-included "piriformis syndrome," a term that has nothing to do with the presence of fibrous bands, obturator internus/gemellus syndrome, quadratus femoris/ischiofemoral pathology, hamstring conditions, gluteal disorders and orthopedic causes. The concept of fibrous bands playing a role in causing symptoms related to sciatic nerve mobility and entrapment represents a radical change in the current diagnosis of and therapeutic approach to DGS. The development of periarticular hip endoscopy has led to an understanding of the pathophysiological mechanisms underlying piriformis syndrome, which has supported its further classification. A broad spectrum of known pathologies may be located nonspecifically in the subgluteal space and can therefore also trigger DGS. These can be classified as traumatic, iatrogenic, inflammatory/infectious, vascular, gynecologic and tumors/pseudo-tumors. Because of the ever-increasing use of advanced magnetic resonance neurography (MRN) techniques and the excellent outcomes of the new endoscopic treatment, radiologists must be aware of the anatomy and pathologic conditions of this space. MR imaging is the diagnostic procedure of choice for assessing DGS and may substantially influence the management of these patients. The infiltration test not only has a high diagnostic but also a therapeutic value. This article describes the subgluteal space anatomy, reviews known and new etiologies of DGS, and assesses the role of the radiologist in the diagnosis, treatment and postoperative evaluation of sciatic nerve entrapments, with emphasis on MR imaging and endoscopic correlation.

  8. KLF7-transfected Schwann cell graft transplantation promotes sciatic nerve regeneration.

    PubMed

    Wang, Ying; Li, Wen-Yuan; Jia, Hua; Zhai, Feng-Guo; Qu, Wen-Rui; Cheng, Yong-Xia; Liu, Yan-Cui; Deng, Ling-Xiao; Guo, Su-Fen; Jin, Zai-Shun

    2017-01-06

    Our former study demonstrated that Krüppel-like Factor 7 (KLF7) is a transcription factor that stimulates axonal regeneration after peripheral nerve injury. Currently, we used a gene therapy approach to overexpress KLF7 in Schwann cells (SCs) and assessed whether KLF7-transfected SCs graft could promote sciatic nerve regeneration. SCs were transfected by adeno-associated virus 2 (AAV2)-KLF7 in vitro. Mice were allografted by an acellular nerve (ANA) with either an injection of DMEM (ANA group), SCs (ANA+SCs group) or AAV2-KLF7-transfected SCs (ANA+KLF7-SCs group) to assess repair of a sciatic nerve gap. The results indicate that KLF7 overexpression promoted the proliferation of both transfected SCs and native SCs. The neurite length of the dorsal root ganglia (DRG) explants was enhanced. Several beneficial effects were detected in the ANA+KLF7-SCs group including an increase in the compound action potential amplitude, sciatic function index score, enhanced expression of PKH26-labeling transplant SCs, peripheral myelin protein 0, neurofilaments, S-100, and myelinated regeneration nerve. Additionally, HRP-labeled motoneurons in the spinal cord, CTB-labeled sensory neurons in the DRG, motor endplate density and the weight ratios of target muscles were increased by the treatment while thermal hyperalgesia was diminished. Finally, expression of KLF7, NGF, GAP43, TrkA and TrkB were enhanced in the grafted SCs, which may indicate that several signal pathways may be involved in conferring the beneficial effects from KLF7 overexpression. We concluded that KLF7-overexpressing SCs promoted axonal regeneration of the peripheral nerve and enhanced myelination, which collectively proved KLF-SCs as a novel therapeutic strategy for injured nerves.

  9. Effect of Zofenopril on regeneration of sciatic nerve crush injury in a rat model

    PubMed Central

    2009-01-01

    Background Zofenopril is an antioxidant agent which has been shown to have beneficial effects in hypertension and heart failure. The aim of this study was to test the effects of Zofenopril on nerve regeneration and scarring in a rat model of peripheral nerve crush injury. Methods Twenty-one adult Sprague-Dawley rats underwent a surgical procedure involving right sciatic nerve crush injury. 15 mg/kg Zofenopril was administered orally to seven rats in group Z for seven days. Seven rats in group S received saline orally for seven days. Seven rats in the control group C received no drug after crush injury. Fourteenth and 42nd days after injury, functional and electromyography assessments of nerves were performed. Functional recovery was analyzed using a walking track assessment, and quantified using the sciatic functional index (SFI). After these evaluations, all rats were sacrificed and microscopic evaluations were performed. Results The Sciatic functional Index (SFI) in group Z on 14th day is different significantly from group S and group C (p = 0.037). But on 42nd day there was no difference between groups (p = 0.278). The statistical analyses of electromyelographic (EMG) studies showed that the latency in group Z is significantly different from group S (p = 0.006) and group C (p = 0.045). But on 42nd day there was no difference between groups like SFI (p = 0.147). The amplitude was evaluated better in group Z than others (p < 0.05). In microscopic evaluation, we observed the highest number of nerve regeneration in the group Z and the lowest in the group C. But it was not significant statistically. Conclusion Our results demonstrate that Zofenopril promotes the regeneration of peripheral nerve injuries in rat models. PMID:19508704

  10. Influence of age on the late retrograde effects of sciatic nerve section in the rat.

    PubMed Central

    Kerezoudi, E; King, R H; Muddle, J R; O'Neill, J A; Thomas, P K

    1995-01-01

    The influence of age on the late retrograde effects of unilateral sciatic nerve section was investigated in rats. Operations were performed on young rats aged 3 months and older rats aged 15 and 18 months, with survival times ranging from 6 to 15 months depending upon age at the time of operation. As in previous studies, axonal atrophy was found in myelinated fibres proximal to nerve transection. This was observed to be greater in animals operated upon at 3 months of age than in those in which the sciatic nerve was transected at 15 and 18 months. In the sciatic nerve, focal intramyelinic oedema was present at a low frequency on the operated side just proximal to the section at all survival times but not on the unoperated side except in 1 old animal. Its frequency increased with age both in the dorsal and ventral roots on both sides but it was not more common on the operated side. Retrograde axonal atrophy is therefore unlikely to contribute to its occurrence. In the dorsal root ganglia the main abnormality was the presence of vacuolated neurons on the operated side. Nuclear eccentricity was also observed on the operated side in young animals in a proportion of the neurons; its frequency increased with age on the normal side and there was no difference in the older animals between operated and control sides. The possibility is discussed that growth factor deprivation secondary to axotomy is implicated in these changes. If so, there are age differences in its effect in giving rise to axonal atrophy and neuronal vacuolation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7591983

  11. (-)-Epigallocatechin-3-gallate (EGCG) attenuates peripheral nerve degeneration in rat sciatic nerve crush injury.

    PubMed

    Renno, Waleed M; Al-Maghrebi, May; Alshammari, Ahmad; George, Preethi

    2013-02-01

    Recently, we have shown that green tea (GT) consumption improves both reflexes and sensation in unilateral chronic constriction injury to the sciatic nerve. Considering the substantial neuroprotective properties of GT polyphenols, we sought to investigate whether (-)-epigallocatechin-3-gallate (EGCG) could protect the sciatic nerve and improve functional impairments induced by a crushing injury. We also examined whether neuronal cell apoptosis induced by the crushing injury is affected by EGCG treatment. Histological examination of sciatic nerves from EGCG-treated (50mg/kg; i.p.) showed that axonotmized rats had a remarkable axonal and myelin regeneration with significant decrease in the number of myelinated axonal fibers compared to vehicle-treated crush group. Similarly, ultrastructural evaluation of EGCG-treated nerves displayed normal unmyelinated and myelinated axons with regular myelin sheath thickness and normalized appearance of Schmidt-Lantermann clefts. Extracellular matrix displayed normal collagen fibers appearance with distinctively organized distribution similar to sham animals. Analysis of foot position and extensor postural thrust test showed a progressive and faster recovery in the EGCG-treated group compared to vehicle-treated animals. EGCG-treated rats showed significant increase in paw withdrawal thresholds to mechanical stimulation compared to vehicle-treated crush group. EGCG treatment also restored the mRNA expression of Bax, Bcl-2 and survivin but not that of p53 to sham levels on days 3 and 7 post-injury. Our results demonstrate that EGCG treatment enhanced functional recovery, advanced morphological nerve rescue and accelerated nerve regeneration following crush injury partly due to the down regulation of apoptosis related genes.

  12. Reversal of dysthyroid optic neuropathy following orbital fat decompression

    PubMed Central

    Kazim, M.; Trokel, S.; Acaroglu, G.; Elliott, A.

    2000-01-01

    AIMS—To document the successful treatment of five patients with dysthyroid optic neuropathy by orbital fat decompression instead of orbital bone decompression after failed medical therapy.
METHODS—Eight orbits of five patients with dysthyroid optic neuropathy were selected for orbital fat decompression as an alternative to bone removal decompression. Treatment with systemic corticosteroids and/or orbital radiotherapy was either unsuccessful or contraindicated in each case. All patients satisfied clinical indications for orbital bone decompression to reverse the optic neuropathy. High resolution computerised tomographic (CT) scans were performed in all cases and in each case showed signs of enlargement of the orbital fat compartment. As an alternative to bone decompression, orbital fat decompression was performed on all eight orbits.
RESULTS—Orbital fat decompression was performed on five patients (eight orbits) with optic neuropathy. Optic neuropathy was reversed in all cases. There were no cases of postoperative diplopia, enophthalmos, globe ptosis, or anaesthesia. All patients were followed for a minimum of 1 year.
CONCLUSIONS—In a subset of patients with an enlarged orbital fat compartment and in whom extraocular muscle enlargement is not the solitary cause of optic neuropathy, fat decompression is a surgical alternative to bony decompression.

 PMID:10837384

  13. 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

  14. Nrf2: a potential therapeutic target for diabetic neuropathy.

    PubMed

    Kumar, Anil; Mittal, Ruchika

    2017-03-28

    Different aspects involved in pathophysiology of diabetic neuropathy are related to inflammatory and apoptotic pathways. This article summarizes evidence that Nrf2 acts as a bridging link in various inflammatory and apoptotic pathways impacting progression of diabetic neuropathy. Nrf2 is involved in expression of various antioxidant proteins (such as detoxifying enzymes) via antioxidant response element (ARE) binding site. Under normal conditions, Nrf2 is inactive and remains in the cytosol. Hyperglycemia is a strong stimulus for oxidative stress and inflammation that downregulates the activity of Nrf2 through various neuroinflammatory pathways. Acute hyperglycemia increases the expression of Nrf2, but persistent hyperglycemia decreases its expression. This downregulation of Nrf2 causes various microvascular changes, which result in diabetic neuropathy. The key contribution of Nrf2 in progression of diabetic neuropathy has been summarized in the article. Despite involvement of Nrf2 in progression of diabetic neuropathy, targeting Nrf2 activators as a therapeutic potential will provide important new insights into the ways that influence treatment of diabetic neuropathy.

  15. Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy.

    PubMed

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

    2017-02-15

    Impaired rate dependent depression (RDD) of the Hoffman-reflex is associated with reduced dorsal spinal cord potassium chloride co-transporter expression and impaired spinal GABAA receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5HT2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy when compared to healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fibre pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help to identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine.

  16. [High resolution (3 T) magnetic resonance neurography of the sciatic nerve].

    PubMed

    Cejas, C; Aguilar, M; Falcón, L; Caneo, N; Acuña, M C

    2013-01-01

    Magnetic resonance (MR) neurography refers to a set of techniques that enable the structure of the peripheral nerves and nerve plexuses to be evaluated optimally. New two-dimensional and three-dimensional neurographic sequences, in particular in 3T scanners, achieve excellent contrast between the nerve and perineural structures. MR neurography makes it possible to distinguish between the normal fascicular pattern of the nerve and anomalies like inflammation, trauma, and tumor that can affect nerves. In this article, we describe the structure of the sciatic nerve, its characteristics on MR neurography, and the most common diseases that affect it.

  17. Epidermal laser stimulation of action potentials in the frog sciatic nerve

    NASA Astrophysics Data System (ADS)

    Jindra, Nichole M.; Goddard, Douglas; Imholte, Michelle; Thomas, Robert J.

    2010-01-01

    Measurements of laser-stimulated action potentials in the sciatic nerve of leopard frogs (Rana pipiens) are made using two infrared lasers. The dorsal sides of the frog's hind limbs are exposed to short-pulsed 1540- and 1064-nm wavelengths at three separate spot sizes: 2, 3, and 4 mm. Energy density thresholds are determined for eliciting an action potential at each experimental condition. Results from these exposures show similar evoked potential thresholds for both wavelengths. The 2-mm-diam spot sizes yield action potentials at radiant exposure levels almost double that seen with larger beam sizes.

  18. Enhanced rat sciatic nerve regeneration through silicon tubes implanted with valproic acid.

    PubMed

    Wu, Fei; Xing, Danmou; Peng, Zhengren; Rao, Ting

    2008-05-01

    Valproic acid (VPA) is an effective antiepileptic drug and mood stabilizer. It has recently been demonstrated that VPA could promote neurite outgrowth, activate the extracellular signal-regulated kinase pathway, and increase B-cell lymphoma/leukemia-2 (bcl-2)and growth cone-associated protein 43 (GAP-43) levels in spinal cord. We hypothesized that VPA could enhance axonal regeneration in the rat. In the present research, we demonstrate the effect of VPA on peripheral nerve regeneration and recovery of motor function through a silicon tube implanted with VPA. The left sciatic nerves were exposed through dorsal-splitting incisions, and 8-mm nerve sections were excised at the middle of the thigh. Then, a 1.0-cm-long silicone tube (internal diameter,1.0 mm; exterior diameter, 2.0 mm) was used to bridge the nerve deficit, anchored to the proximal and distal terminals of the excised deficit of sciatic nerves with 9-0 nylon epineural suture. Sterile petroleum jelly was used to seal the ends of the tubes to avoid leakage. The rats in the VPA group and control group were locally delivered 10 muL VPA injection (400 mg/5 mL) and normal saline, respectively, after the operation. The sciatic nerve index (SFI) was observed in each animal at 2-week intervals and electrophysiology was studied at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed at the end of the experiment (12 weeks after the operation). Using the digital image-analysis system, the thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity, amplitude of activity potential), and morphometrical results (regenerated axon number and thickness of myelin sheath) in nerve regeneration between the VPA group and controls ( P < 0.05). The results demonstrated that VPA is able to enhance sciatic nerve regeneration in rats, suggesting the potential

  19. Primo-vessels and primo-nodes in rat brain, spine and sciatic nerve.

    PubMed

    Lee, Byung-Cheon; Eom, Ki-Hoon; Soh, Kwang-Sup

    2010-06-01

    We report a method using Trypan blue staining to detect primo-vessels in the nervous system on internal organs or in the skin of rat. We applied this technique to visualize the primo-vessels and primo-nodes in the brain, spinal cord and sciatic nerve of a rat. Primo-vessels and primo-nodes were preferentially stained at nerves, blood vessels, or fascia-like membranes and turned blue after the spread and washing of Trypan blue. The physiological role of the primo-vessels within the nervous system is an important question warranting further investigation.

  20. Regulation of ciliary neurotrophic factor receptor alpha in sciatic motor neurons following axotomy.

    PubMed

    MacLennan, A J; Devlin, B K; Neitzel, K L; McLaurin, D L; Anderson, K J; Lee, N

    1999-01-01

    Spinal motor neurons are one of the few classes of neurons capable of regenerating axons following axotomy. Injury-induced expression of neurotrophic factors and corresponding receptors may play an important role in this rare ability. A wide variety of indirect data suggests that ciliary neurotrophic factor receptor alpha may critically contribute to the regeneration of injured spinal motor neurons. We used immunohistochemistry, in situ hybridization and retrograde tracing techniques to study the regulation of ciliary neurotrophic factor receptor alpha in axotomized sciatic motor neurons. Ciliary neurotrophic factor receptor alpha immunoreactivity, detected with two independent antisera, is increased in a subpopulation of caudal sciatic motor neuron soma one, two and six weeks after sciatic nerve transection and reattachment, while no changes are detected at one day and 15 weeks post-lesion. Ciliary neurotrophic factor receptor alpha messenger RNA levels are augmented in the same classes of neurons following an identical lesion, suggesting that increased synthesis contributes, at least in part, to the additional ciliary neurotrophic factor receptor alpha protein. Separating the proximal and distal nerve stumps with a plastic barrier does not noticeably affect the injury-induced change in ciliary neurotrophic factor receptor alpha regulation, thereby indicating that this injury response is not dependent on signals distal to the lesion traveling retrogradely through the nerve or signals generated by axonal growth through the distal nerve. The prolonged increases in ciliary neurotrophic factor receptor alpha protein and messenger RNA found in regenerating sciatic motor neurons contrast with the responses of non-regenerating central neurons, which are reported to display, at most, a short-lived increase in ciliary neurotrophic factor receptor alpha messenger RNA expression following injury. The present data are the first to demonstrate, in vivo, neuronal regulation of

  1. Ultrastructural changes in neonatal sciatic nerve tissue: effects of passive maternal smoking.

    PubMed

    Amankwah, K S; Kaufmann, R C; Weberg, A D

    1985-01-01

    The dangers of cigarette smoking having already been recognized, this study attempts to delineate findings from a passive smoking study at the ultrastructural level. The project utilized a model of mice subjected to cigarette smoke and encompassed the electron microscopic examination of neonatal tissue for morphological abnormalities. Study of sciatic nerve tissue taken from the offspring of passively smoked females revealed definite toxic effects on the neonatal tissue. This investigation, which concentrated on morphological changes, indicates that passive maternal smoke inhalation may result in abnormal changes to the fine structure of fetal tissue although further investigation in this area is necessary to broaden our knowledge and understanding of the mechanisms involved.

  2. Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome.

    PubMed

    Sederholm, Benson H

    2010-09-01

    Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.

  3. The spatiotemporal localization of JAM-C following sciatic nerve crush in adult rats.

    PubMed

    Avari, Parizad; Huang, Wenlong; Averill, Sharon; Colom, Bartomeu; Imhof, Beat A; Nourshargh, Sussan; Priestley, John V

    2012-07-01

    JAM-C is a junctional adhesion molecule, enriched at tight junctions on endothelial and epithelial cells, and also localized to Schwann cells at junctions between adjoining myelin end loops. The role of JAM-C following peripheral nerve injury (PNI) is currently unknown. We examined the localization of JAM-C after sciatic nerve crush injury in adult rats. JAM-C immunoreactivity was present in paranodes and incisures in sham surgery control nerve, but distal to the crush injury significantly decreased at three and 14 days. JAM-C was re-expressed at 28 days and, by 56 days, was significantly increased in the distal nerve compared to controls. In a 7-mm length of sciatic nerve sampled distal to the crush site, the densities of JAM-C immunoreactive paranodes increased in the distal direction. Conversely, the densities of JAM-C immunoreactive incisures were highest immediately distal to the crush site and decreased in the more distal direction. Further analysis revealed a strong correlation between JAM-C localization and remyelination. Fifty-six days after crush injury, greater densities of JAM-C paranodes were seen compared to the nodal marker jacalin, suggesting that paranodal JAM-C precedes node formation. Our data are the first to demonstrate a potential role of JAM-C in remyelination after PNI.

  4. Structural protein transport in elongating motor axons after sciatic nerve crush. Effect of a conditioning lesion.

    PubMed

    McQuarrie, I G

    1986-12-01

    In elongating motor axons of the rat sciatic nerve, the maximum outgrowth rate increased from 4.6 to 5.3 mm/d (5.3-6.1 X 10(-8) m/s) when a testing lesion of spinal nerves L4 and L5 was preceded 2 wk earlier by a conditioning lesion of the sciatic nerve. Axonal outgrowth was examined by measuring the transport of 35[S]methionine-labeled structural proteins (tubulin, actin, and neurofilament triplet) from "parent" axon stumps into "daughter" axon sprouts. Since these proteins are conveyed by the slow component of axonal transport at 1-5 mm/d (1.2-6.0 X 10(-8) m/s), the isotope was injected into the spinal cord 1 wk before the testing lesion. Nerves were removed 8 d after the testing lesion, sectioned into 3-mm segments, and homogenized; soluble proteins were separated by polyacrylamide gel electrophoresis. Fluorographs were used as templates to identify gel segments for removal, solubilization, and liquid scintillation counting. Distributions of mean radioactivity for tubulin, actin, and neurofilament triplet were plotted for animals receiving a conditioning vs sham-conditioning lesion. Greater amounts of tubulin and actin were transported into daughter axons in the conditioned group. Tubulin was mainly increased in axon shafts, whereas actin was mainly increased in axon tips. These findings suggest that the axonal transport of tubulin and actin governs the rate of elongation.

  5. Electric stimulation and decimeter wave therapy improve the recovery of injured sciatic nerves

    PubMed Central

    Zhao, Feng; He, Wei; Zhang, Yingze; Tian, Dehu; Zhao, Hongfang; Yu, Kunlun; Bai, Jiangbo

    2013-01-01

    Drug treatment, electric stimulation and decimeter wave therapy have been shown to promote the repair and regeneration of the peripheral nerves at the injured site. This study prepared a Mackinnon's model of rat sciatic nerve compression. Electric stimulation was given immediately after neurolysis, and decimeter wave radiation was performed at 1 and 12 weeks post-operation. Histological observation revealed that intraoperative electric stimulation and decimeter wave therapy could improve the local blood circulation of repaired sites, alleviate hypoxia of compressed nerves, and lessen adhesion of compressed nerves, thereby decreasing the formation of new entrapments and enhancing compressed nerve regeneration through an improved microenvironment for regeneration. Immunohistochemical staining results revealed that intraoperative electric stimulation and decimeter wave could promote the expression of S-100 protein. Motor nerve conduction velocity and amplitude, the number and diameter of myelinated nerve fibers, and sciatic functional index were significantly increased in the treated rats. These results verified that intraoperative electric stimulation and decimeter wave therapy contributed to the regeneration and the recovery of the functions in the compressed nerves. PMID:25206506

  6. Sciatic nerve regeneration using a nerve growth factor-containing fibrin glue membrane.

    PubMed

    Ma, Shengzhong; Peng, Changliang; Wu, Shiqing; Wu, Dongjin; Gao, Chunzheng

    2013-12-25

    Our previous findings confirmed that the nerve growth factor-containing fibrin glue membrane provides a good microenvironment for peripheral nerve regeneration; however, the precise mechanism remains unclear. p75 neurotrophin receptor (p75(NTR)) plays an important role in the regulation of peripheral nerve regeneration. We hypothesized that a nerve growth factor-containing fibrin glue membrane can promote neural regeneration by up-regulating p75(NTR) expression. In this study, we used a silicon nerve conduit to bridge a 15 mm-long sciatic nerve defect and injected a mixture of nerve growth factor and fibrin glue at the anastomotic site of the nerve conduit and the sciatic nerve. Through RT-PCR and western blot analysis, nerve growth factor-containing fibrin glue membrane significantly increased p75(NTR) mRNA and protein expression in the Schwann cells at the anastomotic site, in particular at 8 weeks after injection of the nerve growth factor/fibrin glue mixture. These results indicate that nerve growth factor-containing fibrin glue membrane can promote peripheral nerve regeneration by up-regulating p75(NTR) expression in Schwann cells.

  7. Effect of mutated defensin NP-1 on sciatic nerve regeneration after transection--A pivot study.

    PubMed

    Xu, Chungui; Bai, Lili; Chen, Yuhong; Fan, Chengming; Hu, Zanmin; Xu, Hailin; Jiang, Baoguo

    2016-03-23

    Defensins are small cationic peptides that constitute the first line of defense against pathogens and are involved in immune regulation. In this study, their role in peripheral nerve regeneration was investigated. Rat sciatic nerves were transected and the two nerve stumps were bridged by a chitin conduit with a gap of 5mm between the stumps. The animals were injected intramuscularly with mutated rabbit neutrophil peptide 1 (defensin mNP-1), the positive control nerve growth factor (NGF) or the negative control saline, for 7 consecutive days after repair. After 6 weeks, the sciatic functional index (SFI), MNCV (motor nerve conductive velocity) and morphological parameters including myelinated fiber amounts, fiber diameter, axon diameter, myelin thickness and G-ratio were measured. Compared to the SFI of saline group, the NGF and mNP-1 groups had an increase of 18.3% and 18.8%, respectively. The numbers of myelinated fibers in the distal nerve of NGF and mNP-1 groups were 1.45- and 1.32-fold higher than in the saline group. The MNCVs of NGF and mNP-1 groups were 7.3 and 4.4 times of that of saline group. Fiber diameter, axon diameter, myelin thickness and G-ratio in the NGF and mNP-1 groups were also significantly higher than those of saline group. Our results demonstrate that, like NGF, the defensin mNP-1 can promote regeneration after a peripheral nerve cut.

  8. Application of implantable wireless biomicrosystem for monitoring nerve impedance of rat after sciatic nerve injury.

    PubMed

    Li, Yu-Ting; Peng, Chih-Wei; Chen, Lung-Tai; Lin, Wen-Shan; Chu, Chun-Hsun; Chen, Jia-Jin Jason

    2013-01-01

    Electrical stimulation is usually applied percutaneously for facilitating peripheral nerve regeneration. However, few studies have conducted long-term monitoring of the condition of nerve regeneration. This study implements an implantable biomicrosystem for inducing pulse current for aiding nerve repair and monitoring the time-course changes of nerve impedance for assessing nerve regeneration in sciatic nerve injury rat model. For long-term implantation, a transcutaneous magnetic coupling technique is adopted for power and data transmission. For in vivo study, the implanted module was placed in the rat's abdomen and the cuff electrode was wrapped around an 8-mm sciatic nerve gap of the rat for nerve impedance measurement for 42 days. One group of animals received monophasic constant current via the cuff electrode and a second group had no stimulation between days 8-21. The nerve impedance increased to above 150% of the initial value in the nerve regeneration groups with and without stimulation whereas the group with no nerve regeneration increased to only 113% at day 42. The impedance increase in nerve regeneration groups can be observed before evident functional recovery. Also, the nerve regeneration group that received electrical stimulation had relatively higher myelinated fiber density than that of no stimulation group, 20686 versus 11417 fiber/mm (2). The developed implantable biomicrosystem is proven to be a useful experimental tool for long-term stimulation in aiding nerve fiber growth as well as impedance assessment for understanding the time-course changes of nerve regeneration.

  9. N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury.

    PubMed

    Witzel, Christian; Reutter, Werner; Stark, G Björn; Koulaxouzidis, Georgios

    2015-06-01

    Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp) increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg) or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection). ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005) and the number of arborizing axons (21% vs. 16%; P = 0.008) 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration.

  10. N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury

    PubMed Central

    Witzel, Christian; Reutter, Werner; Stark, G. Björn; Koulaxouzidis, Georgios

    2015-01-01

    Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp) increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg) or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection). ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005) and the number of arborizing axons (21% vs. 16%; P = 0.008) 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration. PMID:26199617

  11. Differential gene expression profiling and biological process analysis in proximal nerve segments after sciatic nerve transection.

    PubMed

    Li, Shiying; Liu, Qianqian; Wang, Yongjun; Gu, Yun; Liu, Dong; Wang, Chunming; Ding, Guohui; Chen, Jianping; Liu, Jie; Gu, Xiaosong

    2013-01-01

    After traumatic injury, peripheral nerves can spontaneously regenerate through highly sophisticated and dynamic processes that are regulated by multiple cellular elements and molecular factors. Despite evidence of morphological changes and of expression changes of a few regulatory genes, global knowledge of gene expression changes and related biological processes during peripheral nerve injury and regeneration is still lacking. Here we aimed to profile global mRNA expression changes in proximal nerve segments of adult rats after sciatic nerve transection. According to DNA microarray analysis, the huge number of genes was differentially expressed at different time points (0.5 h-14 d) post nerve transection, exhibiting multiple distinct temporal expression patterns. The expression changes of several genes were further validated by quantitative real-time RT-PCR analysis. The gene ontology enrichment analysis was performed to decipher the biological processes involving the differentially expressed genes. Collectively, our results highlighted the dynamic change of the important biological processes and the time-dependent expression of key regulatory genes after peripheral nerve injury. Interestingly, we, for the first time, reported the presence of olfactory receptors in sciatic nerves. Hopefully, this study may provide a useful platform for deeply studying peripheral nerve injury and regeneration from a molecular-level perspective.

  12. Prenatal exposure to low levels of carbon monoxide alters sciatic nerve myelination in rat offspring.

    PubMed

    Carratù, M R; Cagiano, R; Desantis, S; Labate, M; Tattoli, M; Trabace, L; Cuomo, V

    2000-08-25

    Prenatal exposure to low concentrations of carbon monoxide (CO, 75 and 150 ppm from day 0 to day 20 of gestation), resulting in maternal blood HbCO concentrations equivalent to those maintained by human cigarette smokers, leads to subtle myelin alterations in the sciatic nerve of male rat offspring. The rapid growth spurt in pup body weight was related to the period of maximal increase in myelin sheath thickness in both control and CO-exposed animals. A significant reduction in myelin sheath thickness of sciatic nerve fibers, paralleled by changes in the frequency distribution, occurred in both 40- and 90-day-old rats exposed in utero to CO (75 and 150 ppm). Myelin deficit observed in 75 and 150 ppm CO-exposed animals showed up only after the major spurt in myelination but not early during development. The subtle myelin alterations observed in CO-exposed offspring were not accompanied by changes in developmental pattern of axon diameters and did not result in a gross impairment of motor activity. These results suggest that the myelination process is selectively targeted by a prenatal exposure model simulating the CO exposure observed in human cigarette smokers.

  13. Wallerian degeneration and axonal regeneration after sciatic nerve crush are altered in ICAM-1-deficient mice.

    PubMed

    Kirsch, Matthias; Campos Friz, Marianella; Vougioukas, Vassilios I; Hofmann, Hans-Dieter

    2009-10-01

    The intercellular cell adhesion molecule-1 (ICAM-1) has been implicated in the recruitment of immune cells during inflammatory processes. Previous studies investigating its involvement in the process of Wallerian degeneration and focusing on its potential role in macrophage recruitement have come to controversial conclusions. To examine whether Wallerian degeneration is altered in the absence of ICAM-1, we have analyzed changes in the expression of axonal and Schwann cell markers following sciatic nerve crush in wildtype and ICAM-1-deficient mice. We report that the lack of ICAM-1 leads to impaired axonal degeneration and regeneration and to alterations in Schwann cell responses following sciatic nerve crush. Degradation of neurofilament protein, the collapse of axonal profiles, and the re-expression of neurofilament proteins are substantially delayed in the distal nerve segment of ICAM-1(-/-) mice. In contrast, the degradation of myelin, as determined by immunostaining for myelin protein zero, is unaltered in the mutants. Upregulation of GAP-43 and p75 neurotrophin receptor (p75(NTR)) expression, characteristic for Schwann cells dedifferentiating in response to nerve injury, is differentially altered in the mutant animals. These results indicate that ICAM-1 is essential for the normal progression of axonal degeneration and regeneration in distal segments of injured peripheral nerves.

  14. ERK1/2-mediated Schwann cell proliferation in the regenerating sciatic nerve by treadmill training.

    PubMed

    Seo, Tae Beom; Oh, Myung-Jin; You, Byoung-Gun; Kwon, Ku-Birm; Chang, In-Ae; Yoon, Jin-Hwan; Lee, Chan-Yong; Namgung, Uk

    2009-10-01

    Proliferation of Schwann cells in the injured peripheral nerve supports axonal regeneration, and physical training in experimental animals has been shown to promote nerve regeneration. Extracellular signal-regulated kinase 1/2 (ERK1/2) activity can mediate neuronal responses to lesion signals, but its role in non-neuronal cells in the injured area is largely unknown. Here we report that treadmill training (TMT) facilitates axonal regeneration via the upregulation of phospho-ERK1/2 protein levels in Schwann cells in the injured sciatic nerve. Low-intensity, but not high-intensity, TMT increased neurite outgrowth of dorsal root ganglion (DRG) sensory neurons and potentiated Schwann cell proliferation. TMT elevated levels of GAP-43 mRNA and protein, and phospho-ERK1/2 protein in the injured sciatic nerves. TMT also enhanced phospho-c-Jun protein levels in the injured nerve. In-vivo administration of the ERK1/2 inhibitor PD98059 eliminated phospho-c-Jun, suggesting ERK1/2 phosphorylation of the c-Jun protein. PD98059 treatment decreased levels of BrdU-labeled proliferating Schwann cells in the distal portion of the injured nerve, and delayed the axonal regrowth that was promoted by TMT. The present data suggest that increased ERK1/2 activity in Schwann cells may play an important role in TMT-mediated enhancement of axonal regeneration in the injured peripheral nerve.

  15. Novel polysaccharide-derived hydrogel prevents perineural adhesions in a rat model of sciatic nerve adhesion.

    PubMed

    Yamamoto, Michiro; Endo, Nobuyuki; Ito, Masaya; Okui, Nobuyuki; Koh, Shukuki; Kaneko, Hiroaki; Hirata, Hitoshi

    2010-03-01

    We investigated the effects of a novel carboxymethylcellulose (CMC)-derived hydrogel, in which phosphatidylethanolamine (PE) was introduced into the carboxyl groups of CMC, for preventing perineural adhesion after extensive internal neurolysis of rat sciatic nerve. Sciatic nerves were randomly assigned to one of the following groups: the Control group, operated but no treatment; the HA group, operated and treated with 1% hyaluronan; the CMC-PE(L) group, operated and treated with low-viscosity CMC-PE hydrogel; and the CMC-PE(H) group, operated and treated with high-viscosity CMC-PE hydrogel. Perineural adhesions were evaluated at 6 weeks. Nerves were also subjected to biomechanical testing to assess ultimate breaking strength. Electrophysiological and wet muscle weight measurements were performed. Breaking strengths were significantly lower for the CMC-PE(L) group than for the Control and HA groups. Latency was significantly longer for the Control group than for the CMC-PE(L) group at 20 days. The mean percentage of wet muscle weight to body weight was significantly lower for the Control group than for the CMC-PE(L) group at 6 weeks. Low-viscosity CMC-PE hydrogel appears to prevent perineural adhesions and allow early restoration of nerve function.

  16. [Occupational toxic neuropathies: morphology in peripheral nerve biopsies].

    PubMed

    Scelsi, Roberto; Candura, Stefano M

    2012-01-01

    Many peripheral neuropathies are caused by the (acute or chronic) toxic action of metals, solvents, pesticides, and other occupational and environmental contaminants. These agents often reproduce the anatomoclinical pictures of hereditary (e.g., Charcot-Marie-Tooth disease), autoimmune (Guillain-Barrè syndrome), or dysmetabolic (thiamine deficiency, diabetic neuropathy) forms. Toxic peripheral neuropathies can be classified on the basis of etiology, clinical features (sensitive, motor, sensitive-motor), or histopathology: neuronopathies (uncommon, mostly secondary to retrograde axonal degeneration; e.g., arsenic, thallium), axonopathies (acrylamide, esacarbons, CS2, organophosphate-induced delayed neuropathy), myelinopathies (trichloroethylene), mixed forms (axonal and demyelinating: lead). For many substances, experimental research has led to the identification of the molecular and cellular targets of neurotoxicity. Several compounds are active by biotransformation (e.g., the esacarbons n-hexane and MnBK are neurotoxic since they are metabolized to 2,5-hexanedione), Genetic, physiological and environmental factors determine the individual metabolic set-up, and they may give origin to differences in the workers' sensitivity. Cessation of exposure is often followed by (microscopically observable) regenerative phenomena and clinical improvement. The morphology of neuropathies can be studied through peripheral nerve biopsy. Samples of sural nerve (or other nervous trunks of the limbs), adequately fixed, sectioned, and stained, allow the observation of alterations in axonal fibres (e.g., giant-axonal neuropathy, dying back neuropathy), myelin (demyelination), Schwann cells, interstitium, and blood vessels; possible inflammatory infiltrates; fibre density; regenerative phenomena (growth cone, remyelination). In occupational medicine, biopsy is indicated when the anamnestic-clinical picture, laboratory tests, and instrumental exams leave doubts about the nature, type

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

    PubMed

    Ferrari, Luiz F; Levine, Jon D

    2010-09-01

    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 was PKCε-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 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.

  18. Diagnostic accuracy of laser evoked potentials in diabetic neuropathy.

    PubMed

    Di Stefano, G; La Cesa, S; Leone, C; Pepe, A; Galosi, E; Fiorelli, M; Valeriani, M; Lacerenza, M; Pergolini, M; Biasiotta, A; Cruccu, G; Truini, A

    2017-03-04

    Although the most widely agreed neurophysiological tool for investigating small fibre damage is laser evoked potential (LEP) recording, no study has documented its diagnostic accuracy. In this clinical, neurophysiological and skin biopsy study we collected age-corrected LEP normative ranges, verified the association of LEPs with pinprick sensory disturbances in the typical diabetic mixed-fibre polyneuropathy and assessed the sensitivity and specificity of LEPs in diabetic small-fibre neuropathy.From 288 LEP recordings from the face, hand and foot in 73 healthy subjects we collected age-corrected normative ranges for LEPs. We then selected 100 patients with mixed-fibre diabetic neuropathy and 25 patients with possible small-fibre diabetic neuropathy. In the 100 patients with mixed-fibre neuropathy we verified how LEP abnormalities were associated with clinically evident pinprick sensory disturbances. In the 25 patients with possible pure small-fibre neuropathy, using the skin biopsy for assessing the intraepidermal nerve fibre density, as a reference standard, we calculated LEP sensitivity and specificity.In healthy participants, age strongly influenced normative ranges for all LEP variables. By applying age-corrected normative ranges for LEPs, we found that LEPs were strongly associated with pinprick sensory disturbances. In relation to the skin biopsy findings, LEPs yielded 78% sensitivity and 81% specificity in the diagnosis of diabetic small-fibre neuropathy.Our study, providing age-corrected normative ranges for the main LEP data and their diagnostic accuracy, helps to make LEPs more reliable as a clinical diagnostic tool, and proposes this technique as a less invasive alternative to skin biopsy for diagnosing diabetic small-fibre neuropathy.

  19. Amelioration of Behavioural, Biochemical, and Neurophysiological Deficits by Combination of Monosodium Glutamate with Resveratrol/Alpha-Lipoic Acid/Coenzyme Q10 in Rat Model of Cisplatin-Induced Peripheral Neuropathy

    PubMed Central

    Sanji, Tejaswi; Madakasira Guggilla, Hariprasad; Razdan, Rema

    2013-01-01

    Cisplatin or cis-diamminedichloroplatinum (II) (CDDP) is a cytotoxic chemotherapeutic agent with dose-dependent peripheral neuropathy as a foremost side effect characterised by ataxia, pain, and sensory impairment. Cumulative drug therapy of CDDP is known to produce severe oxidative damage. It mainly targets and accumulates in dorsal root ganglia that in turn cause damage resulting in secondary nerve fibre axonopathy. In the present study, we investigated the neuroprotective effect of the combination of monosodium glutamate (MSG) with three individual antioxidants, that is, resveratrol, alpha-lipoic acid (ALA), and coenzyme Q10 (CoQ10), in cisplatin (2 mg/kg i.p. twice weekly) induced peripheral neuropathy in rats. After 8 weeks of treatment the degree of neuroprotection was determined by measuring behavioral and electrophysiological properties and sciatic nerve lipid peroxidation, as well as glutathione and catalase levels. The results suggested that pretreatment with the combination of MSG (500 mg/kg/day po) with resveratrol (10 mg/kg/day i.p.) or ALA (20 mg/kg/day i.p.) or CoQ10 (10 mg/kg weekly thrice i.p.) exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol. PMID:24489506

  20. Painless Ulcers and Fissures of Toes: Hereditary Sensory Neuropathy, Not Leprosy.

    PubMed

    Rao, Angoori Gnaneshwar

    2016-01-01

    Hereditary sensory neuropathies (HSN) are rare genetically determined neuropathies. They often manifest as painless injuries in children. We present HSN in a 5-year-old boy who presented with recurrent fissuring and ulceration involving both great toes.

  1. Painless Ulcers and Fissures of Toes: Hereditary Sensory Neuropathy, Not Leprosy

    PubMed Central

    Rao, Angoori Gnaneshwar

    2016-01-01

    Hereditary sensory neuropathies (HSN) are rare genetically determined neuropathies. They often manifest as painless injuries in children. We present HSN in a 5-year-old boy who presented with recurrent fissuring and ulceration involving both great toes. PMID:26955138

  2. Phenotypic variability of TRPV4 related neuropathies

    PubMed Central

    Evangelista, Teresinha; Bansagi, Boglarka; Pyle, Angela; Griffin, Helen; Douroudis, Konstantinos; Polvikoski, Tuomo; Antoniadi, Thalia; Bushby, Kate; Straub, Volker; Chinnery, Patrick F.; Lochmüller, Hanns; Horvath, Rita

    2015-01-01

    Mutations in the transient receptor potential vanilloid 4 (TRPV4) gene have been associated with autosomal dominant skeletal dysplasias and peripheral nervous system syndromes (PNSS). PNSS include Charcot–Marie–Tooth disease (CMT) type 2C, congenital spinal muscular atrophy and arthrogryposis and scapuloperoneal spinal muscular atrophy. We report the clinical, electrophysiological and muscle biopsy findings in two unrelated patients with two novel heterozygous missense mutations in the TRPV4 gene. Whole exome sequencing was carried out on genomic DNA using Illumina TruseqTM 62Mb exome capture. Patient 1 harbours a de novo c.805C > T (p.Arg269Cys) mutation. Clinically, this patient shows signs of both scapuloperoneal spinal muscular atrophy and skeletal dysplasia. Patient 2 harbours a novel c.184G > A (p.Asp62Asn) mutation. While the clinical phenotype is compatible with CMT type 2C with the patient's muscle harbours basophilic inclusions. Mutations in the TRPV4 gene have a broad phenotypic variability and disease severity and may share a similar pathogenic mechanism with Heat Shock Protein related neuropathies. PMID:25900305

  3. Nutritional optic neuropathy following bariatric surgery

    PubMed Central

    Sawicka-Pierko, Anna; Hady, Razak Hady; Mariak, Zofia; Dadan, Jacek

    2014-01-01

    Bariatric procedures, associated with gastrointestinal malabsorption of vitamins and microelements, may constitute a risk factor for nutritional optic neuropathy (NON). We present a case of a 34-year-old female patient who developed bilateral NON after sleeve gastrectomy. Despite postoperative ophthalmological supervision, 10 months after the procedure the woman presented with a bilateral decrease in visual acuity down to 0.8, bilateral visual field loss and abnormal visual evoked potential recordings. Laboratory abnormalities included decreased serum concentration of vitamin B12 (161 pg/ml). Treatment was based on intramuscular injections of vitamin B12 (1000 units per day). After 1 week of the treatment, we observed more than a three-fold increase in the serum concentration of vitamin B12 and resolution of the bilateral symptoms of NON. The incidence of NON is likely to increase due to the growing number of these bariatric procedures performed worldwide. Therefore, all persons subjected to such surgery should receive long-term ophthalmological follow-up and supplementation with vitamins and microelements. PMID:25562012

  4. A Role for Insulin in Diabetic Neuropathy

    PubMed Central

    Grote, Caleb W.; Wright, Douglas E.

    2016-01-01

    The peripheral nervous system is one of several organ systems that are profoundly affected in diabetes. The longstanding view is that insulin does not have a major role in modulating neuronal function in both central and peripheral nervous systems is now being challenged. In the setting of insulin deficiency or excess insulin, it is logical to propose that insulin dysregulation can contribute to neuropathic changes in sensory neurons. This is particularly important as sensory nerve damage associated with prediabetes, type 1 and type 2 diabetes is so prevalent. Here, we discuss the current experimental literature related to insulin's role as a potential neurotrophic factor in peripheral nerve function, as well as the possibility that insulin deficiency plays a role in diabetic neuropathy. In addition, we discuss how sensory neurons in the peripheral nervous system respond to insulin similar to other insulin-sensitive tissues. Moreover, studies now suggest that sensory neurons can also become insulin resistant like other tissues. Collectively, emerging studies are revealing that insulin signaling pathways are active contributors to sensory nerve modulation, and this review highlights this novel activity and should provide new insight into insulin's role in both peripheral and central nervous system diseases. PMID:28066166

  5. Levodopa, vitamins, ageing and the neuropathy of Parkinson's disease.

    PubMed

    Rajabally, Yusuf A; Martey, Jean

    2013-11-01

    Higher prevalence of neuropathy has been described in patients with Parkinson's disease (PD) in comparison with age and gender-matched controls. The cause of neuropathy may be levodopa-induced impairment of vitamin B12 metabolism, suggesting levodopa-naïve subjects should be unaffected. There may, however, be other yet unidentified determinants of neuropathy in PD. We screened 33 consecutive levodopa-naïve PD patients for neuropathy. Demographics, vitamin B12 and folate levels were studied. Findings were analyzed in the light of our previous available data on levodopa-treated PD patients. Four of 33 (12.1 %) levodopa-naïve PD patients were diagnosed with neuropathy. This compared to 13/36 (36.1 %) previously evaluated levodopa-treated patients (p = 0.027) and 3/37 controls (p = 0.7). Analysis of our whole PD cohort consisting of a total of 70 subjects, including levodopa-naïve and levodopa-treated patients, revealed that neuropathy correlated with use of levodopa (p = 0.041), cumulative levodopa exposure (p = 0.046), age at time of study (p = 0.005) and serum folate levels <10 μg/L (p = 0.003). There was no association of neuropathy with PD duration. Multivariate regression analysis showed that neuropathy was only independently associated with age (p = 0.016) and serum folate levels <10 μg/L (p = 0.012). We conclude that this study confirms the roles of levodopa usage and cumulative levodopa exposure in the neuropathy of PD. However, the effects of levodopa only appear contributory and are surpassed by age and lower folate levels. In view of the independent implication of lower folate levels, the need for preventative/protective supplementation including folate in addition to vitamin B12, probably irrespective of levodopa use, may deserve consideration in patients with PD.

  6. Curcumin upregulates S100 expression and improves regeneration of the sciatic nerve following its complete amputation in mice

    PubMed Central

    Liu, Guo-min; Xu, Kun; Li, Juan; Luo, Yun-gang

    2016-01-01

    The repair of peripheral nerve injury after complete amputation is difficult, and even with anastomosis, the rapid recovery of nerve function remains challenging. Curcumin, extracted from plants of the genus Curcuma, has been shown to have anti-oxidant and anti-inflammatory properties and to improve sciatic nerve crush injury in rats. Here, we determined whether curcumin had neuroprotective effects following complete peripheral nerve amputation injury. BALB/c mice underwent complete sciatic nerve amputation, followed by an immediate epineurium anastomosis. Mice were intragastrically administered curcumin at doses of 40 (high), 20 (moderate), and 10 mg/kg/d (low) for 1 week. We found that myelin in the mice of the high- and moderate-dose curcumin groups appeared with regular shape, uniform thickness, clear boundary, and little hyperplasia surrounding the myelin. High and moderate doses of curcumin markedly improved both action potential amplitude of the sciatic nerves and the conduction velocity of the corresponding motor neurons, and upregulated mRNA and protein expression of S100, a marker for Schwann cell proliferation, in L4–6 spinal cord segments. These results suggest that curcumin is effective in promoting the repair of complete sciatic nerve amputation injury and that the underlying mechanism may be associated with upregulation of S100 expression. PMID:27651779

  7. The addition of clonidine to bupivacaine in combined femoral-sciatic nerve block for anterior cruciate ligament reconstruction.

    PubMed

    Couture, Darren J; Cuniff, Heather M; Maye, John P; Pellegrini, Joseph

    2004-08-01

    Clonidine has been shown to prolong sensory analgesia when given as an adjunct to peripheral nerve blocks but has not been evaluated when given in conjunction with a femoral-sciatic nerve block. The purpose of this investigation was to determine whether the addition of clonidine to a femoral-sciatic nerve block would prolong the duration of sensory analgesia in groups of patients undergoing anterior cruciate ligament (ACL) reconstruction. This prospective, randomized, double-blind investigation was performed on 64 subjects undergoing ACL reconstruction. Patients were assigned randomly to receive a femoral-sciatic nerve block using 30 mL of 0.5% bupivacaine with 1:200,000 epinephrine (control group) or 30 mL of 0.5% bupivacaine with 1:200,000 epinephrine and 1 microg/kg of clonidine (experimental group). Variables measured included demographics, timed pain intensity measurements, postoperative analgesic consumption, duration of analgesia, and patient satisfaction. No significant differences were noted between groups for pain intensity scores, duration of sensory analgesia, postoperative analgesic requirements, or overall patient satisfaction. Both groups reported minimal amounts of postoperative pain and high analgesic satisfaction scores. Based on our results, we do not recommend the addition of clonidine to a femoral-sciatic nerve block when given to facilitate postoperative analgesia in patients undergoing ACL reconstruction.

  8. 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.

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

    PubMed

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

    2011-02-01

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

  10. Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments

    PubMed Central

    Tesfaye, Solomon; Boulton, Andrew J.M.; Dyck, Peter J.; Freeman, Roy; Horowitz, Michael; Kempler, Peter; Lauria, Giuseppe; Malik, Rayaz A.; Spallone, Vincenza; Vinik, Aaron; Bernardi, Luciano; Valensi, Paul

    2010-01-01

    Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13–18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs. PMID:20876709

  11. 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

  12. Cisplatin neuropathy. Risk factors, prognosis, and protection by WR-2721

    SciTech Connect

    Mollman, J.E.; Glover, D.J.; Hogan, W.M.; Furman, R.E.

    1988-06-01

    A prospective study of patients receiving cis-diaminedichloroplatin II (DDP) was carried out to determine if risk factors could be identified related to the patient's living habits or past medical history that would predict in which patients DDP neuropathy might develop. Sixty-nine patients receiving six different combinations of chemotherapeutic agents, including DDP were examined. Twenty-eight of these patients received DDP in combination with the radioprotective agent S-2-(3-aminopropylamino)-ethylphosporothioic acid (WR 2721). No risk factors were identified relating to personal habits or past medical history of the patients. However, patients receiving DDP (40 mg/m2) on 5 consecutive days had a significantly higher incidence of neuropathy. Patients receiving DDP in combination with WR 2721 had a significantly lower incidence of neuropathy, and the mean dose at onset was significantly higher than the mean dose at onset of neuropathy for all other groups. In addition, five of six patients who were available for long-term follow-up demonstrated nearly complete reversal of the signs and symptoms of neuropathy.

  13. 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

    2016-05-27

    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.

  14. Axonal neuropathy with neuromyotonia: there is a HINT

    PubMed Central

    Peeters, Kristien; Chamova, Teodora; Tournev, Ivailo

    2017-01-01

    Abstract Recessive mutations in the gene encoding the histidine triad nucleotide binding protein 1 (HINT1) were recently shown to cause a motor-predominant Charcot–Marie–Tooth neuropathy. About 80% of the patients exhibit neuromyotonia, a striking clinical and electrophysiological hallmark that can help to distinguish this disease and to guide diagnostic screening. HINT1 neuropathy has worldwide distribution and is particularly prevalent in populations inhabiting central and south-eastern Europe. With 12 different mutations identified in more than 60 families, it ranks among the most common subtypes of axonal Charcot–Marie–Tooth neuropathy. This article provides an overview of the present knowledge on HINT1 neuropathy with the aim to increase awareness and spur interest among clinicians and researchers in the field. We propose diagnostic guidelines to recognize and differentiate this entity and suggest treatment strategies to manage common symptoms. As a recent player in the field of hereditary neuropathies, the role of HINT1 in peripheral nerves is unknown and the underlying disease mechanisms are unexplored. We provide a comprehensive overview of the structural and functional characteristics of the HINT1 protein that may guide further studies into the molecular aetiology and treatment strategies of this peculiar Charcot–Marie–Tooth subtype. PMID:28007994

  15. Laser-Doppler Imaging in the Detection of Peripheral Neuropathy

    PubMed Central

    Illigens, Ben M.W.; Siepmann, Timo; Roofeh, Joe; Gibbons, Christopher H.

    2013-01-01

    Small fiber neuropathy is common in a number of systemic diseases and is often challenging to diagnose. Laser-Doppler Imaging (LDI) is a test of small fiber neurovascular function that can quantify the integrity of the vasomotor C-fiber mediated axon-reflex, but no standardized method of analysis exists. We developed a novel LDI analysis technique and tested it in a human model of small fiber neuropathy. Eighteen healthy subjects (age 24±3 years) underwent LDI testing to assess the axon-mediated flare area in response to 10% acetylcholine iontophoresis. LDI measurements were taken before and longitudinally after a 48-hour application of 0.1% capsaicin (to cause a transient small fiber neuropathy) on the skin of the thigh; placebo cream was placed on the contralateral thigh as a control. We compared our new LDI image analysis technique to two previously published methods. The new LDI analysis technique was the only method to show a consistent difference in axon-reflex area between capsaicin treated and placebo treated skin on all testing days (p<0.05) with maximum attenuation of the flare area immediately post-application (438 ±298 mm2 vs. 824 ±375 mm2, p<0.05). In conclusion, this study demonstrates that our novel flare area method for LDI analysis can detect neurovascular dysfunction in a model of small fiber neuropathy, is an improvement over existing methods, and may supplement clinical assessment of small fiber neuropathy. PMID:23850386

  16. Laser Doppler imaging in the detection of peripheral neuropathy.

    PubMed

    Illigens, Ben M W; Siepmann, Timo; Roofeh, Joseph; Gibbons, Christopher H

    2013-10-01

    Small fiber neuropathy is common in a number of systemic diseases and is often challenging to diagnose. Laser Doppler imaging (LDI) is a test of small fiber neurovascular function that can quantify the integrity of the vasomotor C-fiber mediated axon-reflex, but no standardized method of analysis exists. We developed a novel LDI analysis technique and tested it in a human model of small fiber neuropathy. Eighteen healthy subjects (age 24 ± 3 years) underwent LDI testing to assess the axon-mediated flare area in response to 10% acetylcholine iontophoresis. LDI measurements were taken before and longitudinally after a 48-hour application of 0.1% capsaicin (to cause a transient small fiber neuropathy) on the skin of the thigh; placebo cream was placed on the contralateral thigh as a control. We compared our new LDI image analysis technique to two previously published methods. The new LDI analysis technique was the only method to show a consistent difference in axon-reflex area between capsaicin treated and placebo treated skin on all testing days (p<0.05) with maximum attenuation of the flare area immediately post-application (438 ± 298 mm(2) vs. 824 ± 375 mm(2), p<0.05). In conclusion, this study demonstrates that our novel flare area method for LDI analysis can detect neurovascular dysfunction in a model of small fiber neuropathy, is an improvement over existing methods, and may supplement clinical assessment of small fiber neuropathy.

  17. Clinical Approach to the Treatment of Painful Diabetic Neuropathy

    PubMed Central

    Hovaguimian, Alexandra; Gibbons, Christopher H.

    2011-01-01

    Painful neuropathy is a common and often progressive complication of diabetes. Patients frequently report symptoms of tingling, burning, lancinating pain, hyperesthesia, and allodynia. The natural history of the disease may vary from intermittent mild symptoms to severe chronic daily pain; the latter is often associated with diminished quality of life. There are a variety of pharmaceutical agents from different medicinal categories available for the symptomatic treatment of painful diabetic neuropathy, however selecting an agent is often challenging given the breadth of choices and lack of consistent guidelines. As a result, many patients remain untreated or undertreated. This article presents a practical clinical approach to the treatment of pain in diabetic neuropathy. Recommendations for first-, second-, and third-line medications are based on specific evidence for the treatment of painful diabetic neuropathy as well as safety, tolerability, drug interactions, and cost. Additional topics of discussion include breakthrough pain, opioid use, and topical therapies. This review does not comprehensively discuss all possible treatments for painful neuropathy, but provides a systematic approach designed to guide clinicians in tailoring therapies to the individual patient. PMID:21709806

  18. Clinical Approach to the Treatment of Painful Diabetic Neuropathy.

    PubMed

    Hovaguimian, Alexandra; Gibbons, Christopher H

    2011-02-01

    Painful neuropathy is a common and often progressive complication of diabetes. Patients frequently report symptoms of tingling, burning, lancinating pain, hyperesthesia and allodynia. The natural history of the disease may vary from intermittent mild symptoms to severe chronic daily pain; the latter is often associated with diminished quality of life. There are a variety of pharmaceutical agents from different medicinal categories available for the symptomatic treatment of painful diabetic neuropathy, however selecting an agent is often challenging given the breadth of choices and lack of consistent guidelines. As a result, many patients remain untreated or undertreated.This article presents a practical clinical approach to the treatment of pain in diabetic neuropathy. Recommendations for first, second and third line medications are based on specific evidence for the treatment of painful diabetic neuropathy as well as safety, tolerability, drug interactions and cost. Additional topics of discussion include breakthrough pain, opioid use and topical therapies. This review does not comprehensively discuss all possible treatments for painful neuropathy, but provides a systematic approach designed to guide clinicians in tailoring therapies to the individual patient.

  19. 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

  20. Animal Models of Peripheral Neuropathy Due to Environmental Toxicants

    PubMed Central

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

    2014-01-01

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

  1. Clinical and electrophysiological characteristics of neuropathy associated with Tangier disease.

    PubMed

    Zyss, Julie; Béhin, Anthony; Couvert, Philippe; Bouhour, Françoise; Sassolas, Agnès; Kolev, Ivan; Denys, Violaine; Vial, Christophe; Lacour, A; Carrié, Alain; Stojkovic, Tanya

    2012-06-01

    Tangier disease (TD) (OMIM#205400) is a rare autosomal recessive disorder resulting from mutations in the ABCA1 gene, leading to decreased levels of plasma high-density lipoproteins (HDL). Peripheral neuropathy is a common finding in this disease, and may present as relapsing/remitting mono/polyneuropathies or as syringomyelia-like neuropathy. We retrospectively analyzed four patients, and report here their clinical, biological, electrophysiological, imaging, and genetic findings. Three patients had a typical pseudosyringomyelic neuropathy including facial diplegia, but asymmetrical onset was observed in one patient who had first been misdiagnosed with Lewis-Sumner syndrome. Electrophysiological pattern was heterogeneous, showing both signs of demyelination and axonal degeneration. Truncating mutations of the ABCA1 gene, including two previously undescribed mutations, were constantly found. Atypical symptom onset and demyelinating features on electrophysiological examination can be misleading in case of pseudosyringomyelic neuropathy. These reports illustrate two different neurological phenotypes in TD, namely the pseudosyringomyelic type and the Lewis-Sumner-like type, and advocate for a systematic assessment of lipid profile including HDL cholesterol in demyelinating neuropathies.

  2. 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...

  3. Novel High-Throughput Drug Screening Platform for Chemotherapy-Induced Axonal Neuropathy

    DTIC Science & Technology

    2014-05-01

    13. SUPPLEMENTARY NOTES 14. ABSTRACT Chemotherapy-induced peripheral neuropathy (CIPN) is the most common dose-limiting neurotoxicity...10 Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is the most...and workloss burden of patients with chemotherapy-associated peripheral neuropathy in breast, ovarian, head and neck, and nonsmall cell lung cancer

  4. Facial neuropathy with imaging enhancement of the facial nerve: a case report

    PubMed Central

    Mumtaz, Sehreen; Jensen, Matthew B

    2014-01-01

    A young women developed unilateral facial neuropathy 2 weeks after a motor vehicle collision involving fractures of the skull and mandible. MRI showed contrast enhancement of the facial nerve. We review the literature describing facial neuropathy after trauma and facial nerve enhancement patterns with different causes of facial neuropathy. PMID:25574155

  5. Autotaxin and lysophosphatidic acid1 receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine

    PubMed Central

    2010-01-01

    Background Although neuropathic pain is frequently observed in demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis, the molecular basis for the relationship between demyelination and neuropathic pain behaviors is poorly understood. Previously, we found that lysophosphatidic acid receptor (LPA1) signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination. Results In the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG) down-regulation and damage of Schwann cell partitioning of C-fiber-containing Remak bundles in the sciatic nerve and dorsal root, but not in the spinal nerve. Demyelination, MAG down-regulation and Remak bundle damage in the dorsal root were abolished in LPA1 receptor-deficient (Lpar1-/-) mice, but these alterations were not observed in sciatic nerve. However, LPA-induced demyelination in ex vivo experiments was observed in the sciatic nerve, spinal nerve and dorsal root, all which express LPA1 transcript and protein. Nerve injury-induced dorsal root demyelination was markedly attenuated in mice heterozygous for autotaxin (atx+/-), which converts lysophosphatidylcholine (LPC) to LPA. Although the addition of LPC to ex vivo cultures of dorsal root fibers in the presence of recombinant ATX caused potent demyelination, it had no significant effect in the absence of ATX. On the other hand, intrathecal injection of LPC caused potent dorsal root demyelination, which was markedly attenuated or abolished in atx+/- or Lpar1-/- mice. Conclusions These results suggest that LPA, which is converted from LPC by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain. PMID:21062487

  6. Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections

    PubMed Central

    Panseri, Silvia; Cunha, Carla; Lowery, Joseph; Del Carro, Ubaldo; Taraballi, Francesca; Amadio, Stefano; Vescovi, Angelo; Gelain, Fabrizio

    2008-01-01

    Background Although many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways. In the last few decades tissue engineering has opened the door to new approaches;: however most of them make use of rigid channel guides that may cause cell loss due to the lack of physiological local stresses exerted over the nervous tissue during patient's movement. Electrospinning technique makes it possible to spin microfiber and nanofiber flexible tubular scaffolds composed of a number of natural and synthetic components, showing high porosity and remarkable surface/volume ratio. Results In this study we used electrospun tubes made of biodegradable polymers (a blend of PLGA/PCL) to regenerate a 10-mm nerve gap in a rat sciatic nerve in vivo. Experimental groups comprise lesioned animals (control group) and lesioned animals subjected to guide conduits implantated at the severed nerve stumps, where the tubular scaffolds are filled with saline solution. Four months after surgery, sciatic nerves failed to reconnect the two stumps of transected nerves in the control animal group. In most of the treated animals the electrospun tubes induced nervous regeneration and functional reconnection of the two severed sciatic nerve tracts. Myelination and collagen IV deposition have been detected in concurrence with regenerated fibers. No significant inflammatory response has been found. Neural tracers revealed the re-establishment of functional neuronal connections and evoked potential results showed the reinnervation of the target muscles in the majority of the treated animals. Conclusion Corroborating previous works, this study indicates that electrospun tubes, with no additional biological coating or drug loading treatment, are promising scaffolds for functional nervous regeneration. They can be knitted in meshes

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

    PubMed Central

    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.

    2015-01-01

    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. PMID:24934510

  8. 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.

  9. Drug-induced optic neuropathy-TB or not TB.

    PubMed

    Pradhan, Monika; Sharp, Dianne; Best, Stephen; Vincent, Andrea; Vaphiades, Michael

    2010-01-01

    Autosomal dominant optic atrophy is an inherited optic neuropathy manifesting with variable penetrance and expressivity. Other genetic and environmental factors are postulated to contribute to more marked visual loss in some affected individuals. Optic neuropathy is also a known adverse effect of ethambutol therapy for tuberculosis. This case report demonstrates an atypical presentation of ethambutol toxicity, with progressive profound loss of vision despite drug cessation. A subsequent diagnosis of autosomal dominant optic atrophy was made when the proband's sons presented with mild visual disturbances and color vision defects, confirmed with electrophysiology and OPA1 gene mutational analysis. This case emphasizes the importance of avoiding potentially neurotoxic therapy in predisposed individuals and the influence of environmental factors in patients with inherited optic neuropathies.

  10. Peripheral neuropathy in Whipples disease: a case report.

    PubMed

    Rusina, R; Keller, O; Síma, R; Zámečník, J

    2012-04-01

    Whipples disease is a chronic multisystem inflammatory disease with predominantly gastrointestinal manifestations due to Tropheryma whipplei infection. Typical neurological abnormalities include dementia, eye movement abnormalities, hypothalamic dysfunction and oculomasticatory myorhythmias. The literature on peripheral neuropathy in Whipples disease is sparse and the involvement of peripheral nerves in Whipples disease has not been documented convincingly so far. We present a case of Whipples disease presenting by axonal peripheral neuropathy without gastrointestinal involvement. The diagnosis was confirmed by a sural nerve biopsy and consequent PCR of the sample. All clinical signs disappeared progressively during the antibiotic therapy. Two years after the T. whipplei infection, the patient developed dopa-sensitive Parkinson's disease, although these two events seem to be unrelated. This case illustrates the value of peripheral nerve biopsy in cases of axonal neuropathy of unexplained origin and extends the clinical spectrum of Whipples disease to a new modality.

  11. Acute femoral neuropathy secondary to an iliacus muscle hematoma.

    PubMed

    Seijo-Martínez, M; Castro del Río, M; Fontoira, E; Fontoira, M

    2003-05-15

    We present a patient with a spontaneous iliacus muscle hematoma, appearing immediately after a minor physical maneuver, presenting with pain and femoral neuropathy initially evidenced by massive quadriceps muscle fasciculations. A magnetic resonance imaging (MRI) study of the pelvic area confirmed the diagnosis, showing a hematoma secondary to a partial muscle tear. The patient was managed conservatively, and the continuous muscle activity ceased in 3 days, with progressive improvement of the pain and weakness. The recovery was complete. Femoral neuropathy is uncommon and usually due to compression from psoas muscle mass lesions of diverse nature, including hematomas. Usually subacute, femoral neuropathy may present acutely in cases of large or strategically placed compressive femoral nerve lesions, and may require surgical evacuation. The case presented herein is remarkable since the muscle hematoma appeared after a nonviolent maneuver, fasciculations were present at onset, and conservative management was sufficient for a full recovery.

  12. 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.

  13. Is there treatment for Leber Hereditary Optic Neuropathy?

    PubMed Central

    Peragallo, Jason H.; Newman, Nancy J.

    2015-01-01

    Purpose of review To discuss recent advances in potential treatments for Leber hereditary optic neuropathy (LHON), a typically visually devastating hereditary optic neuropathy caused by mutations in the mitochondrial genome. Recent findings Idebenone has been proposed as a means of bypassing defective complex I activity and a free radical scavenger to prevent oxidative damage. EPI-743 may have more potency than idebenone, but no clinical trials have been performed. Gene therapy techniques have advanced significantly, including allotopic expression and nuclear transfer. Successful rescue of animal models of LHON with both of these therapies has been demonstrated. Introduction of exogenous DNA into the mitochondrial genome with mitochondrial targeting of viral vectors is another promising technique. Summary There are currently no proven treatments for Leber hereditary optic neuropathy. However, there are many promising novel treatment modalities that are currently being evaluated, with several clinical trials underway or in the planning stages. Supportive measures and genetic counseling remain of great importance for these patients. PMID:26448041

  14. 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.

  15. Ischemic-reperfusion of unilateral external iliac artery in rat: A new model for vasculitic femoral neuropathy.

    PubMed

    Muthuraman, Arunachalam; Ramesh, Muthusamy

    2016-08-15

    Clinically, ischemic environment during gynecological surgery at lithotomy position is most common causative factor for the development of vasculitic femoral neuropathy (VFN). The present study was designed to induce the clinically relevant rat model of VFN by ischemic-reperfusion (I/R) injury of unilateral external iliac artery (uEIA). The VFN was induced by 3, 4 and 5h occlusion of uEIA followed by reperfusion. The I/R of uEIA induced VFN was evaluated by (i) behavioral parameters i.e., hind limb temperature; weight bearing capacity; (ii) kinematic analysis i.e., paw posture, splay angle, static sciatic index (SSI), and ankle-angle tests; (iii) evaluation of pain perception i.e., plantar and pin prick; (iv) serum biochemical estimation i.e., nitrate, lipid peroxidation, TNF-α and calcium level; (v) evaluation of motor and sensory nerve conduction velocity; and (vi) measurement of nerve fiber density. The 4 and 5h occlusion of uEIA has produced the potential changes in behavioral, functional, electrophysiological, biochemical and histopathological assessment. The 5h occlusion of uEIA has shown to produce the mortality. Whereas, 3h occlusion does not produce the significant changes in the development of VFN. The 4h ischemic occlusion of uEIA has shown potential rat model of VFN due to its close mimicking capacity of VFN in human. Therefore, it can be useful to explore the newer anti-neuralgic medicine and with their pharmacodynamic action in the field of various neurovascular disorders.

  16. Therapeutic Effects of Fenofibrate on Diabetic Peripheral Neuropathy by Improving Endothelial and Neural Survival in db/db Mice

    PubMed Central

    Kim, Min Young; Kim, Tae Woo; Hong, Bo Young; Kim, Yong-Soo; Chang, Yoon Sik; Kim, Hye Won; Park, Cheol Whee

    2014-01-01

    Neural vascular insufficiency plays an important role in diabetic peripheral neuropathy (DPN). Peroxisome proliferative-activated receptor (PPAR)α has an endothelial protective effect related to activation of PPARγ coactivator (PGC)-1α and vascular endothelial growth factor (VEGF), but its role in DPN is unknown. We investigated whether fenofibrate would improve DPN associated with endothelial survival through AMPK-PGC-1α-eNOS pathway. Fenofibrate was given to db/db mice in combination with anti-flt-1 hexamer and anti-flk-1 heptamer (VEGFR inhibition) for 12 weeks. The db/db mice displayed sensory-motor impairment, nerve fibrosis and inflammation, increased apoptotic cells, disorganized myelin with axonal shrinkage and degeneration, fewer unmyelinated fibers, and endoneural vascular rarefaction in the sciatic nerve compared to db/m mice. These findings were exacerbated with VEGFR inhibition in db/db mice. Increased apoptotic cell death and endothelial dysfunction via inactivation of the PPARα-AMPK-PGC-1α pathway and their downstream PI3K-Akt-eNOS-NO pathway were noted in db/db mice, human umbilical vein endothelial cells (HUVECs) and human Schwann cells (HSCs) in high-glucose media. The effects were more prominent in response to VEGFR inhibition. In contrast, fenofibrate treatment ameliorated neural and endothelial damage by activating the PPARα-AMPK-PGC-1α-eNOS pathway in db/db mice, HUVECs and HSCs. Fenofibrate could be a promising therapy to prevent DPN by protecting endothelial cells through VEGF-independent activation of the PPARα-AMPK-PGC-1α-eNOS-NO pathway. PMID:24392081

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

    PubMed

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

    2014-06-01

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

  18. Ambient geothermal hydrogen sulfide exposure and peripheral neuropathy.

    PubMed

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

    2017-02-14

    The mechanism of toxicity of hydrogen sulfide (H2S) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether chronic exposure causes effects, including peripheral neuropathy, is yet unclear. The city of Rotorua, New Zealand, sits on an active geothermal field and the population has some of the highest measured ambient H2S exposures. A previous study in Rotorua provided evidence that H2S is associated with peripheral neuropathy. Using clinical methods, the present study sought to investigate and possibly confirm this association in the Rotorua population. The study population comprised 1635 adult residents of Rotorua, aged 18-65. Collected data relevant to the peripheral neuropathy investigation included symptoms, ankle stretch reflex, vibration sensitivity, as measured by the timed-tuning fork test and a Bio-Thesiometer (Bio-Medical Instrument Co., Ohio), and light touch sensitivity measured by monofilaments. An exposure metric, estimating time-weighted H2S exposure across the last 30 years was used. Principal components analysis was used to combine data across the various indicators of possible peripheral neuropathy. The main data analysis used linear regression to examine associations between the peripheral nerve function indicators and H2S exposure. None of the peripheral nerve function indicators were associated with H2S exposure, providing no evidence that H2S exposure at levels found in Rotorua is a cause of peripheral neuropathy. The earlier association between H2S exposure and peripheral neuropathy diagnoses may be attributable to the ecological study design used. The possibility that H2S exposure misclassification could account for the lack of association found cannot be entirely excluded.

  19. Towards a Diagnosis of Cochlear Neuropathy with Envelope Following Responses.

    PubMed

    Shaheen, Luke A; Valero, Michelle D; Liberman, M Charles

    2015-12-01

    Listeners with normal audiometric thresholds can still have suprathreshold deficits, for example, in the ability to discriminate sounds in complex acoustic scenes. One likely source of these deficits is cochlear neuropathy, a loss of auditory nerve (AN) fibers without hair cell damage, which can occur due to both aging and moderate acoustic overexposure. Since neuropathy can affect up to 50 % of AN fibers, its impact on suprathreshold hearing is likely profound, but progress is hindered by lack of a robust non-invasive test of neuropathy in humans. Reduction of suprathreshold auditory brainstem responses (ABRs) can be used to quantify neuropathy in inbred mice. However, ABR amplitudes are highly variable in humans, and thus more challenging to use. Since noise-induced neuropathy is selective for AN fibers with high thresholds, and because phase locking to temporal envelopes is particularly strong in these fibers, the envelope following response (EFR) might be a more robust measure. We compared EFRs to sinusoidally amplitude-modulated tones and ABRs to tone-pips in mice following a neuropathic noise exposure. EFR amplitude, EFR phase-locking value, and ABR amplitude were all reduced in noise-exposed mice. However, the changes in EFRs were more robust: the variance was smaller, thus inter-group differences were clearer. Optimum detection of neuropathy was achieved with high modulation frequencies and moderate levels. Analysis of group delays was used to confirm that the AN population was dominating the responses at these high modulation frequencies. Application of these principles in clinical testing can improve the differential diagnosis of sensorineural hearing loss.

  20. Methylprednisolone pulse therapy in severe dysthyroid optic neuropathy

    SciTech Connect

    Guy, J.R.; Fagien, S.; Donovan, J.P.; Rubin, M.L. )

    1989-07-01

    Five patients with severe dysthyroid optic neuropathy were treated with intravenous methylprednisolone (1 g daily for 3 consecutive days). Before administration, visual acuity of the more severely affected eyes of each patient was counting fingers at 5 feet, 8/200, 20/400, 20/200, and 20/80. Immediately after completion of pulse therapy, visual acuity improved to 20/25 in four patients and 20/30 in one. Remissions were maintained with oral prednisone and external beam irradiation of the orbit. Pulse methylprednisolone therapy appears to be beneficial in the initial management of severe dysthyroid optic neuropathy.