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Sample records for sciatic neuropathy

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

    PubMed Central

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

    2014-01-01

    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. PMID:25326571

  2. [Acute sciatic neuropathy--"post-Saturday palsy"].

    PubMed

    Manigoda, Miodrag; Dujmović-Basuroski, Irena; Trikić, Rajko; Drulović, Jelena

    2005-01-01

    This is a case report of 25-year old, unemployed male, admitted to hospital due to acute onset of the left foot drop, subsequent walking difficulty and numbness of the left calf and foot. Symptoms began after prolonged sleep with previous heroin abuse by sniffing. During neurological examination, mild weakness of knee flexors, moderate weakness of plantar flexors and paralysis of foot dorsiflexors, together with hypesthesia of the left calf, foot and fingers, predominantly in the innervation area of common peroneal nerve on the same side, were observed. The electrophysiologic examination revealed predominant involvement of peroneal division within the sciatic nerve, together with recorded conduction block indicating the compression as possible mechanism of nerve injury. The patient was administered corticosteroid therapy during two months, what resulted in almost complete recovery. The peculiarity of this case report is in the presence of the sciatic nerve "Saturday night palsy" with possible effect of former heroin abuse. PMID:16053177

  3. Diabetic neuropathy increases stimulation threshold during popliteal sciatic nerve block†

    PubMed Central

    Heschl, S.; Hallmann, B.; Zilke, T.; Gemes, G.; Schoerghuber, M.; Auer-Grumbach, M.; Quehenberger, F.; Lirk, P.; Hogan, Q.; Rigaud, M.

    2016-01-01

    Background Peripheral nerve stimulation is commonly used for nerve localization in regional anaesthesia, but recommended stimulation currents of 0.3–0.5 mA do not reliably produce motor activity in the absence of intraneural needle placement. As this may be particularly true in patients with diabetic neuropathy, we examined the stimulation threshold in patients with and without diabetes. Methods Preoperative evaluation included a neurological exam and electroneurography. During ultrasound-guided popliteal sciatic nerve block, we measured the current required to produce motor activity for the tibial and common peroneal nerve in diabetic and non-diabetic patients. Proximity to the nerve was evaluated post-hoc using ultrasound imaging. Results Average stimulation currents did not differ between diabetic (n=55) and non-diabetic patients (n=52). Although the planned number of patients was not reached, the power goal for the mean stimulation current was met. Subjects with diminished pressure perception showed increased thresholds for the common peroneal nerve (median 1.30 vs. 0.57 mA in subjects with normal perception, P=0.042), as did subjects with decreased pain sensation (1.60 vs. 0.50 mA in subjects with normal sensation, P=0.038). Slowed ulnar nerve conduction velocity predicted elevated mean stimulation current (r=−0.35, P=0.002). Finally, 15 diabetic patients required more than 0.5 mA to evoke a motor response, despite intraneural needle placement (n=4), or required currents ≥2 mA despite needle-nerve contact, vs three such patients (1 intraneural, 2 with ≥2 mA) among non-diabetic patients (P=0.003). Conclusions These findings suggest that stimulation thresholds of 0.3–0.5 mA may not reliably determine close needle-nerve contact during popliteal sciatic nerve block, particularly in patients with diabetic neuropathy. Clinical trial registration NCT01488474 PMID:26994231

  4. Isolated sciatic neuropathy as an initial manifestation of a high grade B-cell lymphoma: A case report and literature review.

    PubMed

    He, Wenzhuan; Wang, Weizhen; Gustas, Cristy; Malysz, Jozef; Kaur, Divpreet

    2016-10-01

    Sciatic nerve neuropathy due to infiltrating of a high grade B-cell lymphoma is a very rare situation and has not often been reported. We report a case with a previous history of indolent lymphoma who presented with isolated sciatic nerve neuropathy and was found to have diffuse large B cell lymphoma involving the sciatic nerve. Although the current case is not a primary sciatic nerve lymphoma given the systematic involvement shown on MRI and PET/CT scan, the case represents a neurolymphomatosis of the sciatic nerve given the direct invasion of the lymphoma cells into the sciatic nerve. Due to the rarity of this condition, we subsequently reviewed related literatures.

  5. 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.

  6. 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

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

    PubMed

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

    2016-01-01

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

  8. Isolated sciatic neuropathy as an initial manifestation of a high grade B-cell lymphoma: A case report and literature review.

    PubMed

    He, Wenzhuan; Wang, Weizhen; Gustas, Cristy; Malysz, Jozef; Kaur, Divpreet

    2016-10-01

    Sciatic nerve neuropathy due to infiltrating of a high grade B-cell lymphoma is a very rare situation and has not often been reported. We report a case with a previous history of indolent lymphoma who presented with isolated sciatic nerve neuropathy and was found to have diffuse large B cell lymphoma involving the sciatic nerve. Although the current case is not a primary sciatic nerve lymphoma given the systematic involvement shown on MRI and PET/CT scan, the case represents a neurolymphomatosis of the sciatic nerve given the direct invasion of the lymphoma cells into the sciatic nerve. Due to the rarity of this condition, we subsequently reviewed related literatures. PMID:27540756

  9. Metabolic Dysfunction Is Restricted to the Sciatic Nerve in Experimental Diabetic Neuropathy.

    PubMed

    Freeman, Oliver J; Unwin, Richard D; Dowsey, Andrew W; Begley, Paul; Ali, Sumia; Hollywood, Katherine A; Rustogi, Nitin; Petersen, Rasmus S; Dunn, Warwick B; Cooper, Garth J S; Gardiner, Natalie J

    2016-01-01

    High glucose levels in the peripheral nervous system (PNS) have been implicated in the pathogenesis of diabetic neuropathy (DN). However, our understanding of the molecular mechanisms that cause the marked distal pathology is incomplete. We performed a comprehensive, system-wide analysis of the PNS of a rodent model of DN. We integrated proteomics and metabolomics from the sciatic nerve (SN), the lumbar 4/5 dorsal root ganglia (DRG), and the trigeminal ganglia (TG) of streptozotocin-diabetic and healthy control rats. Even though all tissues showed a dramatic increase in glucose and polyol pathway intermediates in diabetes, a striking upregulation of mitochondrial oxidative phosphorylation and perturbation of lipid metabolism was found in the distal SN that was not present in the corresponding cell bodies of the DRG or the cranial TG. This finding suggests that the most severe molecular consequences of diabetes in the nervous system present in the SN, the region most affected by neuropathy. Such spatial metabolic dysfunction suggests a failure of energy homeostasis and/or oxidative stress, specifically in the distal axon/Schwann cell-rich SN. These data provide a detailed molecular description of the distinct compartmental effects of diabetes on the PNS that could underlie the distal-proximal distribution of pathology. PMID:26470786

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

    PubMed

    Zhang, Lei; Qu, Shen; Liang, Aibin; Jiang, Hong; Wang, Hao

    2015-02-01

    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

  11. 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

  12. MRI shows increased sciatic nerve cross sectional area in inherited and inflammatory neuropathies.

    PubMed

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

    2011-11-01

    Measurements of the cross sectional area of the sciatic nerve are described in a group of 10 patients with genetically confirmed Charcot-Marie-Tooth disease type 1A (CMT1A), nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 10 healthy controls using MRI. One mid-thigh of each individual was imaged using a short tau inversion recovery sequence and the nerve appearance evaluated radiologically with respect to the signal intensity and visibility of the internal neural structure. The cross sectional area of the sciatic nerve of each individual was measured by defining irregular enclosing regions of interest on the MRI images. The sciatic nerve area was enlarged in both CMT1A (p<0.001) and CIDP (p=0.008) compared with controls and in CMT1A compared with CIDP (p<0.001). Median (interquartile range) areas were 67.6 (16.2) mm(2) for the CIDP group, 135.9 (46.5) mm(2) for the CMT1A group and 43.3 (19.9) mm(2) for the control group. The critical upper value for discriminating pathologically enlarged nerves from normal controls with p<0.05 was 64.4 mm(2). Quantification of sciatic nerve hypertrophy on MRI may be of assistance in cases where the diagnosis is still in doubt, providing an objective pathological marker complimenting other clinical investigations.

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

    PubMed

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

    2016-01-15

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

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

    PubMed

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

    2016-01-15

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

  15. 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.

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

    PubMed

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

    2011-11-18

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

  17. Hereditary Neuropathies

    MedlinePlus

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

  18. Peripheral Neuropathy

    MedlinePlus

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

  19. [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.

  20. Diabetic Neuropathy

    MedlinePlus

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

  1. Metabolic neuropathies

    MedlinePlus

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

  2. Peripheral neuropathy

    MedlinePlus

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

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

    PubMed Central

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

    2010-01-01

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

  4. 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.

  5. Toxic neuropathies.

    PubMed

    Misra, Usha Kant; Kalita, Jayantee

    2009-01-01

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

  6. Neuropathy Tests

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Neuropathy Share this page: Was this page helpful? Overview | ... of testing are: To diagnose the presence of neuropathy and distinguish it from other conditions that may ...

  7. Peripheral Neuropathy

    MedlinePlus

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

  8. 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 ...

  9. [Sciatic nerve intraneural perineurioma].

    PubMed

    Bonhomme, Benjamin; Poussange, Nicolas; Le Collen, Philippe; Fabre, Thierry; Vital, Anne; Lepreux, Sébastien

    2015-12-01

    Intraneural perineurioma is a benign tumor developed from the perineurium and responsible for localized nerve hypertrophy. This uncommon tumor is characterized by a proliferation of perineural cells with a "pseudo-onion bulb" pattern. We report a sciatic nerve intraneural perineurioma in a 39-year-old patient. PMID:26586011

  10. 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

  11. Diabetic Neuropathies

    PubMed Central

    Russell, James W.; Zilliox, Lindsay A.

    2014-01-01

    Purpose of Review: This article provides an overview for understanding the diagnosis, pathogenesis, and management of diabetic neuropathy. Recent Findings: New information about the pathogenesis of diabetic neuropathy continues to emerge, which will lead to identifying new drug targets. It is clear that the natural history of diabetic neuropathy is changing and the rate of progression is slowing. This is likely because of a combination of earlier diagnosis, improved glycemic management, and improved control of related complications such as hyperlipidemia and hypertension. Early diagnosis is critical, and small fiber neuropathy or subclinical diabetic neuropathy may be reversed or significantly improved with appropriate intervention. The American Academy of Neurology recently published guidelines for the treatment of painful diabetic neuropathy. Summary: Diabetic neuropathy is common and can present with varied clinical presentations discussed in this article. Although treatment currently focuses on pain management, attention should be paid to potential risk factors for neuropathy. For example, glycemic control, hyperlipidemia, and hypertension should be managed with diet, exercise, and medications. Class I or II clinical studies indicate that pregabalin, duloxetine, amitriptyline, gabapentin, and opioids are effective in the management of diabetic neuropathic pain. PMID:25299279

  12. 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

  13. 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.

  14. 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

  15. Sciatic nerve injury related to hip replacement surgery: imaging detection by MR neurography despite susceptibility artifacts.

    PubMed

    Wolf, Marcel; Bäumer, Philipp; Pedro, Maria; Dombert, Thomas; Staub, Frank; Heiland, Sabine; Bendszus, Martin; Pham, Mirko

    2014-01-01

    Sciatic nerve palsy related to hip replacement surgery (HRS) is among the most common causes of sciatic neuropathies. The sciatic nerve may be injured by various different periprocedural mechanisms. The precise localization and extension of the nerve lesion, the determination of nerve continuity, lesion severity, and fascicular lesion distribution are essential for assessing the potential of spontaneous recovery and thereby avoiding delayed or inappropriate therapy. Adequate therapy is in many cases limited to conservative management, but in certain cases early surgical exploration and release of the nerve is indicated. Nerve-conduction-studies and electromyography are essential in the diagnosis of nerve injuries. In postsurgical nerve injuries, additional diagnostic imaging is important as well, in particular to detect or rule out direct mechanical compromise. Especially in the presence of metallic implants, commonly applied diagnostic imaging tests generally fail to adequately visualize nervous tissue. MRI has been deemed problematic due to implant-related artifacts after HRS. In this study, we describe for the first time the spectrum of imaging findings of Magnetic Resonance neurography (MRN) employing pulse sequences relatively insensitive to susceptibility artifacts (susceptibility insensitive MRN, siMRN) in a series of 9 patients with HRS procedure related sciatic nerve palsy. We were able to determine the localization and fascicular distribution of the sciatic nerve lesion in all 9 patients, which clearly showed on imaging predominant involvement of the peroneal more than the tibial division of the sciatic nerve. In 2 patients siMRN revealed direct mechanical compromise of the nerve by surgical material, and in one of these cases indication for surgical release of the sciatic nerve was based on siMRN. Thus, in selected cases of HRS related neuropathies, especially when surgical exploration of the nerve is considered, siMRN, with its potential to largely

  16. Autonomic neuropathies

    NASA Technical Reports Server (NTRS)

    Low, P. A.

    1998-01-01

    A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  19. 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

  20. [SUPRASCAPULAR NEUROPATHY].

    PubMed

    Massenet, V; Crielaard, J M

    2016-05-01

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

  1. Peripheral neuropathies.

    PubMed

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

    2016-01-01

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

  2. Transcriptomic analyses of genes and tissues in inherited sensory neuropathies.

    PubMed

    Sapio, Matthew R; Goswami, Samridhi C; Gross, Jacklyn R; Mannes, Andrew J; Iadarola, Michael J

    2016-09-01

    Inherited sensory neuropathies are caused by mutations in genes affecting either primary afferent neurons, or the Schwann cells that myelinate them. Using RNA-Seq, we analyzed the transcriptome of human and rat DRG and peripheral nerve, which contain sensory neurons and Schwann cells, respectively. We subdivide inherited sensory neuropathies based on expression of the mutated gene in these tissues, as well as in mouse TRPV1 lineage DRG nociceptive neurons, and across 32 human tissues from the Human Protein Atlas. We propose that this comprehensive approach to neuropathy gene expression leads to better understanding of the involved cell types in patients with these disorders. We also characterize the genetic "fingerprint" of both tissues, and present the highly tissue-specific genes in DRG and sciatic nerve that may aid in the development of gene panels to improve diagnostics for genetic neuropathies, and may represent specific drug targets for diseases of these tissues. PMID:27343803

  3. Giant Axonal Neuropathy

    MedlinePlus

    ... Diversity Find People About NINDS NINDS Giant Axonal Neuropathy Information Page Table of Contents (click to jump ... done? Clinical Trials Organizations What is Giant Axonal Neuropathy? Giant axonal neuropathy (GAN) is a rare inherited ...

  4. Multifocal Motor Neuropathy

    MedlinePlus

    ... Diversity Find People About NINDS NINDS Multifocal Motor Neuropathy Information Page Table of Contents (click to jump ... done? Clinical Trials Organizations What is Multifocal Motor Neuropathy? Multifocal motor neuropathy is a progressive muscle disorder ...

  5. Additional Types of Neuropathy

    MedlinePlus

    ... A A Listen En Español Additional Types of Neuropathy Charcot's Joint Charcot's Joint, also called neuropathic arthropathy, ... can stop bone destruction and aid healing. Cranial Neuropathy Cranial neuropathy affects the 12 pairs of nerves ...

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

    PubMed

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

    2014-09-01

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

  7. The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

    PubMed Central

    Yalcin, Ipek; Megat, Salim; Barthas, Florent; Waltisperger, Elisabeth; Kremer, Mélanie; Salvat, Eric; Barrot, Michel

    2014-01-01

    Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in injured sensory neurons and along the entire nociceptive pathway within the central nervous system. It is usually chronic and challenging to treat. In order to study neuropathic pain and its treatments, different models have been developed in rodents. These models derive from known etiologies, thus reproducing peripheral nerve injuries, central injuries, and metabolic-, infectious- or chemotherapy-related neuropathies. Murine models of peripheral nerve injury often target the sciatic nerve which is easy to access and allows nociceptive tests on the hind paw. These models rely on a compression and/or a section. Here, the detailed surgery procedure for the "cuff model" of neuropathic pain in mice is described. In this model, a cuff of PE-20 polyethylene tubing of standardized length (2 mm) is unilaterally implanted around the main branch of the sciatic nerve. It induces a long-lasting mechanical allodynia, i.e., a nociceptive response to a normally non-nociceptive stimulus that can be evaluated by using von Frey filaments. Besides the detailed surgery and testing procedures, the interest of this model for the study of neuropathic pain mechanism, for the study of neuropathic pain sensory and anxiodepressive aspects, and for the study of neuropathic pain treatments are also discussed. PMID:25078668

  8. The sciatic nerve cuffing model of neuropathic pain in mice.

    PubMed

    Yalcin, Ipek; Megat, Salim; Barthas, Florent; Waltisperger, Elisabeth; Kremer, Mélanie; Salvat, Eric; Barrot, Michel

    2014-07-16

    Neuropathic pain arises as a consequence of a lesion or a disease affecting the somatosensory system. This syndrome results from maladaptive changes in injured sensory neurons and along the entire nociceptive pathway within the central nervous system. It is usually chronic and challenging to treat. In order to study neuropathic pain and its treatments, different models have been developed in rodents. These models derive from known etiologies, thus reproducing peripheral nerve injuries, central injuries, and metabolic-, infectious- or chemotherapy-related neuropathies. Murine models of peripheral nerve injury often target the sciatic nerve which is easy to access and allows nociceptive tests on the hind paw. These models rely on a compression and/or a section. Here, the detailed surgery procedure for the "cuff model" of neuropathic pain in mice is described. In this model, a cuff of PE-20 polyethylene tubing of standardized length (2 mm) is unilaterally implanted around the main branch of the sciatic nerve. It induces a long-lasting mechanical allodynia, i.e., a nociceptive response to a normally non-nociceptive stimulus that can be evaluated by using von Frey filaments. Besides the detailed surgery and testing procedures, the interest of this model for the study of neuropathic pain mechanism, for the study of neuropathic pain sensory and anxiodepressive aspects, and for the study of neuropathic pain treatments are also discussed.

  9. 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.

  10. Reactive oxygen species (ROS) mediates non-freezing cold injury of rat sciatic nerve

    PubMed Central

    Geng, Zhiwei; Tong, Xiaoyan; Jia, Hongjuan

    2015-01-01

    Non-freezing cold injury is an injury characterized by neuropathy, developing when patients expose to cold environments. Reactive oxygen species (ROS) has been shown as a contributing factor for the non-freezing cold nerve injury. However, the detailed connections between non-freezing cold nerve injury and ROS have not been described. In order to investigate the relationship between non-freezing cold nerve injury and reactive oxygen species, we study the effects of two cooling methods-the continuous cooling and the intermittent cooling with warming intervals-on rat sciatic nerves. Specifically, we assess the morphological changes and ROS production of the sciatic nerves underwent different cooling treatments. Our data shows both types of cooling methods cause nerve injury and ROS production. However, despite of identical cooling degree and duration, the sciatic nerves processed by intermittent cooling with warming intervals present more ROS production, severer reperfusion injury and pathological destructions than the sciatic nerves processed by continuous cooling. This result indicates reactive oxygen species, as a product of reperfusion, facilitates non-freezing cold nerve injury. PMID:26629065

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

    PubMed

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

    2015-08-01

    Hyperalgesia, allodynia, delayed motor nerve conduction velocity, oxidative stress and axonal damage are signs and symptoms of chemotherapy induced peripheral neuropathy (CIPN). Present treatment/preventive strategies of CIPN are futile and the neuropathy may even lead to discontinuation of chemotherapy. In this study, we evaluated the protective effect of tetrahydrocurcumin (THC) 40 and 80mg/kg in experimental vincristine induced neuropathy in rats. Hyperalgesia was assessed by hot plate (thermal), Randall-Selitto (mechanical) test, allodynia was assessed by cold plate (thermal) test, functional loss was measured by sciatic function index, nociception was evaluated by formalin test. Neurophysiological recordings were carried out to assess motor nerve conduction velocity. Total calcium levels, oxidative stress and TNF-α was measured in sciatic nerve tissue homogenate to assess neuropathy. Histopathological changes was observed on sciatic nerve to assess the protective effect of THC against the vincristine. Pregabalin was used as a standard in this study. Rats administered with THC at 80mg/kg significantly attenuated the vincristine induced neuropathic pain manifestations which may be due to its multiple actions including anti-nociceptive, anti-inflammatory, neuroprotective, calcium inhibitory and antioxidant effect. This study delineates that THC can be a promising candidate for the prevention of CIPN by chemotherapeutic agents. PMID:26102012

  12. Proximal Sciatic Nerve Intraneural Ganglion Cyst

    PubMed Central

    Swartz, Karin R.; Wilson, Dianne; Boland, Michael; Fee, Dominic B.

    2009-01-01

    Intraneural ganglion cysts are nonneoplastic, mucinous cysts within the epineurium of peripheral nerves which usually involve the peroneal nerve at the knee. A 37-year-old female presented with progressive left buttock and posterior thigh pain. Magnetic resonance imaging revealed a sciatic nerve mass at the sacral notch which was subsequently revealed to be an intraneural ganglion cyst. An intraneural ganglion cyst confined to the proximal sciatic nerve has only been reported once prior to 2009. PMID:20069041

  13. [Genetics of neuropathies].

    PubMed

    Gess, B; Schirmacher, A; Young, P

    2013-02-01

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

  14. Peripheral Neuropathy: Symptoms and Signs

    MedlinePlus

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

  15. Inherited Peripheral Neuropathies

    PubMed Central

    Saporta, Mario A.; Shy, Michael E.

    2013-01-01

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

  16. Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

    PubMed

    Zochodne, D W; Ho, L T; Allison, J A

    1994-12-01

    Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy. PMID:7699389

  17. Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

    PubMed

    Zochodne, D W; Ho, L T; Allison, J A

    1994-12-01

    Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy.

  18. Painful Traumatic Trigeminal Neuropathy.

    PubMed

    Rafael, Benoliel; Sorin, Teich; Eli, Eliav

    2016-08-01

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

  19. 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

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

    PubMed

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

    2016-03-01

    Schwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth diseases, that are commonly associated with a process of demyelination. However, the early molecular events that trigger the demyelination program in these diseases remain unknown. Here, we used virally delivered fluorescent probes and in vivo time-lapse imaging in a mouse model of demyelination to investigate the underlying mechanisms of the demyelination process. We demonstrated that mitochondrial calcium released by voltage-dependent anion channel 1 (VDAC1) after sciatic nerve injury triggers Schwann cell demyelination via ERK1/2, p38, JNK, and c-JUN activation. In diabetic mice, VDAC1 activity was altered, resulting in a mitochondrial calcium leak in Schwann cell cytoplasm, thereby priming the cell for demyelination. Moreover, reduction of mitochondrial calcium release, either by shRNA-mediated VDAC1 silencing or pharmacological inhibition, prevented demyelination, leading to nerve conduction and neuromuscular performance recovery in rodent models of diabetic neuropathy and Charcot-Marie-Tooth diseases. Therefore, this study identifies mitochondria as the early key factor in the molecular mechanism of peripheral demyelination and opens a potential opportunity for the treatment of demyelinating peripheral neuropathies. PMID:26878172

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

    PubMed Central

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

    2016-01-01

    Schwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth diseases, that are commonly associated with a process of demyelination. However, the early molecular events that trigger the demyelination program in these diseases remain unknown. Here, we used virally delivered fluorescent probes and in vivo time-lapse imaging in a mouse model of demyelination to investigate the underlying mechanisms of the demyelination process. We demonstrated that mitochondrial calcium released by voltage-dependent anion channel 1 (VDAC1) after sciatic nerve injury triggers Schwann cell demyelination via ERK1/2, p38, JNK, and c-JUN activation. In diabetic mice, VDAC1 activity was altered, resulting in a mitochondrial calcium leak in Schwann cell cytoplasm, thereby priming the cell for demyelination. Moreover, reduction of mitochondrial calcium release, either by shRNA-mediated VDAC1 silencing or pharmacological inhibition, prevented demyelination, leading to nerve conduction and neuromuscular performance recovery in rodent models of diabetic neuropathy and Charcot-Marie-Tooth diseases. Therefore, this study identifies mitochondria as the early key factor in the molecular mechanism of peripheral demyelination and opens a potential opportunity for the treatment of demyelinating peripheral neuropathies. PMID:26878172

  2. 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.

  3. Traumatic optic neuropathy.

    PubMed

    Steinsapir, K D; Goldberg, R A

    1994-01-01

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

  4. Acetylator phenotype in diabetic neuropathy.

    PubMed

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

    1977-07-30

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

  5. Acute Sciatic Neuritis following Lumbar Laminectomy

    PubMed Central

    Hitchon, Patrick; Reddy, Chandan G.

    2014-01-01

    It is commonly accepted that the common cause of acute/chronic pain in the distribution of the lumbosacral nerve roots is the herniation of a lumbar intervertebral disc, unless proven otherwise. The surgical treatment of lumbar disc herniation is successful in radicular pain and prevents or limits neurological damage in the majority of patients. Recurrence of sciatica after a successful disc surgery can be due to many possible etiologies. In the clinical setting we believe that the term sciatica might be associated with inflammation. We report a case of acute sciatic neuritis presented with significant persistent pain shortly after a successful disc surgery. The patient is a 59-year-old female with complaint of newly onset sciatica after complete pain resolution following a successful lumbar laminectomy for acute disc extrusion. In order to manage the patient's newly onset pain, the patient had multiple pain management visits which provided minimum relief. Persistent sciatica and consistent physical examination findings urged us to perform a pelvic MRI to visualize suspected pathology, which revealed right side sciatic neuritis. She responded to the electrical neuromodulation. Review of the literature on sciatic neuritis shows this is the first case report of sciatic neuritis subsequent to lumbar laminectomy. PMID:25024708

  6. Hereditary sensory neuropathies.

    PubMed

    Auer-Grumbach, Michaela

    2004-05-01

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

  7. Dual Angiogenic and Neurotrophic Effects of Bone Marrow–Derived Endothelial Progenitor Cells on Diabetic Neuropathy

    PubMed Central

    Jeong, Jin-Ok; Kim, Mee-Ohk; Kim, Hyongbum; Lee, Min-Young; Kim, Sung-Whan; Ii, Masaaki; Lee, Jung-uek; Lee, Jiyoon; Choi, Yong Jin; Cho, Hyun-Jai; Lee, Namho; Silver, Marcy; Wecker, Andrea; Kim, Dong-Wook; Yoon, Young-sup

    2009-01-01

    Background Endothelial progenitor cells (EPCs) are known to promote neovascularization in ischemic diseases. Recent evidence suggested that diabetic neuropathy is causally related to impaired angiogenesis and deficient growth factors. Accordingly, we investigated whether diabetic neuropathy could be reversed by local transplantation of EPCs. Methods and Results We found that motor and sensory nerve conduction velocities, blood flow, and capillary density were reduced in sciatic nerves of streptozotocin-induced diabetic mice but recovered to normal levels after hind-limb injection of bone marrow–derived EPCs. Injected EPCs were preferentially and durably engrafted in the sciatic nerves. A portion of engrafted EPCs were uniquely localized in close proximity to vasa nervorum, and a smaller portion of these EPCs were colocalized with endothelial cells. Multiple angiogenic and neurotrophic factors were significantly increased in the EPC-injected nerves. These dual angiogenic and neurotrophic effects of EPCs were confirmed by higher proliferation of Schwann cells and endothelial cells cultured in EPC-conditioned media. Conclusions We demonstrate for the first time that bone marrow-derived EPCs could reverse various manifestations of diabetic neuropathy. These therapeutic effects were mediated by direct augmentation of neovascularization in peripheral nerves through long-term and preferential engraftment of EPCs in nerves and particularly vasa nervorum and their paracrine effects. These findings suggest that EPC transplantation could represent an innovative therapeutic option for treating diabetic neuropathy. PMID:19171856

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

    PubMed

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

    2007-09-01

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

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

    PubMed

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

    2016-05-01

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

  10. Electrodiagnosis of peripheral neuropathy.

    PubMed

    Ross, Mark A

    2012-05-01

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

  11. Permanent Peripheral Neuropathy

    PubMed Central

    Higgins, Elizabeth

    2014-01-01

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

  12. 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.

  13. 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

  14. Neurologic complication after anterior sciatic nerve block.

    PubMed

    Shah, Shruti; Hadzic, Admir; Vloka, Jerry D; Cafferty, Maureen S; Moucha, Calin S; Santos, Alan C

    2005-05-01

    The lack of reported complications related to lower extremity peripheral nerve blocks (PNBs) may be related to the relatively infrequent application of these techniques and to the fact that most such events go unpublished. Our current understanding of the factors that lead to neurologic complications after PNBs is limited. This is partly the result of our inability to conduct meaningful retrospective studies because of a lack of standard and objective monitoring and documentation procedures for PNBs. We report a case of permanent injury to the sciatic nerve after sciatic nerve block through the anterior approach and discuss mechanisms that may have led to the injury. Intraneural injection and nerve injury can occur in the absence of pain on injection and it may be heralded by high injection pressure (resistance).

  15. Beneficial effect of the Ca2+ antagonist, nimodipine, on existing diabetic neuropathy in the BB/Wor rat.

    PubMed Central

    Kappelle, A. C.; Biessels, G.; Bravenboer, B.; van Buren, T.; Traber, J.; de Wildt, D. J.; Gispen, W. H.

    1994-01-01

    1. Neuropathy is a frequently diagnosed complication of diabetes mellitus. Effective pharmacotherapy is not available. 2. The spontaneously diabetic BB/Wor rats develop secondary complications like neuropathy as do human diabetic patients. 3. BB/Wor rats treated with insulin via a subcutaneous implant show a significant impairment of sensory and motor nerve conduction velocity 6 weeks after the onset of diabetes mellitus. 4. Intraperitoneal treatment of diabetic BB/Wor rats with the Ca2+ antagonist, nimodipine (20 mg kg-1), from week 6 onwards every 48 h for a period of 6 weeks resulted in a significant increase of sensory and motor nerve conduction velocity. 5. Twelve weeks after the onset of diabetes mellitus BB/Wor rats show a 40% impairment of sciatic nerve blood flow as compared to the non-diabetic age-matched controls. Treatment with nimodipine (20 mg kg-1) from week 6 onwards significantly increased the sciatic nerve blood flow as compared to placebo-treated diabetic BB/Wor rats. 6. The adrenergic responsiveness of the vasa nervorum of the sciatic nerve to tyramine and phenylephrine was investigated as a parameter for autonomic neuropathy. 7. The fact that nimodipine treatment restored the reduced response to tyramine independently of the reduced postsynaptic phenylephrine responsiveness indicates that nimodipine improves adrenergic responsiveness mainly at the presynaptic level. PMID:8019766

  16. 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

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

    PubMed

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

    2013-08-01

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

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

    PubMed

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

    2016-08-26

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

  19. Ischemic optic neuropathy.

    PubMed

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

    2008-10-01

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

  20. Inherited peripheral neuropathy.

    PubMed

    Keller, M P; Chance, P F

    1999-01-01

    Hereditary disorders of the peripheral nerves constitute a group of frequently encountered neurological diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is genetically heterogeneous and characterized by demyelination with moderately to severely reduced nerve conduction velocities, absent muscle stretch reflexes and onion bulb formation. Genetic loci for CMT1 map to chromosome 17 (CMT1A), chromosome 1 (CMT1B), and another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1 B result from point mutations in the myelin protein zero (Po or MPZ) gene. The molecular defect in CMT1 C is unknown. Mutations in the early growth response 2 gene (EGR2) are also associated with demyelinating neuropathy. Other rare forms of demyelinating peripheral neuropathies map to chromosome 8q, 10q, and 11q. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is characterized by normal or mildly reduced nerve conduction velocity with decreased amplitude and axonal loss without hypertrophic features. One form of CMT2 maps to chromosome 1 p36 (CMT2A), another to chromosome 3p (CMT2B) and another to 7p (CMT2D). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset demyelinating polyneuropathy that may be associated with point mutations in either the PMP22 gene or the Po gene and shares considerable clinical and pathological features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced

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

    PubMed

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

    2015-09-01

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

  2. 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.

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

    PubMed

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

    2015-09-01

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

  4. Clinical description of toxic neuropathies.

    PubMed

    Little, Ann A; Albers, James W

    2015-01-01

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

  5. Acetylator phenotype in diabetic neuropathy.

    PubMed Central

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

    1977-01-01

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

  6. Mitochondria and peripheral neuropathies.

    PubMed

    Vital, Anne; Vital, Claude

    2012-12-01

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

  7. 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

  8. Urokinase Plasminogen Receptor and the Fibrinolytic Complex Play a Role in Nerve Repair after Nerve Crush in Mice, and in Human Neuropathies

    PubMed Central

    Rivellini, Cristina; Dina, Giorgia; Porrello, Emanuela; Cerri, Federica; Scarlato, Marina; Domi, Teuta; Ungaro, Daniela; Carro, Ubaldo Del; Bolino, Alessandra; Quattrini, Angelo; Comi, Giancarlo; Previtali, Stefano C.

    2012-01-01

    Remodeling of extracellular matrix (ECM) is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR) is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA) promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced nerve repair after sciatic nerve crush. This was a consequence of reduced fibrinolytic activity and increased deposition of endoneurial fibrin and vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural nerve biopsies from patients with peripheral neuropathies. We showed that neuropathies with defective regeneration had reduced fibrinolytic activity. On the contrary, neuropathies with signs of active regeneration displayed higher fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis may facilitate regeneration and outcome of peripheral neuropathies. PMID:22363796

  9. 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

  10. Genetics Home Reference: Leber hereditary optic neuropathy

    MedlinePlus

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

  11. Genetics Home Reference: ataxia neuropathy spectrum

    MedlinePlus

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

  12. Genetics Home Reference: small fiber neuropathy

    MedlinePlus

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

  13. Arsenical peripheral neuropathy.

    PubMed

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

    2010-02-01

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

  14. [Leber's hereditary optic neuropathy].

    PubMed

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

    2013-08-01

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

  15. Diabetic autonomic neuropathy.

    PubMed

    Clarke, B F; Ewing, D J; Campbell, I W

    1979-10-01

    This review attempts to outline the present understanding of diabetic autonomic neuropathy. The clinical features have been increasinly recognised but knowledge of the localization and morphology of the lesions and their pathogenesis remains fragmentary. A metabolic causation as postulated in somatic nerves accords best with clinical observations. Most bodily systems, particularly the cardiovascular, gastrointestinal and urogenital, are involved with added disturbances of thermoregulatory function and pupillary reflexes. Possible effects on neuroendocrine and peptidergic secretion and respiratory control await definition. Current interest centres around the development of a new generation of tests of autonomic nerve function that are simple, non-invasive, reproducible and allow precision in diagnosis and accurate quantitation. Most are based on cardiovascular reflexes and abnormality in them is assumed to reflect autonomic damage elsewhere. Probably no single test suffices and a battery of tests reflecting both parasympathetic and sympathetic function is preferable. Little is known of the natural history. The prevalence may be greater than previously suspected and although symptoms are mild in the majority, a few develop florid features. The relation of control and duration of diabetes to the onset and progression of autonomic neuropathy is not clearly established. Once tests of autonomic function become abnormal they usually remain abnormal. Symptomatic autonomic neuropathy carries a greatly increased mortality rate possibly due to indirect mechanisms such as renal failure and direct mechanisms such as cardio-resiratory arrest. Improved treatment of some of the more disabling symptoms has been possible in recent years. PMID:387501

  16. Choice of imaging modality in the diagnosis of sciatic hernia

    PubMed Central

    Labib, Peter L. Z.; Malik, Sohail N.

    2013-01-01

    Sciatic hernias are one of the rarest types of hernia and often pose diagnostic difficulty to clinicians. We report a case of an 80-year-old lady with a sciatic hernia who had a falsely negative computed tomography (CT) but was found to have a colonic hernia on ultrasonography. The authors recommend that for patients in which there is a high degree of clinical suspicion for a sciatic hernia and a negative CT, ultrasonography may be considered as a useful imaging modality to confirm the diagnosis. PMID:24968433

  17. 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.

  18. 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

    2015-10-01

    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. PMID:26054810

  19. 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

    2015-10-01

    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.

  20. 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

  1. Animal Models of Diabetic Neuropathy: Progress Since 1960s

    PubMed Central

    Islam, Md. Shahidul

    2013-01-01

    Diabetic or peripheral diabetic neuropathy (PDN) is one of the major complications among some other diabetic complications such as diabetic nephropathy, diabetic retinopathy, and diabetic cardiomyopathy. The use of animal models in the research of diabetes and diabetic complications is very common when rats and mice are most commonly used for many reasons. A numbers of animal models of diabetic and PDN have been developed in the last several decades such as streptozotocin-induced diabetic rat models, conventional or genetically modified or high-fat diet-fed C57BL/Ks (db/db) mice models, streptozotocin-induced C57BL6/J and ddY mice models, Chinese hamster neuropathic model, rhesus monkey PDN model, spontaneously diabetic WBN/Kob rat model, L-fucose-induced neropathic rat model, partial sciatic nerve ligated rat model, nonobese diabetic (NOD) mice model, spontaneously induced Ins2 Akita mice model, leptin-deficient (ob/ob) mice model, Otsuka Long-Evans Tokushima Fatty (OLETF) rat model, surgically-induced neuropathic model, and genetically modified Spontaneously Diabetic Torii (SDT) rat model, none of which are without limitations. An animal model of diabetic or PDN should mimic the all major pathogeneses of human diabetic neuropathy. Hence, this review comparatively evaluates the animal models of diabetic and PDN which are developed since 1960s with their advantages and disadvantages to help diabetic research groups in order to more accurately choose an appropriate model to meet their specific research objectives. PMID:23984428

  2. Characterization of a neuropathic pain model: sciatic cryoneurolysis in the rat.

    PubMed

    DeLeo, J A; Coombs, D W; Willenbring, S; Colburn, R W; Fromm, C; Wagner, R; Twitchell, B B

    1994-01-01

    Cryoanalgesia, the technique of freezing peripheral nerves, is used clinically for the treatment of postoperative and chronic pain. Paradoxically, this same technique produces characteristics in a rat model suggestive of neuropathic pain. We have developed a peripheral neuropathy model by freezing the proximal sciatic nerve (sciatic cryoneurolysis, SCN) using a cryoprobe cooled to -60 degrees C in a 30/5/30 sec freeze-thaw-freeze sequence. Each freeze cycle produced a transient ice ball on the surface of the nerve. These studies provide behavioral evidence that SCN is a valid mononeuropathy animal model. All animals demonstrate some degree of autotomy following SCN. The average onset of autotomy occurs 4 days postoperatively and peaks in severity and incidence at 14 days. By examining the latency of responses to a noxious heat stimulus, we have shown there is no direct relationship between an hypoesthetic paw and autotomy, i.e., autotomy did not occur immediately after the freeze lesion when the limb was dysfunctional. Rather, autotomy peaked when sensation was returning to the affected limb. The transient time course of certain behaviors including hypoesthesia and possible return of limb sensation, autotomy, touch-evoked allodynia, foot edema and the presence of spontaneous nociceptive behaviors demonstrate a multiple phase nociceptive process. The temporary nature of these nociceptive behaviors is in sharp contrast to the prolonged bilateral mechanical allodynia evident when these behaviors subside. The surgical anesthetics used during the SCN procedure are shown to variably alter or suppress autotomy following SCN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8159445

  3. 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.

  4. [Atypical neuropathies associated with diabetes].

    PubMed

    Lozeron, P

    2014-12-01

    Diabetes is the leading cause of neuropathy worldwide and, due to the epidemic progression of the affection, prevalence of diabetic neuropathies will increase in the near future. Beside the typical diabetic neuropathy pattern and the common entrapment neuropathies, several unusual clinical forms have been described with either a symmetrical or an asymmetrical pattern. Treatment-induced neuropathy is an acute sensory affection most commonly related to acute glycemic control. Pain is debilitating and associated with vegetative dysfunction. Prevention is important, as resolution is often incomplete. Several patterns or asymmetrical neuropathies of inflammatory and ischemic origin were described long ago in the lower limb. They are debilitating, most often painful and require steroid treatment. Other patterns affecting the thoracolumbar region or the upper limbs or involving a painless motor deficit must be identified as specific treatments are sometimes needed. An association between diabetes and chronic inflammatory demyelinating polyneuropathy has not been demonstrated but diagnosis may be suggested due to the misleading low conduction velocities seen in classical diabetic neuropathy. Like any other patient, the diabetic patient may present a neuropathy unrelated to diabetes. To facilitate patient care, neurologists should be aware of such clinical entities. PMID:25459114

  5. 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.

  6. 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.

  7. 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

  8. Cardiovascular autonomic neuropathy

    PubMed Central

    McCarty, Niamh

    2016-01-01

    Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this disease, including weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which occurred 2 years after his type 1 diabetes diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic hypotension, which suggests sympathetic denervation. He did not have complete cardiovascular autonomic reflex testing, which would have been helpful, but improved with aggressive diabetes treatment and the increase of beta-blockade. It is important to identify these patients to understand their signs and symptoms and consider appropriate therapies. PMID:27034552

  9. Cardiovascular autonomic neuropathy.

    PubMed

    McCarty, Niamh; Silverman, Barry

    2016-04-01

    Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this disease, including weakness, dizziness, fatigue, tachycardia, abnormal QTc, and orthostasis, which occurred 2 years after his type 1 diabetes diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic hypotension, which suggests sympathetic denervation. He did not have complete cardiovascular autonomic reflex testing, which would have been helpful, but improved with aggressive diabetes treatment and the increase of beta-blockade. It is important to identify these patients to understand their signs and symptoms and consider appropriate therapies. PMID:27034552

  10. 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).

  11. 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).

  12. 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

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

    PubMed

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

    2016-01-01

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

  14. 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. PMID:24790009

  15. 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).

  16. 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

  17. 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

  18. 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

  19. Multivesicular liposomal bupivacaine at the sciatic nerve.

    PubMed

    McAlvin, J Brian; Padera, Robert F; Shankarappa, Sahadev A; Reznor, Gally; Kwon, Albert H; Chiang, Homer H; Yang, Jason; Kohane, Daniel S

    2014-05-01

    Clinical translation of sustained release formulations for local anesthetics has been limited by adverse tissue reaction. Exparel™ (DepoFoam bupivacaine) is a new liposomal local anesthetic formulation whose biocompatibility near nerve tissue is not well characterized. Exparel™ injection caused sciatic nerve blockade in rats lasting 240 min compared to 120 min for 0.5% (w/v) bupivacaine HCl and 210 min for 1.31% (w/v) bupivacaine HCl (same bupivacaine content as Exparel™). On histologic sections four days after injection, median inflammation scores in the Exparel™ group (2.5 of 4) were slightly higher than in groups treated with bupivacaine solutions (score 2). Myotoxicity scores in the Exparel™ group (2.5 of 6) were similar to in the 0.5% (w/v) bupivacaine HCl group (3), but significantly less than in the 1.31% (w/v) bupivacaine HCl group (5). After two weeks, inflammation from Exparel™ (score 2 of 6) was greater than from 0.5% (w/v) bupivacaine HCl (1) and similar to that from 1.31% (w/v) bupivacaine HCl (1). Myotoxicity in all three groups was not statistically significantly different. No neurotoxicity was detected in any group. Tissue reaction to Exparel™ was similar to that of 0.5% (w/v) bupivacaine HCl. Surveillance for local tissue injury will be important during future clinical evaluation.

  20. 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.

  1. Indirect traumatic optic neuropathy.

    PubMed

    Singman, Eric L; Daphalapurkar, Nitin; White, Helen; Nguyen, Thao D; Panghat, Lijo; Chang, Jessica; McCulley, Timothy

    2016-01-01

    Indirect traumatic optic neuropathy (ITON) refers to optic nerve injury resulting from impact remote to the optic nerve. The mechanism of injury is not understood, and there are no confirmed protocols for prevention, mitigation or treatment. Most data concerning this condition comes from case series of civilian patients suffering blunt injury, such as from sports- or motor vehicle-related concussion, rather than military-related ballistic or blast damage. Research in this field will likely require the development of robust databases to identify patients with ITON and follow related outcomes, in addition to both in-vivo animal and virtual human models to study the mechanisms of damage and potential therapies. PMID:26759722

  2. 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.

  3. Suprascapular neuropathy in pitchers.

    PubMed

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

    1990-01-01

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

  4. [Leber's hereditary optic neuropathy].

    PubMed

    Leo-Kottler, B; Wissinger, B

    2011-12-01

    Leber's hereditary optic neuropathy (LHON) is a rare disease primarily affecting the retinal ganglion cells. In most cases patients with LHON develop permanent visual loss with a large central scotoma in the visual field of both eyes. The optic disc becomes partially or completely pale. At the onset of the disease many patients are considered to suffer from an optic neuritis and are treated under the diagnostic and therapeutic regimen of optic neuritis. LHON is mostly only considered when high dose cortisone therapy fails to be effective or the second eye is affected. Thereafter, molecular genetic analysis will prove LHON in these cases. Detailed anamnesis including pedigree analysis in combination with observance of the peripapillary microangiopathic alterations at the fundus will help to speed up the diagnosis of LHON, but even after exact clinical and molecular genetic diagnosis of LHON some aspects of the disease still remain a mystery today.

  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. PMID:22240103

  6. Peripheral Neuropathy and Agent Orange

    MedlinePlus

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

  7. 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.

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

    PubMed

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

    2013-04-15

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

  9. Histopathological effects of intramuscular metamizole sodium on rat sciatic nerve

    PubMed Central

    Emir, Abdurrahman; Kalkan, Yıldıray; Bostan, Habib

    2016-01-01

    Objective(s): We investigated the histopathological effects of metamizole sodium (MS) on the sciatic nerve. Materials and Methods: This study was performed using 48 adult male Wistar albino rats. Ten groups were constituted with 6 rats in each group. MS injection into the sciatic nerve (group 1), MS injection into the muscle [group 3 (50 mg/kg, 0.4 ml) and group 5 (50 mg/kg, 0.8 ml)], MS injection into the muscle cavity in the vicinity of the sciatic nerve [group 2 (50 mg/kg, 0.4 ml) and group 4 (50 mg/kg, 0.8 ml)], normal saline injection into the muscle in the vicinity of the sciatic nerve [group 6A (0.4 ml) and 6B (0.8 ml)], subjected to injury by drilling the entire layer of nerve without injecting any drug, normal saline injection in the sciatic nerve, and control group. Nerve and muscle samples were taken 7 days after administrations. Tissue sections were stained using a hematoxylin and eosin-Luxol® fast blue stain, assessed by a histologist. Results: The levels of axonal degeneration of the rats in groups 1, 2, 3, 4, 5, 6A, and 8 were found to be significantly higher compared to the levels of the rats in the control group (P<0.05). Myelin degeneration of the rats in all groups was found to be significantly higher compared to myelin degeneration of the rats in the control group (P<0.05). Conclusion: It was observed that MS could lead to injury in the sciatic nerve with a toxic effect due to diffusion. PMID:27746863

  10. 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

  11. 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

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

    PubMed

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

    2012-01-27

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

  13. 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

  14. Physical examination of upper extremity compressive neuropathies.

    PubMed

    Popinchalk, Samuel P; Schaffer, Alyssa A

    2012-10-01

    A thorough history and physical examination are vital to the assessment of upper extremity compressive neuropathies. This article summarizes relevant anatomy and physical examination findings associated with upper extremity compressive neuropathies.

  15. Mixed or immune complex cryoglobulinaemia and neuropathy

    PubMed Central

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

    1974-01-01

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

  16. Molecular basis of hereditary neuropathies.

    PubMed

    Chance, P F

    2001-05-01

    Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B) and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (P0 or MPZ) gene. The molecular defect in CMT1C is unknown. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy, also of undetermined cause. Forms of CMT2 map to chromosome 1p36 (CMT2A), chromosome 3p (CMT2B), chromosome 7p (CMT2D), and to chromosome 8p21 (CMT2E). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset, demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene or the P0 gene and shares considerable clinical and pathologic features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosomes 8q, 10q, and 11q. Hereditary neuralgic amyotrophy (familial brachial plexus neuropathy) is an autosomal dominant disorder causing painful, recurrent brachial plexopathies

  17. Nodes of Ranvier and Paranodes in Chronic Acquired Neuropathies

    PubMed Central

    Cifuentes-Diaz, Carmen; Dubourg, Odile; Irinopoulou, Theano; Vigny, Marc; Lachkar, Sylvie; Decker, Laurence; Charnay, Patrick; Denisenko, Natalia; Maisonobe, Thierry; Léger, Jean-Marc; Viala, Karine; Hauw, Jean-Jacques; Girault, Jean-Antoine

    2011-01-01

    Chronic acquired neuropathies of unknown origin are classified as chronic inflammatory demyelinating polyneuropathies (CIDP) and chronic idiopathic axonal polyneuropathies (CIAP). The diagnosis can be very difficult, although it has important therapeutic implications since CIDP can be improved by immunomodulating treatment. The aim of this study was to examine the possible abnormalities of nodal and paranodal regions in these two types of neuropathies. Longitudinal sections of superficial peroneal nerves were obtained from biopsy material from 12 patients with CIDP and 10 patients with CIAP and studied by immunofluorescence and in some cases electron microscopy. Electron microscopy revealed multiple alterations in the nodal and paranodal regions which predominated in Schwann cells in CIDP and in axons in CIAP. In CIDP paranodin/Caspr immunofluorescence was more widespread than in control nerves, extending along the axon in internodes where it appeared intense. Nodal channels Nav and KCNQ2 were less altered but were also detected in the internodes. In CIAP paranodes, paranodin labeling was irregular and/or decreased. To test the consequences of acquired primary Schwann cells alteration on axonal proteins, we used a mouse model based on induced deletion of the transcription factor Krox-20 gene. In the demyelinated sciatic nerves of these mice we observed alterations similar to those found in CIDP by immunofluorescence, and immunoblotting demonstrated increased levels of paranodin. Finally we examined whether the alterations in paranodin immunoreactivity could have a diagnosis value. In a sample of 16 biopsies, the study of paranodin immunofluorescence by blind evaluators led to correct diagnosis in 70±4% of the cases. This study characterizes for the first time the abnormalities of nodes of Ranvier in CIAP and CIDP, and the altered expression and distribution of nodal and paranodal proteins. Marked differences were observed between CIDP and CIAP and the alterations

  18. Nodes of ranvier and paranodes in chronic acquired neuropathies.

    PubMed

    Cifuentes-Diaz, Carmen; Dubourg, Odile; Irinopoulou, Theano; Vigny, Marc; Lachkar, Sylvie; Decker, Laurence; Charnay, Patrick; Denisenko, Natalia; Maisonobe, Thierry; Léger, Jean-Marc; Viala, Karine; Hauw, Jean-Jacques; Girault, Jean-Antoine

    2011-01-01

    Chronic acquired neuropathies of unknown origin are classified as chronic inflammatory demyelinating polyneuropathies (CIDP) and chronic idiopathic axonal polyneuropathies (CIAP). The diagnosis can be very difficult, although it has important therapeutic implications since CIDP can be improved by immunomodulating treatment. The aim of this study was to examine the possible abnormalities of nodal and paranodal regions in these two types of neuropathies. Longitudinal sections of superficial peroneal nerves were obtained from biopsy material from 12 patients with CIDP and 10 patients with CIAP and studied by immunofluorescence and in some cases electron microscopy. Electron microscopy revealed multiple alterations in the nodal and paranodal regions which predominated in Schwann cells in CIDP and in axons in CIAP. In CIDP paranodin/Caspr immunofluorescence was more widespread than in control nerves, extending along the axon in internodes where it appeared intense. Nodal channels Nav and KCNQ2 were less altered but were also detected in the internodes. In CIAP paranodes, paranodin labeling was irregular and/or decreased. To test the consequences of acquired primary Schwann cells alteration on axonal proteins, we used a mouse model based on induced deletion of the transcription factor Krox-20 gene. In the demyelinated sciatic nerves of these mice we observed alterations similar to those found in CIDP by immunofluorescence, and immunoblotting demonstrated increased levels of paranodin. Finally we examined whether the alterations in paranodin immunoreactivity could have a diagnosis value. In a sample of 16 biopsies, the study of paranodin immunofluorescence by blind evaluators led to correct diagnosis in 70 ± 4% of the cases. This study characterizes for the first time the abnormalities of nodes of Ranvier in CIAP and CIDP, and the altered expression and distribution of nodal and paranodal proteins. Marked differences were observed between CIDP and CIAP and the

  19. 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

  20. Lower limb surgeries under combined femoral and sciatic nerve block

    PubMed Central

    Bansal, Lipsy; Attri, Joginder Pal; Verma, Pawan

    2016-01-01

    Introduction: Peripheral nerve blocks are gaining popularity for many infraumblical surgeries with the development of new techniques such as ultrasound and peripheral nerve stimulator. It provides stable hemodynamic, better, and prolonged postoperative analgesia. This study was carried out to see the effectiveness of combined femoral and sciatic nerve block with ropivacaine alone and by adding fentanyl. Materials and Methods: The study was carried out on 100 patients scheduled for lower limb surgeries and were randomly divided into two groups of 50 each. In Group A, patients received 20 ml of 0.5% ropivacaine for femoral nerve block and same dose for sciatic nerve block and in Group B, 25 μg fentanyl was added each for femoral nerve and sciatic nerve block along with ropivacaine. All hemodynamic parameters, onset and duration of sensory and motor blocks were noted. The patient characteristics were analyzed using the “Chi-square tests” and the intergroup comparison of the parametric data was carried out using the unpaired t-test using software IBM SPSS 17.0. Results: Combined femoral and sciatic nerve block provide longer duration of postoperative analgesia of about 12–13 h. All the above-mentioned parameters were statistically non-significant. Conclusion: Hence in this study, onset and duration of sensory and motor block was comparable in both groups. However postoperative analgesia was prolonged as compared to neuraxial blockade without any hemodynamic instability. PMID:27746528

  1. 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

  2. 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.

  3. Paraproteinemic neuropathy: a practical review.

    PubMed

    Rison, Richard A; Beydoun, Said R

    2016-01-01

    The term paraproteinemic neuropathy describes a heterogeneous set of neuropathies characterized by the presence of homogeneous immunoglobulin in the serum. An abnormal clonal proliferation of B-lymphocytes or plasma cells, which may or may not occur in the context of a hematologic malignancy, produces the immunoglobulins in excess. If malignancy is identified, treatment should be targeted to the neoplasm. Most cases, however, occur as monoclonal gammopathy of undetermined significance. Few prospective, randomized, placebo-controlled trials are available to inform the management of paraproteinemic neuropathies. Clinical experience combined with data from smaller, uncontrolled studies provide a basis for recommendations, which depend on the specific clinical setting in which the paraprotein occurs. In this review, we provide a clinically practical approach to diagnosis and management of such patients. PMID:26821540

  4. Generalized pruritus preceding paraneoplastic neuropathy.

    PubMed

    Hébant, Benjamin; Miret, Nicolas; Berthelot, Lucile; Jaafar, Mohamad; Maltête, David; Lefaucheur, Romain

    2016-04-01

    Paraneoplastic syndromes are a group of rare disorders involving non-metastatic systemic effects accompanying malignancies, and occur remotely from the tumor itself. Chronic pruritus lasting more than 6 weeks can be from paraneoplastic origin. A 65-year-old woman was admitted for generalized pruritus lasting for 1 month, despite treatment with prednisolone, levocetirizine and hydroxyzine. General examination was normal. Biological data and gastroscopy were normal. One month later, the patient was readmitted for worsening of her pruritus and walking impairment, revealing a severe sensory neuropathy. Blood anti-Hu antibodies returned positive at a level of 400 (normal <100). Bronchoscopy and bronchial biopsies revealed small-cell lung carcinoma. To our knowledge, the association of generalized pruritus and paraneoplastic neuropathy has been rarely reported. Our observation raises the question of a pathophysiological continuum between pruritus and neuropathy in a paraneoplastic context. PMID:26633089

  5. 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

  6. Entrapment neuropathies in diabetes mellitus.

    PubMed

    Rota, Eugenia; Morelli, Nicola

    2016-09-15

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

  7. Entrapment neuropathies in diabetes mellitus.

    PubMed

    Rota, Eugenia; Morelli, Nicola

    2016-09-15

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

  8. 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. PMID:26820076

  9. Peripheral neuropathy and antiretroviral drugs.

    PubMed

    Dalakas, M C

    2001-03-01

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

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

    PubMed

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

    2016-07-15

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

  11. Peripheral neuropathy caused by methaqualone.

    PubMed

    Marks, P; Sloggem, J

    1976-01-01

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

  12. Inflammation: therapeutic targets for diabetic neuropathy.

    PubMed

    Zhou, Jiyin; Zhou, Shiwen

    2014-02-01

    There are still no approved treatments for the prevention or of cure of diabetic neuropathy, and only symptomatic pain therapies of variable efficacy are available. Inflammation is a cardinal pathogenic mechanism of diabetic neuropathy. The relationships between inflammation and the development of diabetic neuropathy involve complex molecular networks and processes. Herein, we review the key inflammatory molecules (inflammatory cytokines, adhesion molecules, chemokines) and pathways (nuclear factor kappa B, JUN N-terminal kinase) implicated in the development and progression of diabetic neuropathy. Advances in the understanding of the roles of these key inflammatory molecules and pathways in diabetic neuropathy will facilitate the discovery of the potential of anti-inflammatory approaches for the inhibition of the development of neuropathy. Specifically, many anti-inflammatory drugs significantly inhibit the development of different aspects of diabetic neuropathy in animal models and clinical trials.

  13. Electrophysiological profile in arsenic neuropathy.

    PubMed

    Oh, S J

    1991-12-01

    Comprehensive electrophysiological studies were performed on 13 patients with arsenic neuropathy. The most prominent finding was a marked abnormality in sensory nerve conduction in the presence of moderate abnormalities in motor nerve conduction. The motor nerve conduction studies and needle EMG were typical of those seen in axonal degeneration which was confirmed by sural nerve biopsy.

  14. Phrenic neuropathy in arsenic poisoning.

    PubMed

    Bansal, S K; Haldar, N; Dhand, U K; Chopra, J S

    1991-09-01

    A patient presented with acute arsenic neuropathy with asymmetric bilateral phrenic nerve involvement. The clinical and roentgenographic observations of phrenic nerve dysfunction were confirmed by prolonged phrenic nerve conduction time. The patient made a significant recovery with d-penicillamine therapy.

  15. DNA testing in hereditary neuropathies.

    PubMed

    Murphy, Sinéad M; Laurá, Matilde; Reilly, Mary M

    2013-01-01

    The inherited neuropathies are a clinically and genetically heterogeneous group of disorders in which there have been rapid advances in the last two decades. Molecular genetic testing is now an integral part of the evaluation of patients with inherited neuropathies. In this chapter we describe the genes responsible for the primary inherited neuropathies. We briefly discuss the clinical phenotype of each of the known inherited neuropathy subgroups, describe algorithms for molecular genetic testing of affected patients and discuss genetic counseling. The basic principles of careful phenotyping, documenting an accurate family history, and testing the available genes in an appropriate manner should identify the vast majority of individuals with CMT1 and many of those with CMT2. In this chapter we also describe the current methods of genetic testing. As advances are made in molecular genetic technologies and improvements are made in bioinformatics, it is likely that the current time-consuming methods of DNA sequencing will give way to quicker and more efficient high-throughput methods, which are briefly discussed here.

  16. 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.

  17. Ameliorative effects of amiloride and pralidoxime in chronic constriction injury and vincristine induced painful neuropathy in rats.

    PubMed

    Muthuraman, Arunachalam; Jaggi, Amteshwar Singh; Singh, Nirmal; Singh, Dhandeep

    2008-06-10

    The present study was designed to investigate the ameliorative effects of clinically available drugs, with Na+/Ca2+ and Na+/H+ exchange inhibitory actions, in chronic constriction injury and vincristine induced painful neuropathy in rats. Sciatic nerve ligation and vincristine treatment (50 microg/kg for 10 days) was employed to induce neuropathy in rats. Paw pressure, von Frey hair, acetone drop, and tail heat immersion tests were performed to assess degree of mechano-hyperalgesia, mechano-allodynia, cold chemical allodynia and spinal thermal sensation respectively. Axonal degeneration of sciatic nerve was assessed histopathologically. The levels of thio-barbituric acid reactive species, reduced glutathione, and total calcium were determined to assess biochemical alterations. Amiloride (15 mg/kg i.p.), Na+/Ca2+ and Na+/H+ exchange inhibitor, and pralidoxime (20 mg/kg i.p.), Na+/Ca2+ exchange inhibitor, were administered for 10 consecutive days starting from the day of surgery or vincristine administration. Sciatic nerve ligation and vincristine treatment resulted in significant axonal degeneration, development of mechano-hyperalgesia, mechano-allodynia, cold chemical allodynia and spinal heat hyperalgesia and also resulted in rise in thio-barbituric acid reactive species, total calcium and decrease in reduced glutathione levels. Administration of amiloride and pralidoxime attenuated chronic constriction injury and vincristine induced axonal degeneration and reduction of nociceptive threshold along with reduction in calcium levels and oxidative stress. The observed anti-nociceptive effects of amiloride and pralidoxime may possibly be attributed to inhibition of Na+/Ca2+ and Na+/H+ exchangers with subsequent decrease in Ca2+ ions and oxidative stress. PMID:18486127

  18. Hereditary sensory neuropathy type I

    PubMed Central

    Auer-Grumbach, Michaela

    2008-01-01

    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

  19. Hereditary sensory neuropathy type I.

    PubMed

    Auer-Grumbach, Michaela

    2008-01-01

    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

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

    PubMed Central

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

    2015-01-01

    Background Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells. Methods Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves. Results Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12) cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice. Conclusion These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes. PMID:26536615

  1. Entrapment Neuropathies in the Upper and Lower Limbs: Anatomy and MRI Features

    PubMed Central

    Dong, Qian; Jacobson, Jon A.; Jamadar, David A.; Gandikota, Girish; Brandon, Catherine; Morag, Yoav; Fessell, David P.; Kim, Sung-Moon

    2012-01-01

    Peripheral nerve entrapment occurs at specific anatomic locations. Familiarity with the anatomy and the magnetic resonance imaging (MRI) features of nerve entrapment syndromes is important for accurate diagnosis and early treatment of entrapment neuropathies. The purpose of this paper is to illustrate the normal anatomy of peripheral nerves in the upper and lower limbs and to review the MRI features of common disorders affecting the peripheral nerves, both compressive/entrapment and noncompressive, involving the suprascapular nerve, the axillary nerve, the radial nerve, the ulnar nerve, and the median verve in the upper limb and the sciatic nerve, the common peroneal nerve, the tibial nerve, and the interdigital nerves in the lower limb. PMID:23125929

  2. Early onset (childhood) monogenic neuropathies.

    PubMed

    Landrieu, Pierre; Baets, Jonathan

    2013-01-01

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

  3. Jinmaitong decreases sciatic nerve DNA oxidative damage and apoptosis in a streptozotocin-induced diabetic rat model

    PubMed Central

    YIN, DE-HAI; LIANG, XIAO-CHUN; ZHAO, LI; ZHANG, HONG; SUN, QING; WANG, PU-YAN; SUN, LIAN-QING

    2015-01-01

    Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes. Jinmaitong (JMT), a Traditional Chinese Medicine, improves certain symptoms of DPN, such as limb pain and numbness. The aim of the present study was to investigate the effects of JMT on DNA oxidative damage and apoptosis in the sciatic nerve of diabetic rats. The rats were divided into a normal and a diabetic group. Diabetes was induced using streptozotocin (60 mg/kg). The diabetic model (DM) rats received vitamin C (0.05 g/kg/day) or JMT [low-dosage (L), 0.44 g/kg/day; medium-dosage (M), 0.88 g/kg/day or high-dosage (H), 1.75 g/kg/day]. After 16 weeks, the mechanical pain threshold of the rats was evaluated. The expression of 8-hydroxy-deoxyguanosine (8-OHdG), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox, B-cell lymphoma 2 (Bcl-2), caspase 3 and cleaved-poly(ADP-ribose) polymerase 1 (PARP-1) in the sciatic nerve tissues was measured using the reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blotting. JMT had no effect on body weight and fasting blood glucose levels. Following treatment, the rats in the JMT groups had an improved pain threshold compared with the DM controls (JMT-L, 52.9±6.5 g; JMT-M, 74.7±9.3 g; and JMT-H, 61.7±2.0 g vs. DM control, 35.32±12.06 g; all P<0.01), while the threshold in the JMT-M rats was similar to that of normal controls (P>0.05). 8-OHdG and NADPH oxidase p22phox expression was significantly decreased in the three JMT groups compared with that in the DM controls (all P<0.05). Following JMT treatment, Bcl-2 levels were increased, while caspase 3 and cleaved-PARP-1 levels were decreased compared with those in the DM controls (all P<0.01). In conclusion, JMT may reduce DNA oxidative damage to the sciatic nerve in diabetic rats, as well as regulate genes involved in peripheral neuronal cell apoptosis, suggesting that JMT could be used to prevent or treat DPN in diabetic patients. PMID

  4. 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.

  5. Efficacy of nanofibrous conduits in repair of long-segment sciatic nerve defects

    PubMed Central

    Biazar, Esmaeil; Keshel, Saeed Heidari; Pouya, Majid

    2013-01-01

    Our previous studies have histomorphologically confirmed that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on rat behaviors remain poorly understood. In this study, we used nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) conduit and autologous sciatic nerve to bridge 30-mm-long rat sciatic nerve gaps. Within 4 months after surgery, rat sciatic nerve functional recovery was evaluated per month by behavioral analyses, including toe out angle, toe spread analysis, walking track analysis, extensor postural thrust, swimming test, open-field analysis and nociceptive function. Results showed that rat sciatic nerve functional recovery was similar after nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) conduit and autologous nerve grafting. These findings suggest that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) conduit is suitable in use for repair of long-segment sciatic nerve defects. PMID:25206560

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2012-08-01

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

  8. Is the Sciatic Functional Index always reliable and reproducible?

    PubMed

    Monte-Raso, Vanessa Vilela; Barbieri, Cláudio Henrique; Mazzer, Nilton; Yamasita, Alexandre Calura; Barbieri, Giuliano

    2008-05-30

    The Sciatic Functional Index (SFI) is a quite useful tool for the evaluation of functional recovery of the sciatic nerve of rats in a number of experimental injuries and treatments. Although it is an objective method, it depends on the examiner's ability to adequately recognize and mark the previously established footprint key points, which is an entirely subjective step, thus potentially interfering with the calculations according to the mathematical formulae proposed by different authors. Thus, an interpersonal evaluation of the reproducibility of an SFI computer-aided method was carried out here to study data variability. A severe crush injury was produced on a 5 mm-long segment of the right sciatic nerve of 20 Wistar rats (a 5000 g load directly applied for 10 min) and the SFI was measured by four different examiners (an experienced one and three newcomers) preoperatively and at weekly intervals from the 1st to the 8th postoperative week. Three measurements were made for each print and the average was calculated and used for statistical analysis. The results showed that interpersonal correlation was high (0.82) in the 3rd, 4th, 5th, 7th and 8th weeks, with an unexpected but significant (p<0.01) drop in the 6th week. There was virtually no interpersonal correlation (correlation index close to 0) on the 1st and 2nd weeks, a period during which the variability between animals and examiners (p=0.24 and 0.32, respectively) was similar, certainly due to a poor definition of the footprints. The authors conclude that the SFI method studied here is only reliable from the 3rd week on after a severe lesion of the sciatic nerve of rats.

  9. 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

  10. Immune cell distribution and immunoglobulin levels change following sciatic nerve injury in a rat model

    PubMed Central

    Yuan, Wei; Feng, Xinhong

    2016-01-01

    Objective(s): To investigate the systemic and local immune status of two surgical rat models of sciatic nerve injury, a crushed sciatic nerve, and a sciatic nerve transection Materials and Methods: Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group), sciatic nerve crush, and sciatic nerve transaction. Sciatic nerve surgery was performed. The percentage of CD4+ cells and the CD4+/CD8+ratio were determined by flow cytometry. Serum IgM and IgG levels were analyzed by ELISA. T-cells (CD3) and macrophages (CD68) in sciatic nerve tissue sections were identified through immunohistochemistry. Results: Compared to sham-operated controls, in rats that underwent nerve injury, the percentage of CD4+ cells and the CD4+/CD8+ ratio in the peripheral blood were significantly decreased 7 days after surgery, serum IgM levels were increased 14 days after surgery, and serum IgG levels were increased 21 days after surgery. There were a large number of CD3+ cells and a small number of CD68+ cells in sciatic nerve tissue sections 21 days after surgery, indicating T-cell and macrophage activation and infiltration. Local IgG deposition was also detected at the nerve injury site 21 days after surgery. Conclusion: Rat humoral and cellular immune status changed following sciatic nerve injury, particularly with regard to the cellular immune response at the nerve injury site.

  11. 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.

  12. Immune cell distribution and immunoglobulin levels change following sciatic nerve injury in a rat model

    PubMed Central

    Yuan, Wei; Feng, Xinhong

    2016-01-01

    Objective(s): To investigate the systemic and local immune status of two surgical rat models of sciatic nerve injury, a crushed sciatic nerve, and a sciatic nerve transection Materials and Methods: Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group), sciatic nerve crush, and sciatic nerve transaction. Sciatic nerve surgery was performed. The percentage of CD4+ cells and the CD4+/CD8+ratio were determined by flow cytometry. Serum IgM and IgG levels were analyzed by ELISA. T-cells (CD3) and macrophages (CD68) in sciatic nerve tissue sections were identified through immunohistochemistry. Results: Compared to sham-operated controls, in rats that underwent nerve injury, the percentage of CD4+ cells and the CD4+/CD8+ ratio in the peripheral blood were significantly decreased 7 days after surgery, serum IgM levels were increased 14 days after surgery, and serum IgG levels were increased 21 days after surgery. There were a large number of CD3+ cells and a small number of CD68+ cells in sciatic nerve tissue sections 21 days after surgery, indicating T-cell and macrophage activation and infiltration. Local IgG deposition was also detected at the nerve injury site 21 days after surgery. Conclusion: Rat humoral and cellular immune status changed following sciatic nerve injury, particularly with regard to the cellular immune response at the nerve injury site. PMID:27635205

  13. Genetics Home Reference: hereditary neuropathy with liability to pressure palsies

    MedlinePlus

    ... hereditary neuropathy with liability to pressure palsies hereditary neuropathy with liability to pressure palsies Enable Javascript to ... Download PDF Open All Close All Description Hereditary neuropathy with liability to pressure palsies is a disorder ...

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

    MedlinePlus

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

  15. Genetics Home Reference: distal hereditary motor neuropathy, type V

    MedlinePlus

    ... hereditary motor neuropathy, type V distal hereditary motor neuropathy, type V Enable Javascript to view the expand/ ... Open All Close All Description Distal hereditary motor neuropathy, type V is a progressive disorder that affects ...

  16. Genetics Home Reference: hereditary sensory neuropathy type IA

    MedlinePlus

    ... Conditions hereditary sensory neuropathy type IA hereditary sensory neuropathy type IA Enable Javascript to view the expand/ ... PDF Open All Close All Description Hereditary sensory neuropathy type IA is a condition characterized by nerve ...

  17. Neuromuscular ultrasound in common entrapment neuropathies.

    PubMed

    Cartwright, Michael S; Walker, Francis O

    2013-11-01

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

  18. Peripheral neuropathy in arsenic smelter workers.

    PubMed

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

    1979-07-01

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

  19. Axonal loss and neuroprotection in optic neuropathies.

    PubMed

    Levin, Leonard A

    2007-06-01

    Most optic neuropathies do not have effective treatments. Examples are ischemic optic neuropathy, Leber hereditary optic neuropathy, optic neuritis, and traumatic optic neuropathy. In some cases, the pathophysiology of the optic nerve injury is not fully understood. For example, while the demyelinative aspects of optic neuritis have been studied, the mechanism by which the axonal loss occurs is less apparent. In other cases, although the pathophysiology of the optic neuropathy may be understood, there is difficulty treating the disease, for example, with traumatic optic neuropathy. In response to this therapeutic dearth, the concept of neuroprotection has arisen. Neuroprotection is a therapeutic paradigm for preventing death of neurons from injury and maintaining function. In optic neuropathies, the corresponding neuron is the retinal ganglion cell. These cells are unable to divide, and optic neuropathies irrevocably result in their death; therefore, the primary target of neuroprotection are retinal ganglion cells and their axons. This review emphasizes that most optic neuropathies are axonal and thus good targets for neuroprotection. PMID:17508035

  20. Amelioration by the Ca2+ antagonist, nimodipine of an existing neuropathy in the streptozotocin-induced, diabetic rat.

    PubMed Central

    Kappelle, A. C.; Bravenboer, B.; van Buren, T.; Traber, J.; Erkelens, D. W.; Gispen, W. H.

    1993-01-01

    1. Neuropathy is a frequently diagnosed complication in diabetic patients but an effective treatment does not exist. 2. The development of neuropathy in streptozotocin-induced diabetic rats was monitored by measuring the motor and sensory nerve conduction velocity in the sciatic nerve. 3. A significant decrease in sensory and motor nerve conduction velocity was apparent in young, 14-week-old diabetic rats as compared to non-diabetic, age-matched controls 4 weeks after the induction of diabetes with streptozotocin. 4. Intraperitoneal treatment with the Ca2+ channel blocker, nimodipine, from week 4 onwards, in a dosage of 10 mg kg-1 or 20 mg kg-1 intraperitoneally per 48 h, resulted in a significant increase in sensory and motor nerve conduction velocity whereas treatment with 5 mg kg-1 intraperitoneally per 48 h was not effective. 5. One-year-old, adult, diabetic rats treated with nimodipine 20 mg kg-1 (treatment started again 4 weeks after induction of diabetes mellitus) also showed an increase of both sensory and motor nerve conduction velocity as compared to diabetic rats treated with placebo. 6. It is concluded that nimodipine ameliorates existing experimental diabetic neuropathy in streptozotocin-induced diabetic rats in both young and adult animals. PMID:8467365

  1. 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.

  2. [Method of studying the microcirculation of the sciatic nerve during life].

    PubMed

    Razumova, I L; Chernukh, A M

    1977-02-01

    The authors describe a mehtod of bloodless exposure of the sciatic nerve in rats, of placing it on the light conductor, and of the preparation of microscope MBI-6 for the intravital study of microhemocirculation in the epineurium of the sciatic nerve. Different types of the microvessel network of rat are demonstrated.

  3. Diabetic Neuropathy: One disease or two?

    PubMed Central

    Callaghan, Brian C.; Hur, Junguk; Feldman, Eva L.

    2014-01-01

    Purpose of review To compare and contrast the evidence for the effect of glucose control on the prevention of neuropathy in type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. Recent findings In T1DM, multiple clinical trials have demonstrated a large benefit from enhanced glucose control, whereas the benefit in T2DM is much more modest. Epidemiologic and laboratory evidence exists to support factors other than hyperglycemia in the development of neuropathy including obesity, hypertension, dyslipidemia, inflammation, and insulin resistance. Summary T1DM neuropathy and T2DM neuropathy are fundamentally different. In T1DM, glucose control has a large effect on the prevention of neuropathy; therefore future efforts should continue to concentrate on this avenue of treatment. In contrast, in T2DM, glucose control has a small effect on the prevention of neuropathy; as a result, more research is needed to define the underlying mechanisms for the development of neuropathy. Understanding these mechanisms may lead to novel therapeutic approaches to prevent or treat diabetic neuropathy. PMID:22892951

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. N-hexane neuropathy in offset printers.

    PubMed Central

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

    1993-01-01

    In an offset printing factory with 56 workers, 20 (36%) developed symptomatic peripheral neuropathy due to exposure to n-hexane. Another 26 workers (46%) were found to have subclinical neuropathy. The initial change in the nerve conduction study was reduced amplitude of the sensory action potentials, followed by reduced amplitude of the motor action potentials, reduction in motor conduction velocities and increase in distal latencies. These changes indicate primary axonal degeneration with secondary demyelination. Sural nerve biopsy in a severe case showed giant axonal swellings due to accumulation of 10nm neurofilaments, myelin sheath attenuation and widening of nodal gaps. The development of neuropathy bore no direct relationship to the duration of exposure, hence factors such as individual susceptibility may be important. Optic neuropathy and CNS involvement were uncommon and autonomic neuropathy was not encountered. Images PMID:8505647

  9. Animal models of HIV peripheral neuropathy

    PubMed Central

    Burdo, Tricia H; Miller, Andrew D

    2014-01-01

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

  10. Suprascapular neuropathy in volleyball players

    PubMed Central

    Witvrouw, E; Cools, A; Lysens, R; Cambier, D; Vanderstraeten, G; Victor, J; Sneyers, C; Walravens, M

    2000-01-01

    Background—Suprascapular nerve entrapment with isolated paralysis of the infraspinatus muscle is uncommon. However, this pathology has been reported in volleyball players. Despite a lack of scientific evidence, excessive strain on the nerve is often cited as a possible cause of this syndrome. Previous research has shown a close association between shoulder range of motion and strain on the suprascapular nerve. No clinical studies have so far been designed to examine the association between excessive shoulder mobility and the presence of this pathology. Aim—To study the possible association between the range of motion of the shoulder joint and the presence of suprascapular neuropathy by clinically examining the Belgian male volleyball team with respect to several parameters. Methods—An electromyographic investigation, a clinical shoulder examination, shoulder range of motion measurements, and an isokinetic concentric peak torque shoulder internal/external rotation strength test were performed in 16 professional players. Results—The electrodiagnostic study showed a severe suprascapular neuropathy in four players which affected only the infraspinatus muscle. In each of these four players, suprascapular nerve entrapment was present on the dominant side. Except for the hypotrophy of the infraspinatus muscle, no significant differences between the affected and non-affected players were observed on clinical examination. Significant differences between the affected and non-affected players were found for range of motion measurements of external rotation, horizontal flexion and forward flexion, and for flexion of the shoulder girdle (protraction); all were found to be higher in the affected players than the non-affected players. Conclusions—This study suggests an association between increased range of motion of the shoulder joint and the presence of isolated paralysis of the infraspinatus muscle in volleyball players. However, the small number of patients in this

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

    PubMed Central

    Ceranic, B; Luxon, L

    2004-01-01

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

  12. Effects of Long-Term Treatment with Ranirestat, a Potent Aldose Reductase Inhibitor, on Diabetic Cataract and Neuropathy in Spontaneously Diabetic Torii Rats

    PubMed Central

    Ota, Ayumi; Kakehashi, Akihiro; Toyoda, Fumihiko; Kinoshita, Nozomi; Shinmura, Machiko; Takano, Hiroko; Obata, Hiroto; Matsumoto, Takafumi; Tsuji, Junichi; Dobashi, Yoh; Fujimoto, Wilfred Y.; Kawakami, Masanobu; Kanazawa, Yasunori

    2013-01-01

    We evaluated ranirestat, an aldose reductase inhibitor, in diabetic cataract and neuropathy (DN) in spontaneously diabetic Torii (SDT) rats compared with epalrestat, the positive control. Animals were divided into groups and treated once daily with oral ranirestat (0.1, 1.0, 10 mg/kg) or epalrestat (100 mg/kg) for 40 weeks, normal Sprague-Dawley rats, and untreated SDT rats. Lens opacification was scored from 0 (normal) to 3 (mature cataract). The combined scores (0–6) from both lenses represented the total for each animal. DN was assessed by measuring the motor nerve conduction velocity (MNCV) in the sciatic nerve. Sorbitol and fructose levels were measured in the lens and sciatic nerve 40 weeks after diabetes onset. Cataracts developed more in untreated rats than normal rats (P < 0.01). Ranirestat significantly (P < 0.01) inhibited rapid cataract development; epalrestat did not. Ranirestat significantly reversed the MNCV decrease (40.7 ± 0.6 m/s) in SDT rats dose-dependently (P < 0.01). Epalrestat also reversed the prevented MNCV decrease (P < 0.05). Sorbitol levels in the sciatic nerve increased significantly in SDT rats (2.05 ± 0.10 nmol/g), which ranirestat significantly suppressed dose-dependently, (P < 0.05, <0.01, and <0.01); epalrestat did not. Ranirestat prevents DN and cataract; epalrestat prevents DN only. PMID:23671855

  13. 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.

  14. Sciatic nerve repair using adhesive bonding and a modified conduit

    PubMed Central

    Liang, Xiangdang; Cai, Hongfei; Hao, Yongyu; Sun, Geng; Song, Yaoyao; Chen, Wen

    2014-01-01

    When repairing nerves with adhesives, most researchers place glue directly on the nerve stumps, but this method does not fix the nerve ends well and allows glue to easily invade the nerve ends. In this study, we established a rat model of completely transected sciatic nerve injury and repaired it using a modified 1 cm-length conduit with inner diameter of 1.5 mm. Each end of the cylindrical conduit contains a short linear channel, while the enclosed central tube protects the nerve ends well. Nerves were repaired with 2-octyl-cyanoacrylate and suture, which complement the function of the modified conduit. The results demonstrated that for the same conduit, the average operation time using the adhesive method was much shorter than with the suture method. No significant differences were found between the two groups in sciatic function index, motor evoked potential latency, motor evoked potential amplitude, muscular recovery rate, number of medullated nerve fibers, axon diameter, or medullary sheath thickness. Thus, the adhesive method for repairing nerves using a modified conduit is feasible and effective, and reduces the operation time while providing an equivalent repair effect. PMID:25206861

  15. Autonomic Neuropathy in Diabetes Mellitus

    PubMed Central

    Verrotti, Alberto; Prezioso, Giovanni; Scattoni, Raffaella; Chiarelli, Francesco

    2014-01-01

    Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. The pathogenesis is still unclear and probably multifactorial. Once DAN becomes clinically evident, no form of therapy has been identified, which can effectively stop or reverse it. Prevention strategies are based on strict glycemic control with intensive insulin treatment, multifactorial intervention, and lifestyle modification including control of hypertension, dyslipidemia, stop smoking, weight loss, and adequate physical exercise. The present review summarizes the latest knowledge regarding clinical presentation, epidemiology, pathogenesis, and management of DAN, with some mention to childhood and adolescent population. PMID:25520703

  16. Peroneal neuropathy after weight loss.

    PubMed

    Cruz-Martinez, A; Arpa, J; Palau, F

    2000-06-01

    The objectives of this study were to evaluate the clinical and electrophysiological findings in peroneal mononeuropathies following a weight-reduction diet. Thirty patients with acute peroneal palsy and weight loss were studied. Complete nerve conduction studies (NCS) were performed in upper and lower limbs. NCS showed conduction block (CB) of the peroneal nerve at the fibular head that recovered in 29 patients within 3 weeks to 3 months. Severity of CB was correlated with clinical weakness. Three patients had abnormalities consistent with polyneuropathy (PNP). NCS in asymptomatic relatives confirmed familial neuropathy. Nerve biopsy and molecular study were consistent with hereditary neuropathy with liability to pressure palsies (HNPP). One of these peroneal palsies (6 months) recovered after neurolysis. Weight loss might be a risk factor in peroneal mononeuropathies. NCS is a tool in the diagnosis of the site and severity of the nerve injury. Testing should be considered for relatives of patients with PNP because peroneal mononeuropathies may be the first expression of HNPP.

  17. Drugs for the treatment of peripheral neuropathies.

    PubMed

    Marmiroli, Paola; Cavaletti, Guido

    2016-01-01

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

  18. Optic neuropathy associated with systemic sarcoidosis

    PubMed Central

    Burton, Ben J.; Graham, Elizabeth M.; Plant, Gordon T.

    2016-01-01

    Objective: To identify and follow a series of 52 patients with optic neuropathy related to sarcoidosis. Methods: Prospective observational cohort study. Results: The disorder was more common in women and affected a wide age range. It was proportionately more common in African and Caribbean ethnic groups. Two clinical subtypes were identified: the more common was a subacute optic neuropathy resembling optic neuritis; a more slowly progressive optic neuropathy arose in the remaining 17%. Sixteen (31%) were bilateral. Concurrent intraocular inflammation was seen in 36%. Pain arose in only 27% of cases. An optic perineuritis was seen in 2 cases, and predominate involvement of the chiasm in one. MRI findings showed optic nerve involvement in 75% of cases, with adjacent and more widespread inflammation in 31%. Treatment with corticosteroids was helpful in those with an inflammatory optic neuropathy, but not those with mass lesions. Relapse of visual signs arose in 25% of cases, necessitating an increase or escalation of treatment, but relapse was not a poor prognostic factor. Conclusions: This is a large prospective study of the clinical characteristics and outcome of treatment in optic neuropathy associated with sarcoidosis. Patients who experience an inflammatory optic neuropathy respond to treatment but may relapse. Those with infiltrative or progressive optic neuropathies improve less well even though the inflammatory disorder responds to therapy. PMID:27536707

  19. Drugs for the treatment of peripheral neuropathies.

    PubMed

    Marmiroli, Paola; Cavaletti, Guido

    2016-01-01

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

  20. Diabetic neuropathy in db/db mice develops independently of changes in ATPase and aldose reductase. A biochemical and immunohistochemical study.

    PubMed

    Bianchi, R; Marelli, C; Marini, P; Fabris, M; Triban, C; Fiori, M G

    1990-03-01

    ATPase activity was investigated in sciatic and optic nerves of female mutant diabetic C57Bl/Ks (db/db) mice and age-matched control mice (db/m and m/m). Nerves from animals aged 50, 70, 125, 180 and 280 days were assayed in vitro for ATPase activity in the presence or absence of ouabain: the ouabain-sensitive fraction contained Na+,K(+)-ATPase. Enzymatic activity was compared within and between age-matched groups. No significant difference in Na+,K(+)-ATPase activity was detected between the diabetic and control mice, whether expressed as mumol Pi/h-1 formed per gramme wet weight or per nerve (protein content). The activity decreased by about 25% in both the sciatic and optic nerves of the oldest animals. These results were strikingly similar in all groups, regardless of the type of nerve examined, confirming that the development of neuropathy in this animal model is unrelated to the postulated derangement of Na+,K(+)-ATPase activity. Among possible explanations, a lack of polyol pathway activation was investigated by staining the sciatic nerves of animals from all groups with the peroxidase-antiperoxidase procedure using a polyclonal antiserum raised against the enzyme aldose reductase. Histological sections of all nerves were consistently negative, suggesting that these animals actually lack the enzyme involved in activating the self-perpetuating metabolic cycle leading to deranged nerve function. The db/db mouse appears to present particular biochemical changes which merit attention with a view to clarifying the pathogenesis of diabetic neuropathy.

  1. Anti-neurofilament antibodies in neuropathy with monoclonal gammopathy of undetermined significance produce experimental motor nerve conduction block.

    PubMed

    Stubbs, Evan B; Lawlor, Mike W; Richards, Michael P; Siddiqui, Kiran; Fisher, Morris A; Bhoopalam, Nirmala; Siegel, George J

    2003-02-01

    Elevated levels of serum antibodies to neurofilament proteins have been associated with a variety of neurological diseases, including autoimmune disorders such as neuropathy with monoclonal gammopathy of undetermined significance (MGUS). The pathological significance of anti-neurofilament antibodies in sera of affected patients, however, remains unclear. In this study, we report our findings of polyclonal antibodies in sera from 4 of 16 IgG MGUS neuropathy patients that react strongly on immunoblot with a high molecular weight neurofilament protein (NFH). The effect of anti-NFH polyclonal antibody on peripheral nerve function was tested in vivo by intraneural injection. Sera containing anti-NFH antibody, but not sera from age-matched control subjects, injected into the endoneurium of rat sciatic nerve significantly attenuated proximal-evoked motor nerve compound muscle action potential (CMAP) amplitudes in a complement-dependent manner. In contrast, ankle-evoked CMAP amplitudes were unaffected by intraneural injection of sera containing anti-NFH antibody. Anti-NFH serum-injected nerves showed changes in both axon caliber (shrinkage) and myelin ultrastructure (vesiculation and ovoid formation), suggestive of intramyelinic edema. Preincubation of sera containing anti-NFH antibody with purified NFH protein abolished immunoreactivity to NFH protein and neutralized the serum-mediated toxicity. The data suggest that anti-NFH polyclonal antibodies occurring in sera of some patients with IgG MGUS neuropathy may elicit peripheral nerve conduction block independent of the patients' IgG paraprotein. Anti-neural polyclonal antibodies in sera of IgG MGUS neuropathy patients may have a greater pathological significance than previously anticipated.

  2. Electrodiagnostic testing in diabetic neuropathy: Which limb?

    PubMed

    Rota, E; Cocito, D

    2015-10-01

    Electrodiagnosis of subclinical diabetic neuropathies by nerve conduction studies remains challenging. The question arises about which nerves should be tested and what the best electrodiagnostic protocol to make an early diagnosis of diabetic neuropathies would be. On the basis of our findings and other evidence, which highlighted the remarkable prevalence of electrophysiological abnormalities in nerve conduction studies of the upper limbs, often in the presence of normal lower limb conduction parameters, we suggest that both ulnar and median nerves, in their motor and sensitive component, should be the two target nerves for electrodiagnostic protocols in diabetic neuropathies.

  3. Novel MPZ mutations and congenital hypomyelinating neuropathy

    PubMed Central

    McMillan, Hugh J.; Santagata, Sandro; Shapiro, Frederic; Batish, Sat Dev; Couchon, Libby; Donnelly, Stephen; Kang, Peter B.

    2010-01-01

    We report two new MPZ mutations causing congenital hypomyelinating neuropathies; c.368_382delGCACGTTCACTTGTG (in-frame deletion of five amino acids) and c.392A>G, Asn131Ser. Each child had clinical and electrodiagnostic features consistent with an inherited neuropathy, confirmed by sural nerve biopsy. The cases illustrate the clinically heterogeneity that exists even within early-onset forms of this disease. They also lend additional support to the emerging clinical and laboratory evidence that impaired intracellular protein trafficking may represent the cause of some congenital hypomyelinating neuropathies. PMID:20621479

  4. 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.

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

    PubMed

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

    2003-07-01

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

  6. The neuropathy of erectile dysfunction.

    PubMed

    Bleustein, C B; Arezzo, J C; Eckholdt, H; Melman, A

    2002-12-01

    These studies were intended to explore the relationship between autonomic neuropathy and erectile dysfunction (ED). Sensory thresholds reflecting the integrity of both large diameter, myelinated neurons (ie pressure, touch, vibration) and small diameter axons (ie hot and cold thermal sensation) were determined on the penis and finger. Data were compared across subjects with and without ED, controlling for age, hypertension and diabetes. The correlation of specific thresholds scores and IIEF values were also examined. Seventy-three patients who visited the academic urology clinics at Montefiore hospital were evaluated. All patients were required to complete the erectile function domain of the International Index of Erectile Function (IIEF) questionnaire: 20 subjects had no complaints of ED and scored within the 'normal' range on the IIEF. Patients were subsequently tested on their index finger and glans penis for vibration (Biothesiometer), pressure (Semmes-Weinstein monofilaments), spatial perception (Tactile Circumferential Discriminator), and warm and cold thermal thresholds (Physitemp NTE-2). Sensation of the glans penis, as defined by the examined sensory thresholds, was significantly diminished in patients with ED and these differences remained significant when controlling for age, diabetes and hypertension. In contrast, thresholds on the index finger were equivalent in the ED and non-ED groups. Threshold and IIEF scores were highly correlated, consistent with an association between diminished sensation and decreasing IIEF score (worse erectile functioning). These relations also remained significant when controlling for age, diabetes and hypertension. The findings demonstrate dysfunction of large and small diameter nerve fibers in patients with ED of all etiologies. Further, the neurophysiologic measures validate the use of the IIEF as an index of ED, as objective findings of sensory neuropathy were highly correlated with worse IIEF scores. The sensory

  7. Peripheral Neuropathy in Mouse Models of Diabetes.

    PubMed

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

    2016-01-01

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

  8. 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

  9. Vitamin B supplementation for diabetic peripheral neuropathy.

    PubMed

    Jayabalan, Bhavani; Low, Lian Leng

    2016-02-01

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

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

    PubMed

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

    1998-01-01

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

  11. Multiple cranial neuropathies following etanercept administration.

    PubMed

    Hunter, Jacob B; Rivas, Alejandro

    2016-01-01

    There have been recent reports of sarcoid-like granulomatosis development following the administration of tumor necrosis factor (TNF) inhibitors. To date, only four cases of neurosarcoidosis have been reported in association with TNF inhibitors, two of which were attributed to etanercept. We present the first case of etanercept-induced neurosarcoidosis involving multiple cranial neuropathies, including the trigeminal, facial, and vestibulocochlear nerves, while also highlighting the differential diagnoses of multiple cranial neuropathies and the association of TNF inhibitors and neurosarcoidosis. PMID:27178520

  12. 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

  13. 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.

  14. Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies.

    PubMed

    Lopez Sanchez, M I G; Crowston, J G; Mackey, D A; Trounce, I A

    2016-09-01

    Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated. Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function. PMID:27288727

  15. 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. PMID:27656390

  16. 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.

  17. [Composite resection of sciatic nerve for local recurrence of rectal cancer].

    PubMed

    Kameyama, M; Nakamori, S; Imaoka, S; Hinakawa, M; Sasaki, Y; Ishikawa, O; Kabuto, T; Furukawa, H; Iwanaga, T; Ueda, T

    1993-08-01

    Three patients with local recurrence of rectal cancer involving the sciatic nerve underwent radical pelvic exenteration combined with sciatic nerve resection. This surgical procedure resulted in complete relief of intolerable cancer pain in all patients. After the rehabilitation, all could walk unassisted by wearing only a below-the-knee leg brace. The first patient died 16 months postoperatively due to multiple liver metastasis, but no local recurrence was documented. The second patient is alive 13 months postoperatively with bone and liver metastasis and pelvic wall recurrence. The third patient is alive 7 months postoperatively with no evidence of disease. Composite resection of lateral sciatic nerve improved the quality of life in patients who had local recurrence of rectal cancer with sciatic nerve involvement.

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

    PubMed

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

    2013-05-01

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

  19. 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.

  20. Mouse Models of Diabetic Neuropathy

    PubMed Central

    Sullivan, Kelli A.; Hayes, John M.; Wiggin, Timothy D.; Backus, Carey; Oh, Sang Su; Lentz, Stephen I.; Brosius, Frank; Feldman, Eva L.

    2007-01-01

    Diabetic neuropathy (DN) is a debilitating complication of type 1 and type 2 diabetes. Rodent models of DN do not fully replicate the pathology observed in human patients. We examined DN in streptozotocin (STZ)-induced [B6] and spontaneous type 1 diabetes [B6Ins2Akita] and spontaneous type 2 diabetes [B6-db/db, BKS-db/db]. DN was defined using the criteria of the Animal Models of Diabetic Complications Consortium (http://www.amdcc.org). Despite persistent hyperglycemia, the STZ-treated B6 and B6Ins2Akita mice were resistant to the development of DN. In contrast, DN developed in both type 2 diabetes models: the B6-db/db and BKS-db/db mice. The persistence of hyperglycemia and development of DN in the B6-db/db mice required an increased fat diet while the BKS-db/db mice developed severe DN and remained hyperglycemic on standard mouse chow. Our data support the hypothesis that genetic background and diet influence the development of DN and should be considered when developing new models of DN. PMID:17804249

  1. Mouse Models of Diabetic Neuropathy

    PubMed Central

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

    2014-01-01

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

  2. Suprascapular neuropathy in volleyball players.

    PubMed

    Dramis, Asterios; Pimpalnerkar, Ashvin

    2005-06-01

    Entrapment neuropathy of the suprascapular nerve (SNE), although a recognised clinical entity, is a relatively rare cause of shoulder pain and subjective weakness in the athlete involved in overhead sports like volleyball and badminton. This study deals with the presentation and management of four unusual cases of suprascapular nerve entrapment in volleyball players. Four male volleyball players presented to our department with intractable shoulder pain and subjective sensation of shoulder weakness. They all had visible wasting of both supraspinatus and infraspinatus muscles, together with weakness of abduction and external rotation of the arm. They all responded temporarily to a diagnostic injection of local anaesthetic. MR imaging was useful in diagnosing space occupying lesions in three cases and the presence of a hypertrophic suprascapular ligament in one case. Due to failure of non- operative treatment, which included activity modification, rest, analgesics and rehabilitation programme over 6 months, surgery was then required to decompress the suprascapular nerve. All patients were symptom free at 6 months postoperatively and after an intensive rehabilitation programme, they were able to return to their normal level of activity including sport.

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

    PubMed

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

    2016-01-01

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

  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. Axonal pathology precedes demyelination in a mouse model of X-linked demyelinating/type I Charcot-Marie Tooth neuropathy.

    PubMed

    Vavlitou, Natalie; Sargiannidou, Irene; Markoullis, Kyriaki; Kyriacou, Kyriacos; Scherer, Steven S; Kleopa, Kleopas A

    2010-09-01

    The X-linked demyelinating/type I Charcot-Marie-Tooth neuropathy (CMT1X) is an inherited peripheral neuropathy caused by mutations in GJB1, the gene that encodes the gap junction protein connexin32. Connexin32 is expressed by myelinating Schwann cells and forms gap junctions in noncompact myelin areas, but axonal involvement is more prominent in X-linked compared with other forms of demyelinating Charcot-Marie-Tooth disease. To clarify the cellular and molecular mechanisms of axonal pathology in CMT1X, we studied Gjb1-null mice at early stages (i.e. 2-4 months old) of the neuropathy, when there is minimal or no demyelination. The diameters of large myelinated axons were progressively reduced in Gjb1-null mice compared with those in wild-type littermates. Furthermore, neurofilaments were relatively more dephosphorylated and more densely packed starting at 2 months of age. Increased expression of β-amyloid precursor protein, a marker of axonal damage, was also detected in Gjb1-null nerves. Finally, fast axonal transport, assayed by sciatic nerve ligation experiments, was slower in distal axons of Gjb1-null versus wild-type animals with reduced accumulation of synaptic vesicle-associated proteins. These findings demonstrate that axonal abnormalities including impaired cytoskeletal organization and defects in axonal transport precede demyelination in this mouse model of CMT1X. PMID:20720503

  6. 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.

  7. Abnormal calcium homeostasis in peripheral neuropathies

    PubMed Central

    Fernyhough, Paul; Calcutt, Nigel A.

    2010-01-01

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

  8. Pathogenesis of immune-mediated neuropathies.

    PubMed

    Dalakas, Marinos C

    2015-04-01

    Autoimmune neuropathies occur when immunologic tolerance to myelin or axonal antigens is lost. Even though the triggering factors and the underling immunopathology have not been fully elucidated in all neuropathy subsets, immunological studies on the patients' nerves, transfer experiments with the patients' serum or intraneural injections, and molecular fingerprinting on circulating autoantibodies or autoreactive T cells, indicate that cellular and humoral factors, either independently or in concert with each other, play a fundamental role in their cause. The review is focused on the main subtypes of autoimmune neuropathies, mainly the Guillain-Barré syndrome(s), the Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), the Multifocal Motor Neuropathy (MMN), and the IgM anti-MAG-antibody mediated neuropathy. It addresses the factors associated with breaking tolerance, examines the T cell activation process including co-stimulatory molecules and key cytokines, and discusses the role of antibodies against peripheral nerve glycolipids or glycoproteins. Special attention is given to the newly identified proteins in the nodal, paranodal and juxtaparanodal regions as potential antigenic targets that could best explain conduction failure and rapid recovery. New biological agents against T cells, cytokines, B cells, transmigration and transduction molecules involved in their immunopathologic network, are discussed as future therapeutic options in difficult cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

  9. Differential temporal expression of matrix metalloproteinases following sciatic nerve crush.

    PubMed

    Qin, Jing; Zha, Guang-Bin; Yu, Jun; Zhang, Hong-Hong; Yi, Sheng

    2016-07-01

    We previously performed transcriptome sequencing and found that genes for matrix metalloproteinases (MMPs), such as MMP7 and 12, seem to be highly upregulated following peripheral nerve injury, and may be involved in nerve repair. In the present study, we systematically determined the expression levels of MMPs and their regulators at 1, 4, 7 and 14 days after sciatic nerve crush injury. The number of differentially expressed genes was elevated at 4 and 7 days after injury, but decreased at 14 days after injury. Among the differentially expressed genes, those most up-regulated showed fold changes of more than 214, while those most down-regulated exhibited fold changes of more than 2-10. Gene sequencing showed that, at all time points after injury, a variety of MMP genes in the "Inhibition of MMPs" pathway were up-regulated, and their inhibitor genes were down-regulated. Expression of key up- and down-regulated genes was verified by quantitative real-time polymerase chain reaction analysis and found to be consistent with transcriptome sequencing. These results suggest that MMP-related genes are strongly involved in the process of peripheral nerve regeneration. PMID:27630704

  10. Differential temporal expression of matrix metalloproteinases following sciatic nerve crush

    PubMed Central

    Qin, Jing; Zha, Guang-bin; Yu, Jun; Zhang, Hong-hong; Yi, Sheng

    2016-01-01

    We previously performed transcriptome sequencing and found that genes for matrix metalloproteinases (MMPs), such as MMP7 and 12, seem to be highly upregulated following peripheral nerve injury, and may be involved in nerve repair. In the present study, we systematically determined the expression levels of MMPs and their regulators at 1, 4, 7 and 14 days after sciatic nerve crush injury. The number of differentially expressed genes was elevated at 4 and 7 days after injury, but decreased at 14 days after injury. Among the differentially expressed genes, those most up-regulated showed fold changes of more than 214, while those most down-regulated exhibited fold changes of more than 2−10. Gene sequencing showed that, at all time points after injury, a variety of MMP genes in the “Inhibition of MMPs” pathway were up-regulated, and their inhibitor genes were down-regulated. Expression of key up- and down-regulated genes was verified by quantitative real-time polymerase chain reaction analysis and found to be consistent with transcriptome sequencing. These results suggest that MMP-related genes are strongly involved in the process of peripheral nerve regeneration. PMID:27630704

  11. Rheumatoid neuropathy: a histological and electrophysiological study

    PubMed Central

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

    1970-01-01

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

  12. Pupillary signs in diabetic autonomic neuropathy.

    PubMed Central

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

    1978-01-01

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

  13. Can Diabetic Neuropathy Be Modeled In Vitro?

    PubMed

    Gardiner, N J; Freeman, O J

    2016-01-01

    Diabetic neuropathy is a common secondary complication of diabetes that impacts on patient's health and well-being. Distal axon degeneration is a key feature of diabetic neuropathy, but the pathological changes which underlie axonal die-back are incompletely understood; despite decades of research a treatment has not yet been identified. Basic research must focus on understanding the complex mechanisms underlying changes that occur in the nervous system during diabetes. To this end, tissue culture techniques are invaluable as they enable researchers to examine the intricate mechanistic responses of cells to high glucose or other factors in order to better understand the pathogenesis of nerve dysfunction. This chapter describes the use of in vitro models to study a wide range of specific cellular effects pertaining to diabetic neuropathy including apoptosis, neurite outgrowth, neurodegeneration, activity, and bioenergetics. We consider problems associated with in vitro modeling and future refinement such as use of induced pluripotent stem cells and microfluidic technology. PMID:27133145

  14. Targeting Apoptosis Signalling Kinase-1 (ASK-1) Does Not Prevent the Development of Neuropathy in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Newton, Victoria L.; Ali, Sumia; Duddy, Graham; Whitmarsh, Alan J.; Gardiner, Natalie J.

    2014-01-01

    Apoptosis signal-regulating kinase-1 (ASK1) is a mitogen-activated protein 3 kinase (MAPKKK/MAP3K) which lies upstream of the stress-activated MAPKs, JNK and p38. ASK1 may be activated by a variety of extracellular and intracellular stimuli. MAP kinase activation in the sensory nervous system as a result of diabetes has been shown in numerous preclinical and clinical studies. As a common upstream activator of both p38 and JNK, we hypothesised that activation of ASK1 contributes to nerve dysfunction in diabetic neuropathy. We therefore wanted to characterize the expression of ASK1 in sensory neurons, and determine whether the absence of functional ASK1 would protect against the development of neuropathy in a mouse model of experimental diabetes. ASK1 mRNA and protein is constitutively expressed by multiple populations of sensory neurons of the adult mouse lumbar DRG. Diabetes was induced in male C57BL/6 and transgenic ASK1 kinase-inactive (ASK1n) mice using streptozotocin. Levels of ASK1 do not change in the DRG, spinal cord, or sciatic nerve following induction of diabetes. However, levels of ASK2 mRNA increase in the spinal cord at 4 weeks of diabetes, which could represent a future target for this field. Neither motor nerve conduction velocity deficits, nor thermal or mechanical hypoalgesia were prevented or ameliorated in diabetic ASK1n mice. These results suggest that activation of ASK1 is not responsible for the nerve deficits observed in this mouse model of diabetic neuropathy. PMID:25329046

  15. 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

  16. Subacute arsenic neuropathy: clinical and electrophysiological observations.

    PubMed

    Murphy, M J; Lyon, L W; Taylor, J W

    1981-10-01

    Two patients with subacute arsenic neuropathy are described and the results of serial conduction velocity determinations from the very early stages of the illness to partial recovery are reported. Sensory and motor deficits were maximal within four weeks of the estimated time of exposure. Recovery was slow, with only partial improvement of the neurological deficits two years after onset of the illness. Progressive slowing of motor conduction velocity was observed in the first three months followed by a gradual increase in velocity thereafter. The possible mechanisms underlying the temporal profile of the electrophysiological changes are considered. The need for initiating chelation therapy before the development of the neuropathy is emphasised.

  17. Persisting nutritional neuropathy amongst former war prisoners.

    PubMed Central

    Gill, G V; Bell, D R

    1982-01-01

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

  18. The effect of pregabalin - codeine combination on partial sciatic nerve ligation - induced peripheral mononeuropathy in rats.

    PubMed

    Popa, G; Mititelu Tartau, L; Stoleriu, I; Lupusoru, R V; Lupusoru, C E; Ochiuz, L

    2016-06-01

    The present study investigates the effects of pregabalin (PGB) and codeine (COD) combination on neuropathic hyperalgesia in an animal model of peripheral nerve injury represented by partial sciatic nerve ligation. Hot plate and analgesimeter tests were performed to evaluate the influence of PGB, COD and their combination on thermal and mechanical hyperalgesia in the hind paw with partial sciatic nerve ligation. Reactivity was evaluated by measuring the latency to withdrawal of the operated hind paw from the noxious heat and pressure stimulation. Nociceptive thresholds were evaluated before (baseline) and in the 1(st), 3(rd), 5(th) and 7(th) day after surgical procedure. The investigation demonstrates that the treatment with PGB attenuated partial sciatic nerve ligation development of thermal and mechanical hyperalgesia in rats operated hind paw. The oral administration, during 14 consecutive days of PGB-COD combination significantly reduced the degree of both thermal and mechanical hyperalgesia in the hind paw with partial sciatic nerve ligation. These results suggest that the association of PGB with COD exerted ameliorative effect on partial sciatic nerve ligation-induced neuropathic pain in rats. PMID:27512007

  19. 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

  20. Relationship Between the Superior Gluteal Vessels and Nerve at the Greater Sciatic Notch.

    PubMed

    Collinge, Cory A; Ziran, Navid M; Coons, David A

    2015-10-01

    Bleeding from the superior gluteal (SG) blood vessels at the greater sciatic notch is frequently encountered during acetabular fracture surgery. The purpose of this study is to define the positional anatomy of the superior gluteal vessels and nerve (SGVAN) at the greater sciatic notch. Twenty-three hemipelvi were dissected in whole human cadavers. The greater sciatic notch and SGVAN were visualized via a posterior surgical approach, identified deep in the greater sciatic notch, and traced superficially. Branches of the SGVAN and their anatomical relationship to each other were recorded. In the notch, SG arteries comprised a single vessel in 18 (78%) of 23 specimens, with all of these dividing at varying distances (1-3.5 cm) along the lateral ilium after dividing into superior and inferior branches. The SG artery branches were contiguous with periosteum of the bony notch in all specimens. More than 1 SG nerve branch was seen in the greater sciatic notch of all specimens, including an inferior branch that exited caudal or caudal-superficial to the SG vessels. The caudal-most SG nerve branch was directly adjacent to the bony notch's periosteum in 15 (65%) of 23 specimens. The SGVAN are at risk in patients undergoing acetabular fracture surgery. Individuals performing surgery along the acetabulum's posterior column would expect to encounter a major SG nerve branch (deep inferior) before encountering the SG vessels in all cases. Iatrogenic injuries to the SGVAN might be prevented by avoiding use of cautery in this area if hemorrhage is encountered.

  1. The longitudinal epineural incision and complete nerve transection method for modeling sciatic nerve injury

    PubMed Central

    Cheng, Xing-long; Wang, Pei; Sun, Bo; Liu, Shi-bo; Gao, Yun-feng; He, Xin-ze; Yu, Chang-yu

    2015-01-01

    Injury severity, operative technique and nerve regeneration are important factors to consider when constructing a model of peripheral nerve injury. Here, we present a novel peripheral nerve injury model and compare it with the complete sciatic nerve transection method. In the experimental group, under a microscope, a 3-mm longitudinal incision was made in the epineurium of the sciatic nerve to reveal the nerve fibers, which were then transected. The small, longitudinal incision in the epineurium was then sutured closed, requiring no stump anastomosis. In the control group, the sciatic nerve was completely transected, and the epineurium was repaired by anastomosis. At 2 and 4 weeks after surgery, Wallerian degeneration was observed in both groups. In the experimental group, at 8 and 12 weeks after surgery, distinct medullary nerve fibers and axons were observed in the injured sciatic nerve. Regular, dense myelin sheaths were visible, as well as some scarring. By 12 weeks, the myelin sheaths were normal and intact, and a tight lamellar structure was observed. Functionally, limb movement and nerve conduction recovered in the injured region between 4 and 12 weeks. The present results demonstrate that longitudinal epineural incision with nerve transection can stably replicate a model of Sunderland grade IV peripheral nerve injury. Compared with the complete sciatic nerve transection model, our method reduced the difficulties of micromanipulation and surgery time, and resulted in good stump restoration, nerve regeneration, and functional recovery. PMID:26692866

  2. Bortezomib-induced painful neuropathy in rats: a behavioral, neurophysiological and pathological study in rats.

    PubMed

    Meregalli, Cristina; Canta, Annalisa; Carozzi, Valentina A; Chiorazzi, Alessia; Oggioni, Norberto; Gilardini, Alessandra; Ceresa, Cecilia; Avezza, Federica; Crippa, Luca; Marmiroli, Paola; Cavaletti, Guido

    2010-04-01

    Bortezomib is a proteasome inhibitor showing strong antitumor activity against many tumors, primarily multiple myeloma. Bortezomib-induced neuropathic pain is the main side effect and the dose-limiting factor of the drug in clinical practice. In order to obtain a pre-clinical model to reproduce the characteristic pain symptoms in bortezomib-treated patients, we developed an animal model of bortezomib-induced nociceptive sensory neuropathy. In this study, bortezomib (0.15 or 0.20mg/kg) was administered to Wistar rats three times/week for 8 weeks, followed by a 4 week follow-up period. At the end of the treatment period a significant decrease in weight gain was observed in the treated groups vs. controls, and hematological and histopathological parameters were evaluated. After the treatment period, both doses of bortezomib induced a severe reduction in nerve conduction velocity and demonstrated a dose-cumulative effect of the drug. The sensory behavioral assessment showed the onset of mechanical allodynia, while no effect on thermal perception was observed. Sciatic nerves and dorsal root ganglia (DRG) were collected at the end of the 8-week treatment and at the end of the follow-up period. The pathological examination revealed a dose-dependent axonopathy of the unmyelinated fibers in nerves of treated animals. No pathological alteration in most of DRG satellite cells and neurons was observed. Therefore, this animal model may be useful for studying the neurotoxicity and pain onset mechanisms related to bortezomib treatment.

  3. Bortezomib Treatment Produces Nocifensive Behavior and Changes in the Expression of TRPV1, CGRP, and Substance P in the Rat DRG, Spinal Cord, and Sciatic Nerve

    PubMed Central

    Quartu, M.; Carozzi, V. A.; Dorsey, S. G.; Serra, M. P.; Poddighe, L.; Picci, C.; Boi, M.; Melis, T.; Del Fiacco, M.; Meregalli, C.; Chiorazzi, A.; Renn, C. L.; Cavaletti, G.; Marmiroli, P.

    2014-01-01

    To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established “chronic” schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in thermal withdrawal latency. Western blot analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib administration. Reverse transcriptase-polymerase chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-, and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. Our findings show that bortezomib-treatment selectively affects subsets of DRG neurons likely involved in the processing of nociceptive stimuli and that neurochemical changes may contribute to development and persistence of pain in bortezomib-induced PN. PMID:24877063

  4. 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

  5. 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

  6. 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.

  7. DIABETIC NEUROPATHY PART 1: OVERVIEW AND SYMMETRIC PHENOTYPES

    PubMed Central

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

    2014-01-01

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

  8. 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.

  9. [Painful neuropathies and small fiber involvement].

    PubMed

    Lefaucheur, J-P

    2014-12-01

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

  10. Painful peripheral neuropathy and sodium channel mutations.

    PubMed

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

    2015-06-01

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

  11. 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…

  12. 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…

  13. Systemic corticosteroids in nonarteritic ischemic optic neuropathy

    PubMed Central

    Al-Zubidi, Nagham; Zhang, Jason; Spitze, Arielle; Lee, Andrew G

    2014-01-01

    Nonarteritic ischemic optic neuropathy (NAION) is one of the most prevalent optic nerve disorders seen in ophthalmic practice. The role of corticosteroid therapy in NAION remains a highly controversial area of debate in ophthalmology. This brief review will provide an overview of the current clinical evidence on this topic as well as some comment on the medical debate. PMID:25449939

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

    PubMed Central

    Liu, Guangyao; Jiang, Rui; Jin, Yan

    2014-01-01

    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. PMID:25374595

  15. Pain clinic #15. Treatment of sciatic nerve causalgia following pelvic fracture.

    PubMed

    Sullivan, R J; Thomas, P S; Geel, C V

    1990-06-01

    Direct injury to the sciatic nerve may occur in patients who sustain acetabular/pelvic fractures. Sciatic nerve causalgia has been noted in patients who suffer posterior wall acetabular fracture with or without ipsilateral hip dislocation. Sympathetic nervous system dysfunction is considered the primary cause for this syndrome, although some investigators suggest central nervous system involvement. This report documents the treatment results of three patients suffering from sciatic nerve causalgia who were referred to the Pain Treatment Center during the past year. In each case, diagnosis was confirmed by sympathetic blockade. Treatment regimens varied and included nerve blocks, cryoanalgesia techniques, and transcutaneous electrical nerve stimulation therapy. The syndrome was relieved in these patients within four to six weeks. Patients were followed for six months after initial treatment. PMID:2367147

  16. Diffusion tensor magnetic resonance imaging of regeneration/degeneration after rat sciatic nerve injury

    NASA Astrophysics Data System (ADS)

    Sig Hwang, Min; Perrin, George; Muir, David; Mareci, Thomas

    2005-11-01

    Diffusion tensor imaging was performed to investigate myelination and demyelination spatiotemporally in cut or crushed excised rat sciatic nerves in a 17.6 T magnet with a solenoid RF coil. Orientation independent measures of water diffusion, fractional anisotropy (FA) and averaged diffusivity (), were examined as MR parameters for the quantification of the myelin within the major peripheral nerve. Crushed nerves initially demonstrated decreased FA, followed by increase to FA of normal nerve with time. At 14 days post injury, FA of the nerve is high, 0.85, at the site proximal to the injury then FA decreases in a proximodistal gradient because the nerve remains more demyelinated toward the distal area. Cut sciatic nerves displayed a prolonged decrease of FA with time after injury. Also FA correlates with in these nerves. Therefore FA or may be a good indicator of myelination and demyelination in rat sciatic nerves and FA appears to be a more sensitive indicator of myelin.

  17. 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

  18. 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.

  19. 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

  20. Giant Lipomatosis of the Sciatic Nerve: Unique Magnetic Resonance Imaging Findings.

    PubMed

    Sarp, Ali Firat; Pekcevik, Yeliz

    2016-04-01

    Lipomatosis of the nerve, also known as fibrolipomatous hamartoma, is characterized by the infiltration of the nerve by fibro-fatty tissue. The affected nerve becomes thicker, and it simulates a mass lesion. Lipomatosis usually affects the median nerve and lipomatosis of the sciatic nerve is extremely rare. Magnetic resonance imaging (MRI) is the key to diagnosis, and it is usually pathognomonic. In this report, MRI and diffusion-weighted MRI findings of a case of a giant sciatic nerve lipomatosis without macrodactyly are presented. The MRI findings are unique, and awareness of the MRI features of this rare soft tissue mass may prevent unnecessary biopsies and surgeries. PMID:27679695

  1. Giant Lipomatosis of the Sciatic Nerve: Unique Magnetic Resonance Imaging Findings

    PubMed Central

    Sarp, Ali Firat; Pekcevik, Yeliz

    2016-01-01

    Lipomatosis of the nerve, also known as fibrolipomatous hamartoma, is characterized by the infiltration of the nerve by fibro-fatty tissue. The affected nerve becomes thicker, and it simulates a mass lesion. Lipomatosis usually affects the median nerve and lipomatosis of the sciatic nerve is extremely rare. Magnetic resonance imaging (MRI) is the key to diagnosis, and it is usually pathognomonic. In this report, MRI and diffusion-weighted MRI findings of a case of a giant sciatic nerve lipomatosis without macrodactyly are presented. The MRI findings are unique, and awareness of the MRI features of this rare soft tissue mass may prevent unnecessary biopsies and surgeries.

  2. Giant Lipomatosis of the Sciatic Nerve: Unique Magnetic Resonance Imaging Findings

    PubMed Central

    Sarp, Ali Firat; Pekcevik, Yeliz

    2016-01-01

    Lipomatosis of the nerve, also known as fibrolipomatous hamartoma, is characterized by the infiltration of the nerve by fibro-fatty tissue. The affected nerve becomes thicker, and it simulates a mass lesion. Lipomatosis usually affects the median nerve and lipomatosis of the sciatic nerve is extremely rare. Magnetic resonance imaging (MRI) is the key to diagnosis, and it is usually pathognomonic. In this report, MRI and diffusion-weighted MRI findings of a case of a giant sciatic nerve lipomatosis without macrodactyly are presented. The MRI findings are unique, and awareness of the MRI features of this rare soft tissue mass may prevent unnecessary biopsies and surgeries. PMID:27679695

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    2010-01-01

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

  5. 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

  6. Celecoxib accelerates functional recovery after sciatic nerve crush in the rat

    PubMed Central

    2008-01-01

    The inflammatory response appears to be essential in the modulation of the degeneration and regeneration process after peripheral nerve injury. In injured nerves, cyclooxygenase-2 (COX-2) is strongly upregulated around the injury site, possibly playing a role in the regulation of the inflammatory response. In this study we investigated the effect of celecoxib, a COX-2 inhibitor, on functional recovery after sciatic nerve crush in rats. Unilateral sciatic nerve crush injury was performed on 10 male Wistar rats. Animals on the experimental group (n = 5) received celecoxib (10 mg/kg ip) immediately before the crush injury and daily for 7 days after the injury. Control group (n = 5) received normal saline at equal regimen. A sham group (n = 5), where sciatic nerve was exposed but not crushed, was also evaluated. Functional recovery was then assessed by calculating the sciatic functional index (SFI) on days 0,1,7,14 and 21 in all groups, and registering the day of motor and walking onset. In comparison with control group, celecoxib treatment (experimental group) had significant beneficial effects on SFI, with a significantly better score on day 7. Anti-inflammatory drug celecoxib should be considered in the treatment of peripheral nerve injuries, but further studies are needed to explain the mechanism of its neuroprotective effects. PMID:19036161

  7. Gait phase detection from sciatic nerve recordings in functional electrical stimulation systems for foot drop correction.

    PubMed

    Chu, Jun-Uk; Song, Kang-Il; Han, Sungmin; Lee, Soo Hyun; Kang, Ji Yoon; Hwang, Dosik; Suh, Jun-Kyo Francis; Choi, Kuiwon; Youn, Inchan

    2013-05-01

    Cutaneous afferent activities recorded by a nerve cuff electrode have been used to detect the stance phase in a functional electrical stimulation system for foot drop correction. However, the implantation procedure was difficult, as the cuff electrode had to be located on the distal branches of a multi-fascicular nerve to exclude muscle afferent and efferent activities. This paper proposes a new gait phase detection scheme that can be applied to a proximal nerve root that includes cutaneous afferent fibers as well as muscle afferent and efferent fibers. To test the feasibility of this scheme, electroneurogram (ENG) signals were measured from the rat sciatic nerve during treadmill walking at several speeds, and the signal properties of the sciatic nerve were analyzed for a comparison with kinematic data from the ankle joint. On the basis of these experiments, a wavelet packet transform was tested to define a feature vector from the sciatic ENG signals according to the gait phases. We also propose a Gaussian mixture model (GMM) classifier and investigate whether it could be used successfully to discriminate feature vectors into the stance and swing phases. In spite of no significant differences in the rectified bin-integrated values between the stance and swing phases, the sciatic ENG signals could be reliably classified using the proposed wavelet packet transform and GMM classification methods.

  8. 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

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

    PubMed Central

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

    2013-01-01

    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. PMID:25206634

  10. 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

  11. Detection of Position-Related Sciatic Nerve Dysfunction by Somatosensory Evoked Potentials During Spinal Surgery.

    PubMed

    Rice, Kent; Scott, Andrew; Guyot, Anne

    2015-06-01

    It is well established that intraoperative somatosensory evoked potentials (SSEPs) are sensitive to plexus and peripheral nerve dysfunction related to malpositioning of patients during spinal surgery. While most reports focus on upper extremity nerve or brachial plexus effects, there is very little on detection of sciatic nerve compromise. Recording of the SSEP at the popliteal fossa is a common strategy to aid in troubleshooting stimulus-related problems or distal peripheral tibial nerve failure; yet position-related sciatic nerve effects may not be realized by changes in the popliteal fossa response. Three posterior lumbar surgeries are reviewed in which there was evidence of proximal lower extremity peripheral nerve dysfunction related to positioning. Loss of posterior tibial nerve SSEPs with preservation of the peripheral popliteal fossa response recording occurred in the absence of critical surgical manipulations. Efforts at repositioning and release of tension on the lower limbs promptly resulted in recovey of lost responses. Two of the three cases involved patients in a kneeling position with a tight strap across the posterior thigh. Standard SSEP recordings used in intraoperative neuromonitoring do not specifically localize intraoperative changes to the sciatic nerve; thus, such changes affecting SSEPs above the popliteal fossa mimic iatrogenic changes occurring at the surgical site. These case reports show that when the stage of surgery does not support iatrogenic changes, malpositioning affecting sciatic nerve should be considered, especially for patients placed in a kneeling position on an Andrews frame.

  12. 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.

  13. 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.

  14. Suprascapular neuropathy in a collegiate pitcher.

    PubMed

    Smith, A N

    1995-03-01

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

  15. Immediate and short-term pain relief by acute sciatic nerve press: a randomized controlled trial

    PubMed Central

    He, Jiman; Wu, Bin; Zhang, Wenlong; Ten, Guangping

    2007-01-01

    Background Despite much research, an immediately available, instantly effective and harmless pain relief technique has not been discovered. This study describes a new manipulation: a "2-minute sciatic nerve press", for rapid short-term relief of pain brought on by various dental and renal diseases. Methods This randomized, single-blind, placebo-controlled trial ran in three hospitals in Anhui Province, China, with an enrollment of 66 out of 111 solicited patients aged 16 to 74 years. Patients were recruited sequentially, by specific participating physicians at their clinic visits to three independent hospitals. The diseases in enrolled dental patients included dental caries, periodontal diseases and dental trauma. Renal diseases in recruits included kidney infections, stones and some other conditions. Patients were randomly assigned to receive the "2-minute sciatic nerve press" or the "placebo press". For the "2-minute sciatic nerve press", pressure was applied simultaneously to the sciatic nerves at the back of the thighs, using the fists while patients lay prone. For the "placebo press", pressure was applied simultaneously to a parallel spot on the front of the thighs, using the fists while patients lay supine. Each fist applied a pressure of 11 to 20 kg for 2 minutes, after which, patients arose to rate pain. Results The "2-minute sciatic nerve press" produced greater pain relief than the "placebo press". Within the first 10 minutes after sciatic pressure, immediate pain relief ratings averaged 66.4% (p < 0.001) for the dental patients, versus pain relief of 20% for the placebo press, and, 52.2% (p < 0.01) for the renal patients, versus relief of 14% for the placebo press, in median. The method worked excellently for dental caries and periodontal diseases, but poorly for dental trauma. Forty percent of renal patients with renal colic did not report any pain relief after the treatment. Conclusion Two minutes of pressure on both sciatic nerves can produce

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

    PubMed

    Garb, L G; Hine, C H

    1977-08-01

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

  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. 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

  19. Neuropathic pain in hereditary peripheral neuropathy

    PubMed Central

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

    2013-01-01

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

  20. Diabetes, Peripheral Neuropathy, and Lower Extremity Function

    PubMed Central

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

    2014-01-01

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

  1. PMP22 related congenital hypomyelination neuropathy.

    PubMed

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

    2001-01-01

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

  2. Inherited peripheral neuropathies due to mitochondrial disorders.

    PubMed

    Cassereau, J; Codron, P; Funalot, B

    2014-05-01

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

  3. 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.

  4. Acrylamide administration alters protein phosphorylation and phospholipid metabolism in rat sciatic nerve

    SciTech Connect

    Berti-Mattera, L.N.; Eichberg, J.; Schrama, L.; LoPachin, R.M. )

    1990-05-01

    The effects of ACR on protein phosphorylation and phospholipid metabolism were assessed in rat sciatic nerve. After 5 days of ACR administration (50 mg/kg/day) an increase in the incorporation of 32P into phosphatidylinositol-4,5-bisphosphate, phosphatidylinositol-4-phosphate, and phosphatidylcholine was detected in proximal sciatic nerve segments. In contrast, no changes in phospholipid metabolism were observed in distal segments. After 9 days of ACR treatment when neurotoxicological symptoms were clearly apparent, a generalized increase in radiolabel uptake into phospholipids was noted exclusively in proximal nerve regions. ACR-induced increases in phospholipid metabolism were toxicologically specific since comparable administration of MBA (108 mg/kg/day X 5 or 9 days) produced only minor changes. ACR intoxication was also associated with a rise in sciatic nerve protein phosphorylation. After 9 days of ACR treatment, phosphorylation of beta-tubulin, P0, and several unidentified proteins (38 and 180 kDa) was increased in distal segments. In contrast, chronic administration of MBA caused increases in phosphorylation of beta-tubulin and the major myelin proteins of proximal nerve segments. In cell free homogenates prepared from sciatic nerves of treated and control rats, MBA caused an increase in phosphorylation of major myelin proteins similar to its effect in intact proximal nerve segments. The most striking effect observed in nerve homogenates of ACR-treated rats was a marked decrease in phosphorylation of an 80-kDa protein. Addition of ACR (1 mM) to homogenates of normal nerve had no effect on protein phosphorylation. Our results indicate that changes in the phosphorylation of phospholipids and proteins in sciatic nerve might be a component of the neurotoxic mechanism of ACR.

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

    PubMed

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

    1994-01-01

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

  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. Diabetic neuropathy part 2: proximal and asymmetric phenotypes.

    PubMed

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

    2013-05-01

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

  8. Abnormal Nutritional Factors in Patients Evaluated at a Neuropathy Center.

    PubMed

    Latov, Norman; Vo, Mary L; Chin, Russell L; Carey, Bridget T; Langsdorf, Jennifer A; Feuer, Naomi T

    2016-06-01

    Abnormal concentrations of nutritional factors were found in 24.1% of 187 patients with neuropathy who were newly seen at our academic neuropathy referral center over a 1-year period. All patients presented with sensory axonal or small fiber neuropathy. In 7.3%, they were present in association with at least one other identifiable cause for neuropathy. Elevated levels of pyridoxal phosphate or mercury occurred more frequently than deficiencies in vitamins B1, B12, or B6. The nutritional abnormalities are amenable to correction by dietary intervention. PMID:27224436

  9. 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.

  10. Axonal Pathology Precedes Demyelination in a Mouse Model of X-Linked Demyelinating/ Type I Charcot-Marie Tooth (CMT1X) Neuropathy

    PubMed Central

    Vavlitou, Natalie; Sargiannidou, Irene; Markoullis, Kyriaki; Kyriacou, Kyriacos; Scherer, Steven S.; Kleopa, Kleopas A.

    2010-01-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is an inherited peripheral neuropathy caused by mutations in GJB1, the gene that encodes the gap junction protein connexin32 (Cx32). Cx32 is expressed by myelinating Schwann cells and forms gap junctions in non-compact myelin areas but axonal involvement is more prominent in X-linked compared to other forms of demyelinating Charcot-Marie-Tooth disease. To clarify the cellular and molecular mechanisms of axonal pathology in CMT1X, we studied Gjb1-null mice at early stages (i.e. 2- to 4-month-old) of the neuropathy, when there is minimal or no demyelination. The diameters of large myelinated axons were progressively reduced in Gjb1-null mice compared to those in wild type littermates. Furthermore, neurofilaments were relatively more dephosphorylated and more densely packed starting at 2 months of age. Increased expression of β-amyloid precursor protein, a marker of axonal damage, was also detected in Gjb1-null nerves. Finally, fast axonal transport, assayed by sciatic nerve ligation experiments, was slower in distal axons of Gjb1-null vs. wild type animals with reduced accumulation of synaptic vesicle-associated proteins. These findings demonstrate that axonal abnormalities including impaired cytoskeletal organization and defects in axonal transport precede demyelination in this mouse model of CMT1-X. PMID:20720503

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

    PubMed Central

    Patzkó, Ágnes; 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

    2012-01-01

    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. PMID:23250879

  12. 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. PMID:23250879

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

    PubMed Central

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

    2010-01-01

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

  14. Molecular alterations underlie nodal and paranodal degeneration in type 1 diabetic neuropathy and are prevented by C-peptide.

    PubMed

    Sima, Anders A F; Zhang, Weixian; Li, Zhen-Guo; Murakawa, Yuichi; Pierson, Christopher R

    2004-06-01

    To explore the molecular abnormalities underlying the degeneration of the node of Ranvier, a characteristic aberration of type 1 diabetic neuropathy, we examined in type 1 BB/Wor and type 2 BBZDR/Wor rats changes in expression of key molecules that make up the nodal and paranodal apparatus of peripheral nerve. Their posttranslational modifications were examined in vitro. Their responsiveness to restored insulin action was examined in type 1 animals replenished with proinsulin C-peptide. In sciatic nerve, the expression of contactin, receptor protein tyrosine phosphatase beta, and the Na(+)-channel beta(1) subunit, paranodal caspr and nodal ankyrin(G) was unaltered in 2-month type 1 diabetic BB/Wor rats but significantly decreased after 8 months of diabetes. These abnormalities were prevented by C-peptide administered to type 1 BB/Wor rats and did not occur in duration- and hyperglycemia-matched type 2 BBZDR/Wor rats. The expression of the alpha-Na(+)-channel subunit was unaltered. In SH-SY5Y cells, only the combination of insulin and C-peptide normalized posttranslational O-linked N-acetylglucosamine modifications and maximized serine phosphorylation of ankyrin(G) and p85 binding to caspr. The beneficial effects of C-peptide resulted in significant normalization of the nerve conduction deficits. These data describe for the first time the progressive molecular aberrations underlying nodal and paranodal degenerative changes in type 1 diabetic neuropathy and demonstrate that they are preventable by insulinomimetic C-peptide. PMID:15161761

  15. 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. PMID:25119457

  16. 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

  17. Lithium-Induced Motor Neuropathy: An Unusual Presentation

    PubMed Central

    Mohapatra, Satyakam; Sahoo, Manas Ranjan; Rath, Neelmadhav

    2016-01-01

    Peripheral neuropathy secondary to lithium is under-recognized. Most cases of polyneuropathy were reported with lithium intoxication. However, very few cases were reported without lithium toxicity. We present a case of motor neuropathy due to the use of lithium in a 26-year-old male with a therapeutic lithium level. PMID:27335523

  18. Isolated musculocutaneous neuropathy caused by a proximal humeral exostosis.

    PubMed

    Juel, V C; Kiely, J M; Leone, K V; Morgan, R F; Smith, T; Phillips, L H

    2000-01-25

    We report an isolated musculocutaneous neuropathy caused by a proximal humeral osteochondroma that became symptomatic after the patient played recreational basketball. Lesion resection resulted in complete deficit resolution. Mass lesions involving the musculocutaneous nerve should be considered in patients with atraumatic, isolated musculocutaneous neuropathies that are recurrent or fail to recover, even in the setting of strenuous exercise.

  19. Reinnervation of the Tibialis Anterior Following Sciatic Nerve Crush Injury: A Confocal Microscopic Study in Transgenic Mice

    PubMed Central

    Magill, Christina K.; Tong, Alice; Kawamura, David; Hayashi, Ayato; Hunter, Daniel A.; Parsadanian, Alexander; Mackinnon, Susan E.; Myckatyn, Terence M.

    2007-01-01

    Transgenic mice whose axons and Schwann cells express fluorescent chromophores enable new imaging techniques and augment concepts in developmental neurobiology. The utility of these tools in the study of traumatic nerve injury depends on employing nerve models that are amenable to microsurgical manipulation and gauging functional recovery. Motor recovery from sciatic nerve crush injury is studied here by evaluating motor endplates of the tibialis anterior muscle, which is innervated by the deep peroneal branch of the sciatic nerve. Following sciatic nerve crush, the deep surface of the tibialis anterior muscle is examined using whole mount confocal microscopy, and reinnervation is characterized by imaging fluorescent axons or Schwann cells (SCs). One week following sciatic crush injury, 100% of motor endplates are denervated with partial reinnervation at two weeks, hyperinnervation at three and four weeks, and restoration of a 1:1 axon to motor endplate relationship six weeks after injury. Walking track analysis reveals progressive recovery of sciatic nerve function by six weeks. SCs reveal reduced S100 expression within two weeks of denervation, correlating with regression to a more immature phenotype. Reinnervation of SCs restores S100 expression and a fully differentiated phenotype. Following denervation, there is altered morphology of circumscribed terminal Schwann cells demonstrating extensive process formation between adjacent motor endplates. The thin, uniformly innervated tibialis anterior muscle is well suited for studying motor reinnervation following sciatic nerve injury. Confocal microscopy may be performed coincident with other techniques of assessing nerve regeneration and functional recovery. PMID:17628540

  20. 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

  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. 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

  3. Optic neuropathy associated with periostitis in relapsing polychondritis.

    PubMed

    Hirunwiwatkul, Parima; Trobe, Jonathan D

    2007-03-01

    Optic neuropathy is an uncommon manifestation of relapsing polychondritis (RPC), a rare systemic disease affecting cartilaginous and proteoglycan-rich structures. The optic neuropathy has been attributed to ischemia, intrinsic inflammation of the optic nerve, or spread of inflammation to the nerve from adjacent intraconal orbital tissues. We report a case of recurrent corticosteroid-responsive optic neuropathy in which MRI did not show ocular, optic nerve, or intraconal orbital abnormalities but did show periosteal thickening and enhancement in the apical orbit and adjacent intracranial space consistent with periostitis. The periostitis, which is a manifestation of a systemic vasculitis or an autoimmune reaction to progenitors of cartilage, probably caused the optic neuropathy by compression or inflammation. It is important to recognize this mechanism of optic neuropathy as its imaging features may be a subtle yet critical clue to an underlying systemic condition that can be life-threatening if not properly managed.

  4. Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency

    PubMed Central

    Yaghini, Omid

    2016-01-01

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

  5. Clinical features and electrodiagnosis of ulnar neuropathies.

    PubMed

    Landau, Mark E; Campbell, William W

    2013-02-01

    In this review, we delineate clinical, electrodiagnostic, and radiographic features of ulnar mononeuropathies. Ulnar neuropathy at the elbow (UNE) is most commonly due to lesions at the level of the retroepicondylar groove (RTC), with approximately 25% at the humeroulnar arcade (HUA). The term 'cubital tunnel syndrome' should be reserved for the latter. The diagnostic accuracy of nerve conduction studies is limited by biological (e.g. low elbow temperature) and technical factors. Across-elbow distance measurements greater than 10 cm improve diagnostic specificity at the expense of decreased sensitivity. Short-segment incremental studies can differentiate lesions at the HUA from those at the RTC.

  6. Acute Toxic Neuropathy Mimicking Guillain Barre Syndrome

    PubMed Central

    Jalal, Muhammed Jasim Abdul; Fernandez, Shirley Joan; Menon, Murali Krishna

    2015-01-01

    Case: A 30 year old male presented with numbness of palms and soles followed by weakness of upper limbs and lower limbs of 5 days duration, which was ascending and progressive. Three months back he was treated for oral and genital ulcers with oral steroids. His ulcers improved and shifted to indigenous medication. His clinical examination showed polyneuropathy. CSF study did not show albuminocytological dissociation. Nerve conduction study showed demyelinating polyneuropathy. His blood samples and the ayurvedic drug samples were sent for toxicological analysis. Inference: Acute toxic neuropathy - Arsenic PMID:25811007

  7. 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

  8. [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.

  9. [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.

  10. 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.

  11. 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. PMID:25674823

  12. 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.

  13. Bone Marrow Mesenchymal Stem Cell and Vein Conduit on Sciatic Nerve Repair in Rats

    PubMed Central

    Seyed Foroutan, Kamal; Khodarahmi, Ali; Alavi, Hootan; Pedram, Sepehr; Baghaban Eslaminejad, Mohamad Reza; Bordbar, Sima

    2015-01-01

    Background: Peripheral nerve repair with sufficient functional recovery is an important issue in reconstructive surgery. Stem cells have attracted extensive research interest in recent years. Objectives: The purpose of this study was to compare the vein conduit technique, with and without the addition of mesenchymal stem cells in gap-less nerve injury repair in rats. Materials and Methods: In this study, 36 Wistar rats were randomly allocated to three groups: In the first group, nerve repair was performed with simple neurorrhaphy (control group), in the second group, nerve repair was done with vein conduit over site (vein conduit group) and in the third group, bone marrow stem cells were instilled into the vein conduit (stem cell group) after nerve repair with vein conduit over site. Six weeks after the intervention, the sciatic function index, electrophysiological study and histological examination were performed. Results: All animals tolerated the surgical procedures and survived well. The sciatic function index and latency were significantly improved in the vein conduit (P = 0.04 and 0.03, respectively) and stem cell group (P = 0.02 and 0.03, respectively) compared with the control group. No significant difference was observed in sciatic function and latency between the vein conduit and stem-cell groups. Moreover, histological analysis showed no significant difference in regenerative density between these two groups. Conclusions: The results of this study showed that the meticulous microsurgical nerve repair, which was performed using the vein tubulization induced significantly better sciatic nerve regeneration. However, the addition of bone marrow mesenchymal stem cell to vein conduit failed to promote any significant changes in regeneration outcome. PMID:25825699

  14. [Morphometric analysis of the sciatic nerve and its principal branches in the pigeon (Columba livia)].

    PubMed

    Vita, G; Muglia, U; Ciriaco, E; Gugliotta, M A; Abbate, F; Laurà, R; Germanà, G P; Germanà, G

    1991-01-01

    The methodological approach used in this study is to characterize the number, the density and the diameter distribution of myelinated fibers (MFs) and unmyelinated fibers (UMFs) in sciatic nerve and its main branches of pigeon. The results have shown that the fiber composition is quite variable because in pigeon there are relatively MF with thin myelin sheaths and MF with thicker sheaths. Our data suggest that morphometric analysis could represent a helpful methodological approach to better characterize these systems.

  15. 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

  16. Allograft pretreatment for the repair of sciatic nerve defects: green tea polyphenols versus radiation

    PubMed Central

    Zhou, Sheng-hu; Zhen, Ping; Li, Shen-song; Liang, Xiao-yan; Gao, Ming-xuan; Tian, Qi; Li, Xu-sheng

    2015-01-01

    Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can eliminate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, improve tissue preservation, and minimize postoperative infection. In the present study, we investigate which intervention achieves better results. We produced a 1.0 cm sciatic nerve defect in rats, and divided the rats into four treatment groups: autograft, fresh nerve allograft, green tea polyphenol-pretreated (1 mg/mL, 4°C) nerve allograft, and irradiation-pretreated nerve allograft (26.39 Gy/min for 12 hours; total 19 kGy). The animals were observed, and sciatic nerve electrophysiology, histology, and transmission electron microscopy were carried out at 6 and 12 weeks after grafting. The circumference and structure of the transplanted nerve in rats that received autografts or green tea polyphenol-pretreated nerve allografts were similar to those of the host sciatic nerve. Compared with the groups that received fresh or irradiation-pretreated nerve allografts, motor nerve conduction velocity in the autograft and fresh nerve allograft groups was greater, more neurites grew into the allografts, Schwann cell proliferation was evident, and a large number of new blood vessels was observed; in addition, massive myelinated nerve fibers formed, and abundant microfilaments and microtubules were present in the axoplasm. Our findings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to transplanting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation. PMID:25788934

  17. Embolization for a bleeding pelvic fracture in a patient with persistent sciatic artery.

    PubMed

    Hiki, Taro; Okada, Yoshitaka; Wake, Kouji; Fujiwara, Atsushi; Kaji, Yasushi

    2007-04-01

    Emergency embolization for a bleeding pelvic fracture was performed in a patient with persistent sciatic artery, a rare anatomic variation in which the internal iliac artery continues to the popliteal artery. Successful hemostasis was achieved without complications by means of selective catheterization into each branch of the internal iliac artery. Awareness of this unusual vascular anatomy is critically important to avoid serious complication of emergency embolization.

  18. Extensive propagation of a pancreatic pseudocyst along the lower limb through the sciatic foramen.

    PubMed

    Coulier, B; Maldague, P; Bueres-Dominguez, I; Ramboux, A; Pierard, F; Bienfait, B

    2012-01-01

    The extremely rare extensive propagation of a giant retroperitoneal pancreatic pseudocyst into the posterior compartment of the lower limb as far as the knee is reported. The extension was found producing through the sciatic foramen and the full diagnosis was made by MDCT. A complete healing was progressively obtained in the 78-year old female after a six months period of sequential multidisciplinary therapeutic approach comprising combined medical and surgical intra-abdominal and external drainage.

  19. 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

  20. 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

  1. 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

  2. Effects of 940 nm light-emitting diode (led) on sciatic nerve regeneration in rats.

    PubMed

    Serafim, Karla Guivernau Gaudens; Ramos, Solange de Paula; de Lima, Franciele Mendes; Carandina, Marcelo; Ferrari, Osny; Dias, Ivan Frederico Lupiano; Toginho Filho, Dari de Oliveira; Siqueira, Cláudia Patrícia Cardoso Martins

    2012-01-01

    The objective of the present study was to evaluate the effect of 940 nm wavelength light emitting diode (LED) phototherapy on nerve regeneration in rats. Forty male Wistar rats weighing approximately 300 g each were divided into four groups: control (C); control submitted to LED phototherapy (CLed); Sciatic Nerve Lesion without LED phototherapy (L); Sciatic Nerve Lesion with LED phototherapy (LLed). The lesion was caused by crushing the right sciatic nerve. A dose of 4 J/cm(2) was used for ten consecutive days beginning on the first postoperative day. Groups C and L were submitted to the same procedure as the LLed group, but the equipment was turned off. The LED phototherapy with 940 nm wavelength reduced the areas of edema, the number of mononuclear cells present in the inflammatory infiltration, and increased functional recovery scores at 7, 14 and 21 days. The results suggest that the use of phototherapy at 940 nm after nerve damage improves morphofunctional recovery and nerve regeneration. PMID:21547474

  3. Effects of 940 nm light-emitting diode (led) on sciatic nerve regeneration in rats.

    PubMed

    Serafim, Karla Guivernau Gaudens; Ramos, Solange de Paula; de Lima, Franciele Mendes; Carandina, Marcelo; Ferrari, Osny; Dias, Ivan Frederico Lupiano; Toginho Filho, Dari de Oliveira; Siqueira, Cláudia Patrícia Cardoso Martins

    2012-01-01

    The objective of the present study was to evaluate the effect of 940 nm wavelength light emitting diode (LED) phototherapy on nerve regeneration in rats. Forty male Wistar rats weighing approximately 300 g each were divided into four groups: control (C); control submitted to LED phototherapy (CLed); Sciatic Nerve Lesion without LED phototherapy (L); Sciatic Nerve Lesion with LED phototherapy (LLed). The lesion was caused by crushing the right sciatic nerve. A dose of 4 J/cm(2) was used for ten consecutive days beginning on the first postoperative day. Groups C and L were submitted to the same procedure as the LLed group, but the equipment was turned off. The LED phototherapy with 940 nm wavelength reduced the areas of edema, the number of mononuclear cells present in the inflammatory infiltration, and increased functional recovery scores at 7, 14 and 21 days. The results suggest that the use of phototherapy at 940 nm after nerve damage improves morphofunctional recovery and nerve regeneration.

  4. A computational model for the stimulation of rat sciatic nerve using a transverse intrafascicular multichannel electrode.

    PubMed

    Raspopovic, Stanisa; Capogrosso, Marco; Micera, Silvestro

    2011-08-01

    Neuroprostheses based on electrical stimulation could potentially help disabled persons. They are based on neural interface that aim at creating an intimate contact with neural cells. The efficacy of neuroprostheses can be improved by increasing the selectivity of the neural interfaces used to stimulate specific subsets of cells. Selectivity is strongly influenced by interface design. Computer models can be useful for exploring the high dimensional space of design parameters with the aim to provide guidelines for the development of more efficient electrodes, with minimal animal use and optimization of manufacturing processes. The purpose of this study was to implement a realistic model of the performance of a transverse intrafascicular multichannel electrode (TIME) implanted into the rat sciatic nerve. A realistic finite element method (FEM) model was developed taking into account the anatomical and physiological features of the rat sciatic nerve. Electric potentials were calculated and interpolated voltages were applied to the model of a rat sciatic nerve axon, based on experimental biophysical data. Results indicate that high intra-fascicular and inter-fascicular selectivity values with low current levels can be achieved with TIMEs. The selectivity of TIMEs was also compared to an extraneural electrode, showing that higher selectivity with less current can be obtained. Using this model, the robustness of electrode performances for translational and rotational displacements were evaluated.

  5. Up-regulation of NF45 correlates with Schwann cell proliferation after sciatic nerve crush.

    PubMed

    Wang, Youhua; Zhou, Shiran; Xu, Hua; Yan, Shixian; Xu, Dawei; Zhang, Yi

    2015-05-01

    Nuclear factor (NF)45 (also known as interleukin enhancer-binding factor (ILF)2), is a transcription factor that interacts with NF90 to regulate gene expression. It has long been implicated in the regulation of cell proliferation. However, the role of NF45 in the process of peripheral nervous system regeneration after injury remains poorly understood. Herein, we investigated the spatiotemporal expression of NF45 in a rat sciatic nerve crush model. We detected the up-regulated expression of NF45 in Schwann cell after sciatic nerve crush. What's more, the expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA) exhibited a similar tendency with that of NF45. In cell cultures, we observed increased expression of NF45 during the process of TNF-α-induced Schwann cell proliferation, whereas the protein level of p21 was down-regulated. Interference of NF45 led to enhanced expression of p21 and also impaired proliferation of Schwan cells. Taken together, our data implicated that NF45 was up-regulated in the sciatic nerve after crush, which was associated with proliferation of Schwann cell.

  6. 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.

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

    PubMed

    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

  8. 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.

  9. 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

  10. 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. PMID:22773531

  11. In Vivo Gene Transfer to Schwann Cells in the Rodent Sciatic Nerve by Electroporation.

    PubMed

    Ino, Daisuke; Iino, Masamitsu

    2016-01-01

    The formation of the myelin sheath by Schwann cells (SCs) is essential for rapid conduction of nerve impulses along axons in the peripheral nervous system. SC-selective genetic manipulation in living animals is a powerful technique for studying the molecular and cellular mechanisms of SC myelination and demyelination in vivo. While knockout/knockin and transgenic mice are powerful tools for studying SC biology, these methods are costly and time consuming. Viral vector-mediated transgene introduction into the sciatic nerve is a simpler and less laborious method. However, viral methods have limitations, such as toxicity, transgene size constraints, and infectivity restricted to certain developmental stages. Here, we describe a new method that allows selective transfection of myelinating SCs in the rodent sciatic nerve using electroporation. By applying electric pulses to the sciatic nerve at the site of plasmid DNA injection, genes of interest can be easily silenced or overexpressed in SCs in both neonatal and more mature animals. Furthermore, this in vivo electroporation method allows for highly efficient simultaneous expression of multiple transgenes. Our novel technique should enable researchers to efficiently manipulate SC gene expression, and facilitate studies on SC development and function. PMID:27683960

  12. 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.

  13. A review of primary hereditary optic neuropathies.

    PubMed

    Votruba, M; Aijaz, S; Moore, A T

    2003-01-01

    The primary inherited optic neuropathies are a heterogeneous group of disorders that result in loss of retinal ganglion cells, leading to the clinical appearance of optic atrophy. They affect between 1:10,000 to 1:50,000 people. The main clinical features are a reduction in visual acuity, colour vision abnormalities, centro-caecal visual field defects and pallor of the optic nerve head. Electrophysiological testing shows a normal flash electroretinogram, absent or delayed pattern visually evoked potentials suggestive of a conduction deficit and N95 waveform reduction on the pattern electroretinogram, consistent with a primary ganglion cell pathology. The primary inherited optic neuropathies may be sporadic or familial. The mode of inheritance may be autosomal dominant, autosomal recessive, X-linked recessive or mitochondrial. Within each of these groups, the phenotypic characteristics vary in such features as the mode and age of onset, the severity of the visual loss, the colour deficit and the overall prognosis. A number of different genes (most as yet unidentified) in both nuclear and mitochondrial genomes, underlie these disorders. The elucidation of the role of the encoded proteins will improve our understanding of basic mechanisms of ganglion cell development, physiology and metabolism and further our understanding of the pathophysiology of optic nerve disease. It will also improve diagnosis, counselling and management of patients, and eventually lead to the development of new therapeutic modalities.

  14. Treating Painful Diabetic Peripheral Neuropathy: An Update.

    PubMed

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

    2016-08-01

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

  15. 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.

  16. Molecular genetics of hereditary sensory neuropathies.

    PubMed

    Auer-Grumbach, Michaela; Mauko, Barbara; Auer-Grumbach, Piet; Pieber, Thomas R

    2006-01-01

    Hereditary sensory neuropathies (HSN), also known as hereditary sensory and autonomic neuropathies (HSAN), are a clinically and genetically heterogeneous group of disorders. They are caused by neuronal atrophy and degeneration, predominantly affecting peripheral sensory and autonomic neurons. Both congenital and juvenile to adulthood onset is possible. Currently, the classification of the HSN depends on the mode of inheritance, age at onset, and clinical presentation. Hallmark features are progressive sensory loss, chronic skin ulcers, and other skin abnormalities. Spontaneous fractures and neuropathic arthropathy are frequent complications and often necessitate amputations. Autonomic features vary between different subgroups. Distal muscle weakness and wasting may be present and is sometimes so prominent that it becomes difficult to distinguish HSN from Charcot-Marie-Tooth syndrome. Recent major advances in molecular genetics have led to the identification of seven gene loci and six-disease causing genes for autosomal-dominant and autosomal-recessive HSN. These genes have been shown to play roles in lipid metabolism and the regulation of intracellular vesicular transport, but also a presumptive transcriptional regulator, a nerve growth factor receptor, and a nerve growth factor have been described among the causative genes in HSN. Nevertheless, it remains unclear how mutations in the known genes lead to the phenotype of HSN. In this review, we summarize the recent progress of the molecular genetics of the HSN and the implicated genes. PMID:16775373

  17. Congenital hypomyelinating neuropathy: a reversible case.

    PubMed

    Ghamdi, M; Armstrong, D L; Miller, G

    1997-01-01

    A boy was born at 39 weeks gestation with severe weakness and hypotonia, fractured femurs, poor suck and swallow, and absent deep tendon reflexes. Electrodiagnostic studies revealed marked slowing of motor nerve conduction velocities and normal muscle electrical activity with no evidence of acute denervation. Muscle biopsy showed mild type 2 fiber predominance, and sural nerve biopsy revealed large axons without myelin, and axons with insufficient amount of myelin for their diameter. There was no evidence of inflammation or demyelination. Gradual clinical improvement in tone and strength occurred in a cephalocaudal direction. By 4 months, motor nerve conduction velocities and clinical examination were normal apart from absent deep tendon reflexes. On review at 19 months, motor development and neurological examination were completely normal. Pathogenesis of this reversible pathologically documented case of congenital hypomyelinating neuropathy is unclear. No evidence was found for an inflammatory, toxic, metabolic, or demyelinating cause. Abnormal expression of a developmental gene, as in reversible cytochrome oxidase deficiency, may be a cause of this neuropathy.

  18. 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

  19. Symptoms: Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

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

    2015-01-01

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

  20. 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

  1. 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.

  2. 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.

  3. Identifying Common Genetic Risk Factors of Diabetic Neuropathies

    PubMed Central

    Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879

  4. 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

  5. Treatment of postoperative sciatic nerve palsy after total hip arthroplasty for postoperative acetabular fracture: A case report.

    PubMed

    Kanda, Akio; Kaneko, Kazuo; Obayashi, Osamu; Mogami, Atsuhiko; Morohashi, Itaru

    2016-11-01

    Acetabular fracture is usually treated with osteosynthesis. However, in the case of an intra-articular fracture, osteosynthesis can result in arthropathy of the hip joint and poor long-term results, hence, total hip arthroplasty is required. However, in total hip arthroplasty for postoperative acetabular fracture, sciatic nerve palsy tends to develop more commonly than after primary total hip arthroplasty. This is a case report of a 57-year-old Japanese male who had internal skeletal fixation for a left acetabular fracture that had occurred 2 years earlier. One year later, he developed coxarthrosis and severe pain of the hip joint and total hip arthroplasty was performed. After the second surgery, he experienced pain along the distribution of the sciatic nerve and weakness of the muscles innervated by the peroneal nerve, indicating sciatic nerve palsy. We performed a third operation, and divided adhesions around the sciatic nerve. Postoperatively, the anterior hip joint pain and the buttocks pain when the hip was flexed were improved. Abduction of the fifth toe was also improved. However, the footdrop and sensory disturbance were not improved. A year after the third operation, sensory disturbance was slightly improved but the footdrop was not improved. We believe the sciatic nerve palsy developed when we dislocated the hip joint as the sciatic nerve was excessively extended as the hip joint flexed and internally rotated. Sciatic nerve adhesion can occur easily in total hip replacement for postoperative acetabular fracture; hence, adhesiotomy should be conducted before performing hip dislocation to prevent injury caused by nerve tension. The patient agreed that the details of this case could be submitted for publication. The work has been reported in line with the CARE criteria and cite. PMID:27672438

  6. Spheniodal mucocele causing bilateral optic neuropathy and ophthalmoplegia

    PubMed Central

    Selvakumar, Ambika; Mahalaxmi, Balasubramanyam; Ananth, V; Gautam, Cugati

    2014-01-01

    Sphenoid sinus mucocele comprises only 2% of all paranasal sinus mucoceles. In literature, there is a case report on sphenoidal mucocele causing bilateral optic neuropathy, with unilateral partial recovery and cranial nerve palsy, but we did not come across any literature with bilateral optic neuropathy and ophthalmoplegia together caused by spheno-ethmoidal mucocele. We present such a rare case of spheno-ethmoidal mucocele causing bilateral optic neuropathy and unilateral sixth nerve palsy who had postsurgery, unilateral good vision recovery, and complete resolution of sixth nerve palsy. PMID:23571243

  7. Spheniodal mucocele causing bilateral optic neuropathy and ophthalmoplegia.

    PubMed

    Selvakumar, Ambika; Mahalaxmi, Balasubramanyam; Ananth, V; Gautam, Cugati

    2014-04-01

    Sphenoid sinus mucocele comprises only 2% of all paranasal sinus mucoceles. In literature, there is a case report on sphenoidal mucocele causing bilateral optic neuropathy, with unilateral partial recovery and cranial nerve palsy, but we did not come across any literature with bilateral optic neuropathy and ophthalmoplegia together caused by spheno-ethmoidal mucocele. We present such a rare case of spheno-ethmoidal mucocele causing bilateral optic neuropathy and unilateral sixth nerve palsy who had postsurgery, unilateral good vision recovery, and complete resolution of sixth nerve palsy.

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

    PubMed

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

    2012-03-01

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

  9. 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

  10. 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.

  11. Pediatric peripheral neuropathy in proteus syndrome.

    PubMed

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

    1998-05-01

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

  12. Leber hereditary optic neuropathy in Australia.

    PubMed

    Mackey, D A; Buttery, R G

    1992-08-01

    Leber hereditary optic neuropathy (LHON) presents with sudden onset of visual loss mainly in young adult males. LHON is not uncommon in Australia, accounting for 2% of invalid blind pensions. We have identified 20 unrelated families carrying mitochondrial DNA mutations associated with LHON and 135 of 291 individuals with documented LHON are currently alive in Australia. The mean age of onset of visual loss for males was 26 years and for females 27 years, with a range from six to 65 years. The mean risk of visual loss was 20% for males and 4% for females. There are over 1750 male and female carriers living in Australia who have not yet lost vision; 600 carriers are under 24 years of age. The expected number of new cases of blindness from LHON is three to four per year. PMID:1449769

  13. Idebenone for Leber's hereditary optic neuropathy.

    PubMed

    Gueven, N

    2016-03-01

    Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients. Idebenone (Raxone®) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Thus, commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data. PMID:27186591

  14. Idebenone for Leber's hereditary optic neuropathy.

    PubMed

    Gueven, N

    2016-03-01

    Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients. Idebenone (Raxone®) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Thus, commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data.

  15. Isoniazid induced motor-dominant neuropathy.

    PubMed

    Arsalan, Rabeeya; Sabzwari, Saniya

    2015-10-01

    Isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. A 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid treatment was continued. Her motor weakness gradually improved in a few months, but mild sensory impairment persisted even after two years. There is need for vigilance regarding neurological effects of isoniazid in seemingly low-risk individuals in whom development of symptoms should raise the suspicion about slow acetylator status. Timely therapeutic intervention with high-dose vitamin B6 can reduce the long-term morbidity associated with this easily reversible condition. PMID:26440850

  16. Sciatic nerve injury: a simple and subtle model for investigating many aspects of nervous system damage and recovery.

    PubMed

    Savastano, Luis E; Laurito, Sergio R; Fitt, Marcos R; Rasmussen, Jorge A; Gonzalez Polo, Virginia; Patterson, Sean I

    2014-04-30

    Sciatic nerve injury has been used for over a century to investigate the process of nerve damage, to assess the absolute and relative capacity of the central and peripheral nervous systems to recover after axotomy, and to understand the development of chronic pain in many pathologies. Here we provide a historical review of the contributions of this experimental model to our current understanding of fundamental questions in the neurosciences, and an assessment of its continuing capacity to address these and future problems. We describe the different degrees of nerve injury - neurapraxia, axonotmesis, neurotmesis - together with the consequences of selective damage to the different functional and anatomic components of this nerve. The varied techniques used to model different degrees of nerve injury and their relationship to the development of neuropathic pain states are considered. We also provide a detailed anatomical description of the sciatic nerve from the spinal cord to the peripheral branches in the leg. A standardized protocol for carrying out sciatic nerve axotomy is proposed, with guides to assist in the accurate and reliable dissection of the peripheral and central branches of the nerve. Functional, histological, and biochemical criteria for the validation of the injury are described. Thus, this paper provides a review of the principal features of sciatic nerve injury, presents detailed neuroanatomical descriptions of the rat's inferior limb and spine, compares different modes of injury, offers material for training purposes, and summarizes the immediate and longterm consequences of damage to the sciatic nerve.

  17. 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

  18. Local Effect of Heparin Binding Neurotrophic Factor Combined With Chitosan Entubulization on Sciatic Nerve Repair in Rats

    PubMed Central

    Mehrshad, Ali; Seddighnia, Ashkan; Shadabi, Mohammadreza; Najafpour, Alireza; Mohammadi, Rahim

    2016-01-01

    Objective: To assess the effect of on sciatic nerve regeneration in animal model of rat. Methods: Seventy-five male Wistar rats were divided into five experimental groups randomly (each group containing 15 animals): Sham operation group (SHAM), autograft group (AUTO), transected control (TC), chitosan conduit (CHIT) and heparin binding neurotrophic factor treated group (CHIT/HBNF). In AUTO group a segment of sciatic nerve was transected and reimplanted reversely. In SHAM group sciatic nerve was exposed and manipulated. In transected group left sciatic nerve was transected and stumps were fixed in adjacent muscle (TC). In treatment group defect was bridged using a chitosan conduit (CHIT) filled with 10 µL HBNF (CHIT/HBNF). Each group was subdivided into four subgroups of five animals each and nerve fibers were studied in a 12-week period. Results: Behavioral, functional, biomechanical, electrophysiological and gastrocnemius muscle mass findings and morphometric indices confirmed faster recovery of regenerated axons in treatment group than in CHIT group (P=0.001). Immunohistochemical reactions to S-100 in treatment group were more positive than that in CHIT group. Conclusion: Local administration of improved functional recovery and morphometric indices of sciatic nerve. It could be considered as an effective treatment for peripheral nerve repair in practice. PMID:27331064

  19. Sciatic nerve injury: a simple and subtle model for investigating many aspects of nervous system damage and recovery.

    PubMed

    Savastano, Luis E; Laurito, Sergio R; Fitt, Marcos R; Rasmussen, Jorge A; Gonzalez Polo, Virginia; Patterson, Sean I

    2014-04-30

    Sciatic nerve injury has been used for over a century to investigate the process of nerve damage, to assess the absolute and relative capacity of the central and peripheral nervous systems to recover after axotomy, and to understand the development of chronic pain in many pathologies. Here we provide a historical review of the contributions of this experimental model to our current understanding of fundamental questions in the neurosciences, and an assessment of its continuing capacity to address these and future problems. We describe the different degrees of nerve injury - neurapraxia, axonotmesis, neurotmesis - together with the consequences of selective damage to the different functional and anatomic components of this nerve. The varied techniques used to model different degrees of nerve injury and their relationship to the development of neuropathic pain states are considered. We also provide a detailed anatomical description of the sciatic nerve from the spinal cord to the peripheral branches in the leg. A standardized protocol for carrying out sciatic nerve axotomy is proposed, with guides to assist in the accurate and reliable dissection of the peripheral and central branches of the nerve. Functional, histological, and biochemical criteria for the validation of the injury are described. Thus, this paper provides a review of the principal features of sciatic nerve injury, presents detailed neuroanatomical descriptions of the rat's inferior limb and spine, compares different modes of injury, offers material for training purposes, and summarizes the immediate and longterm consequences of damage to the sciatic nerve. PMID:24487015

  20. Intravenous immunoglobulins in peripheral neuropathy associated with vasculitis

    PubMed Central

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

    2003-01-01

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

  1. The debut of a rational treatment for an inherited neuropathy?

    PubMed Central

    Scherer, Steven S.

    2011-01-01

    Hereditary neuropathies are common neurological conditions characterized by progressive loss of motor and/or sensory function. There are no effective treatments. Among the many causes of hereditary neuropathies are dominant mutations in serine palmitoyltransferase, long chain base subunit 1 (SPTLC1), which cause hereditary sensory and autonomic neuropathy type 1 (HSAN1). By incorporating l-alanine in place of l-serine, the mutant HSAN1–associated serine palmitoyltransferase generates deoxysphingolipids, which are thought to be neurotoxic. In this issue of the JCI, Garofalo and colleagues report that oral l-serine reverses the accumulation of deoxysphingolipids in humans with HSAN1 and in a transgenic mouse model. As oral l-serine reduces the severity of neuropathy in the mouse model of HSAN1, these data suggest a rational candidate therapy for this devastating condition. PMID:22045569

  2. Familial Idiopathic Cranial Neuropathy in a Chinese Family.

    PubMed

    Zhang, Li; Liang, Jianfeng; Yu, Yanbing

    2016-01-01

    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. PMID:27161475

  3. 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

  4. The debut of a rational treatment for an inherited neuropathy?

    PubMed

    Scherer, Steven S

    2011-12-01

    Hereditary neuropathies are common neurological conditions characterized by progressive loss of motor and/or sensory function. There are no effective treatments. Among the many causes of hereditary neuropathies are dominant mutations in serine palmitoyltransferase, long chain base subunit 1 (SPTLC1), which cause hereditary sensory and autonomic neuropathy type 1 (HSAN1). By incorporating L-alanine in place of L-serine, the mutant HSAN1–associated serine palmitoyltransferase generates deoxysphingolipids, which are thought to be neurotoxic. In this issue of the JCI, Garofalo and colleagues report that oral L-serine reverses the accumulation of deoxysphingolipids in humans with HSAN1 and in a transgenic mouse model. As oral L-serine reduces the severity of neuropathy in the mouse model of HSAN1, these data suggest a rational candidate therapy for this devastating condition. PMID:22045569

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

    PubMed Central

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

    2010-01-01

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

  6. Pathogenesis and treatment of immune-mediated neuropathies.

    PubMed

    Lehmann, Helmar C; Meyer Zu Horste, Gerd; Kieseier, Bernd C; Hartung, Hans-Peter

    2009-07-01

    Immune-mediated neuropathies represent a heterogeneous spectrum of peripheral nerve disorders that can be classified according to time course, predominant involvement of motor/sensory fibers, distribution of deficits and paraclinical parameters such as electrophysiology and serum antibodies. In the last few years, significant advances have been achieved in elucidating underlying pathomechanisms, which made it possible to identify potential therapeutic targets. In this review, we discuss the latest development in pathogenesis and treatment of immune-mediated neuropathies.

  7. 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

  8. Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation.

    PubMed

    Komirishetty, Prashanth; Areti, Aparna; Sistla, Ramakrishna; Kumar, Ashutosh

    2016-08-01

    Neuropathic pain is initiated or caused due to the primary lesion or dysfunction in the nervous system and is proposed to be linked to a cascade of events including excitotoxicity, oxidative stress, neuroinflammation and apoptosis. Oxidative/nitrosative stress aggravates the neuroinflammation and neurodegeneration through poly (ADP) ribose polymerase (PARP) overactivation. Hence, the present study investigated the antioxidant and anti-inflammatory effects of the phytoconstituent; morin in chronic constriction injury (CCI) induced neuropathy. Neuropathic pain was induced by chronic constriction of the left sciatic nerve in rats, and the effect of morin (15 and 30 mg/kg, p.o.) was evaluated by measuring behavioural and biochemical changes. Mechanical, chemical and thermal stimuli confirmed the CCI-induced neuropathic pain and treatment with morin significantly improved these behavioural deficits and improved the sciatic functional index by the 14th day after CCI induction. After 14 days of CCI induction, oxidative/nitrosative stress and inflammatory markers were elevated in rat lumbar spinal cord. Oxidative stress induced PARP overactivation resulted in depleted levels of ATP and elevated levels of poly (ADP) ribose (PAR). Treatment with morin reduced the levels of nitrites, restored glutathione levels and abrogated the oxidant induced DNA damage. It also mitigated the increased levels of TNF-α and IL-6. Protein expression studies confirmed the PARP inhibition and anti-inflammatory activity of morin. Findings of this study suggest that morin, by virtue of its antioxidant properties, limited PARP overactivation and neuroinflammation and protected against CCI induced functional, behavioural and biochemical deficits. PMID:27084773

  9. Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation.

    PubMed

    Komirishetty, Prashanth; Areti, Aparna; Sistla, Ramakrishna; Kumar, Ashutosh

    2016-08-01

    Neuropathic pain is initiated or caused due to the primary lesion or dysfunction in the nervous system and is proposed to be linked to a cascade of events including excitotoxicity, oxidative stress, neuroinflammation and apoptosis. Oxidative/nitrosative stress aggravates the neuroinflammation and neurodegeneration through poly (ADP) ribose polymerase (PARP) overactivation. Hence, the present study investigated the antioxidant and anti-inflammatory effects of the phytoconstituent; morin in chronic constriction injury (CCI) induced neuropathy. Neuropathic pain was induced by chronic constriction of the left sciatic nerve in rats, and the effect of morin (15 and 30 mg/kg, p.o.) was evaluated by measuring behavioural and biochemical changes. Mechanical, chemical and thermal stimuli confirmed the CCI-induced neuropathic pain and treatment with morin significantly improved these behavioural deficits and improved the sciatic functional index by the 14th day after CCI induction. After 14 days of CCI induction, oxidative/nitrosative stress and inflammatory markers were elevated in rat lumbar spinal cord. Oxidative stress induced PARP overactivation resulted in depleted levels of ATP and elevated levels of poly (ADP) ribose (PAR). Treatment with morin reduced the levels of nitrites, restored glutathione levels and abrogated the oxidant induced DNA damage. It also mitigated the increased levels of TNF-α and IL-6. Protein expression studies confirmed the PARP inhibition and anti-inflammatory activity of morin. Findings of this study suggest that morin, by virtue of its antioxidant properties, limited PARP overactivation and neuroinflammation and protected against CCI induced functional, behavioural and biochemical deficits.

  10. Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

    PubMed Central

    Jin, Heung Yong; Baek, Hong Sun

    2015-01-01

    Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN). Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed. PMID:26706915

  11. Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy.

    PubMed

    Jin, Heung Yong; Baek, Hong Sun; Park, Tae Sun

    2015-12-01

    Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN). Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed. PMID:26706915

  12. 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

  13. 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.

  14. 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

  15. Acetyl salicylic acid locally enhances functional recovery after sciatic nerve transection in rat.

    PubMed

    Mohammadi, Rahim; Amini, Keyvan; Abdollahi-Pirbazari, Mehdi; Yousefi, Alireza

    2013-01-01

    Local effect of acetyl salicylic acid (ASA) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model. Forty-five male healthy White Wistar rats were divided into three experimental groups (n = 15), randomly: Sham-operation (SHAM), control (SIL), and ASA-treated (SIL/ASA) groups. In SHAM group after anesthesia left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis the muscle was sutured. In SIL group the left sciatic nerve was exposed the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone tube and filled with 10 μl phosphate buffered solution. In SIL/ASA group defect was bridged using a silicone tube filled with 10 μl acetyl salisylic acid (0.1 mg/ml). Each group was subdivided into three subgroups of five animals each and were studied 4, 8, and 12 weeks after surgery. Data were analyzed statistically by factorial analysis of variance (ANOVA) and the Bonferroni test for pair-wise comparisons. Functional study confirmed faster and better recovery of regenerated axons in SIL/ASA than in SIL group (p < 0.05). Gastrocnemius muscle mass in SIL/ASA was significantly more than in SIL group. Morphometric indices of regenerated fibers showed that the number and diameter of the myelinated fibers in SIL/ASA were significantly higher than in control group. In immuohistochemistry, location of reactions to S-100 in SIL/ASA was clearly more positive than in SIL group. Response to local treatment of ASA demonstrates that it influences and improves functional recovery of peripheral nerve regeneration.

  16. 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.

  17. (-)-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. PMID:23313191

  18. [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.

  19. 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.

  20. Cryoanalgesia. Ultrastructural study on cryolytic lesion of sciatic nerve in rat and rabbit.

    PubMed

    Fasano, V A; Peirone, S M; Zeme, S; Filippi, M; Broggi, G; de Mattei, M; Sguazzi, A

    1987-01-01

    The sciatic nerve was exposed to cryoinjury at different freezing patterns in albino rats and rabbits and the frozen nerves were serially examined with electron microscopy from the time of cryolitic lesion (--60 degrees C for 3 minutes) for up to 28 days. The cryolesion was characterized by a total degeneration of the myelin fibers, while non-myelin fibers and vessels seemed less affected. Regeneration began 8 days after cryolysis. A peculiar pattern was the absence of Schwann cells, while the basal membrane around regenerating axons remained intact. The hypothesis that the basal membrane might play a role is discussed. PMID:2823542

  1. Sequential imaging of intraneural sciatic nerve endometriosis provides insight into symptoms of cyclical sciatica.

    PubMed

    Capek, Stepan; Amrami, Kimberly K; Howe, Benjamin M; Collins, Mark S; Sandroni, Paola; Cheville, John C; Spinner, Robert J

    2016-03-01

    Endometriosis of the nerve often remains an elusive diagnosis. We report the first case of intraneural lumbosacral plexus endometriosis with sequential imaging at different phases of the menstrual cycle: during the luteal phase and menstruation. Compared to the first examination, the examination performed during the patient's period revealed the lumbosacral plexus larger and hyperintense on T2-weighted imaging. The intraneural endometriosis cyst was also larger and showed recent hemorrhage. Additionally, this case represents another example of perineural spread of endometriosis from the uterus to the lumbosacral plexus along the autonomic nerves and then distally to the sciatic nerve and proximally to the spinal nerves.

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

    PubMed

    Kelly, John J

    2004-01-01

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

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

    PubMed Central

    Kamate, Mahesh; Ramakrishna, Shashikala; Kambali, Shweta; Mahadevan, Anita

    2014-01-01

    Giant axonal neuropathy (GAN) is a rare hereditary neurodegenerative disorder characterised by accumulation of excess neurofilaments in the axons of peripheral and central nervous systems, which hampers signal transmission. It usually manifests in infancy and early childhood and is slowly progressive. Those affected with GAN have characteristic curly kinky hair, everted feet and a crouched gait, which suggest the diagnosis in most cases. We describe twin children who presented with difficulty in walking and an abnormal gait since they began walking; clinical clues such as hair changes led us to the final diagnosis. PMID:25216920

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

    PubMed Central

    Ferrari, Luiz F.; Levine, Jon D.

    2010-01-01

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

  5. Inhibition of nerve conduction by electromagnetic induction of the frog sciatic nerve-gastrocnemius muscle preparation.

    PubMed

    Wali, F A; Brain, A I

    1989-01-01

    The effect of electromagnetic induction (EMI) on impulse conduction and muscle contraction was studied in isolated sciatic nerve-gastrocnemius muscle preparation of the frog. Electrical stimulation (ES) of the sciatic nerve, at 0.5 Hz with 0.6 V (supramaximal) and 1-ms pulse duration, produced twitch contractions (3.5 +/- 0.4 g tension, mean +/- S.E., n = 8 frogs), which were reduced or blocked by EMI, applied to the nerve via an induction coil, from a d.c. source of 1.5-4 V, at a frequency of 100 min-1, for 2- to 4-min duration. Recovery of the blocked twitches was obtained within 4-5 min, after the cessation of the EMI and washing out the preparation in Ringer solution. The inhibition of the twitch tension by EMI was compared to that produced by an effective concentration of a local anaesthetic, lignocaine (1 microM), which is known to block conduction, by blocking ionic fluxes across the nerve membrane. It is possible that EMI also interferes with the ionic fluxes, and in prolonged duration, may produce changes in the myelin sheath (or the Schwann cells) of the nerve membrane. A comparison of ES with EMI was made, and it was concluded that EMI inhibited electrically induced neuromuscular transmission at the frog neuromuscular junction.

  6. An immunohistochemical study of the sciatic nerve in a rat knee immobilization model

    PubMed Central

    Yoshida, Shinya; Matsuzaki, Taro; Hoso, Masahiro

    2016-01-01

    [Purpose] This study was performed to immunohistochemically evaluate changes in the periphery of the sciatic nerve in a rat model of knee immobilization, and to assess the effects of range of motion exercise. [Subjects and Methods] Twenty-one male rats were divided randomly into three groups: control (C), immobilized (I), and exercise (E group). Rats in the I and E groups had the right knee joint immobilized for 2 weeks. In the E group, range of motion exercise was also performed. After the experimental period, the periphery of the sciatic nerve was immunohistochemically observed. [Results] Immunohistochemical staining revealed that the myelin sheath and the perineurium in all groups were laminin positive. In the C and E groups, all rats showed normal staining. In contrast, 4 rats in the I group exhibited weak labeling. [Conclusion] Our results suggest that immobilization alters the perineurium at a molecular level and the range of motion exercise is essential for maintaining the environment of the perineurium. PMID:27190437

  7. Postoperative sciatic and femoral or saphenous nerve blockade for lower extremity surgery in anesthetized adults

    PubMed Central

    Lollo, Loreto; Bhananker, Sanjay; Stogicza, Agnes

    2015-01-01

    Background: Guidelines warn of increased risks of injury when placing regional nerve blocks in the anesthetized adult but complications occurred in patients that received neither sedation nor local anesthetic. This restriction of nerve block administration places vulnerable categories of patients at risk of severe opioid induced side effects. Patient and operative technical factors can preclude use of preoperative regional anesthesia. The purpose of this study was to assess complications following sciatic popliteal and femoral or saphenous nerve blockade administered to anesthetized adult patients following foot and ankle surgery. Materials and Methods: Postoperative patients administered general anesthesia received popliteal sciatic nerve blockade and either femoral or saphenous nerve blockade if operative procedures included medial incisions. Nerve blocks were placed with nerve stimulator or ultrasound guidance. A continuous nerve catheter was inserted if hospital admission was over 24 hours. Opioid analgesic supplementation was administered for inadequate pain relief. Postoperative pain scores and total analgesic requirements for 24 hours were recorded. Nerve block related complications were monitored for during the hospital admission and at follow up surgical clinic evaluation. Results: 190 anesthetized adult patients were administered 357 nerve blocks. No major nerve injury or deficit was reported. One patient had numbness in the toes not ascribed to a specific nerve of the lower extremity. Perioperative opioid dose differences were noted between male and female and between opioid naïve and tolerant patients. PMID:26807391

  8. Gabapentin attenuates neuropathic pain and improves nerve myelination after chronic sciatic constriction in rats.

    PubMed

    Câmara, Carlos C; Araújo, Celina V; de Sousa, Kalina Kelma Oliveira; Brito, Gerly A C; Vale, Mariana L; Raposo, Ramon da Silva; Mendonça, Fabiana Evaristo; Mietto, Bruno S; Martinez, Ana Maria B; Oriá, Reinaldo B

    2015-10-21

    Gabapentin (GBP) is an anti-convulsive drug often used as analgesic to control neuropathic pain. This study aimed at evaluating oral GBP treatment (30, 60, 120 mg/kg, 60 min prior to chronic constriction of the sciatic nerve (CCSN) along 15-day treatment post-injury, 12 h/12 h) by monitoring spontaneous and induced-pain behaviors in Wistar rats on 5th and 15th days post-injury during early neuropathic events. CCSN animals receiving saline were used as controls. Another aim of this study was to evaluate GBP effects on myelin basic protein (MBP) on the 5th and 15th days post-injury and nerve morphology by transmission electron microscopy to address nerve regeneration. On the 5th and 15th days, GBP (60 mg/kg) reduced neuropathic pain behaviors (scratching and biting) in the ipsilateral paw and alleviated mechanical allodynia in comparison with the neuropathic saline group. GBP significantly increased climbing and rearing behaviors in CCSN and CCSN-free animals suggesting increased motor activity rather than sedation. We found three-fold significant increase in MBP expression by western blots on the 15th day when compared to controls. In addition, GPB (60 mg/kg) improved nerve axonal, fiber and myelin area 15 days post-surgery. In conclusion, GBP alleviated mechanical and thermal allodynia and spontaneous pain-related behaviors and improved later nerve morphology. Our findings suggest that GBP improve nerve remyelination after chronic constriction of the sciatic nerve.

  9. Sciatic nerve transection modulates oxidative parameters in spinal and supraspinal regions.

    PubMed

    Scheid, Taína; Bosco, Lidiane Dal; Guedes, Renata P; Pavanato, Maria Amália; Belló-Klein, Adriane; Partata, Wania A

    2013-05-01

    Neuropathic pain is a very common dysfunction caused by several types of nerve injury. This condition leads to a variety of pathological changes in central nervous system regions related to pain transmission. It has been demonstrated that nociception is modulated by reactive oxidative species and treatments with antioxidant compounds produce antinociceptive effects. Thus, the aim of the present study was to investigate oxidative parameters in spinal and supraspinal regions following sciatic nerve transection (SNT). In behavioral assessments, animals showed mechanical allodynia and a significant functional impairment following SNT, measured by von Frey hairs test and sciatic functional index, respectively. Superoxide dismutase activity was increased 3 and 7 days following SNT in cerebral cortex and brainstem. Catalase activity was also increased in cerebral cortex 3 days after SNT. Ascorbic acid levels were decreased 7 days in the spinal cord only in SNT group. We also showed an increase in lipid peroxidation in cerebral cortex and brainstem 3 days after surgery in SNT and sham groups. These results showed that supraspinal regions also exhibit changes in antioxidant activity after SNT and demonstrate an intricate relationship among antioxidant defenses in different regions of the neuro axis related to pain transmission. PMID:23423532

  10. 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. PMID:23060343

  11. The effect of ubiquinone on functional recovery and morphometric indices of sciatic nerve regeneration

    PubMed Central

    Moradi, Z; Azizi, S; Hobbenaghi, R

    2014-01-01

    A common cause of peripheral nerve injury is trauma. The positive effect of antioxidants on the improvement of nerve regeneration has currently become a focus of attention. In this experiment, the effect of intraperitoneal administration of ubiquinone (CoQ10) on an acute experimentally sciatic nerve crush was studied in a rat model. Forty-five male Wistar rats, weighing between 160-180 g were used. The rats were randomly divided into two experimental groups (n=20). Each group was further subdivided into four subgroups of five animals each. Functional studies confirmed the faster recovery of regenerated axons in the treatment group compared to the un-treated group (P<0.05). Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers to be significantly higher in the treatment group than the un-treated group (P<0.05). Intraperitoneal administration of CoQ10 (10 mg/kg/day) in the early inflammatory stage of sciatic nerve crush was found to improve nerve regeneration. PMID:27175137

  12. Functioning of patients with multifocal motor neuropathy.

    PubMed

    Erdmann, Peter G; Lindeman, Eline; Cats, Elisabeth A; van den Berg, Leonard H

    2010-06-01

    Patients with multifocal motor neuropathy (MMN) have slowly progressive, predominantly distal asymmetric limb weakness without sensory loss. While previous studies have investigated the impact of MMN on body functions and structures, relatively little is known about the impact of patients' weakness on daily functioning. The aim of the present cross-sectional study, involving 47 patients with MMN, was to evaluate determinants of patients' functioning. Most patients showed not only muscle weakness but also fatigue, limited dexterity, and limited walking ability. Regression models showed that age, hand aids, and muscle strength scores together explained 54% of the variance in dexterity scores, which in turn explained 8% of the variance in patients' scores for autonomy indoors. Age, the use of walking aids, and muscle strength scores together explained 58% of the variance in walking ability scores, which in turn explained 18% of the variance in patients' scores for autonomy indoors and 7% of the variance in patients' scores for autonomy outdoors. Assessment of determinants of patient functioning may make it possible to tailor interventions to address these aspects and thereby improve patients' functioning in daily life. PMID:20626774

  13. Chronic peripheral neuropathy responsive to rituximab.

    PubMed

    Kelly, John J

    2006-01-01

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

  14. Traumatic Optic Neuropathy – A Conundrum

    PubMed Central

    Selvaraj, Vinoth Kanna; Devanathan, Vasudevan

    2016-01-01

    Visual impairment following head injury may be an enigma especially if the onset of symptoms were to be few days after the actual trauma and the bias arising out of the initial normal ophthalmological examination is not neutralised by unbiased repeated formal clinical evaluation aided with electrophysiology. We report and discuss here a 32-year-old lady with delayed onset of indirect traumatic visual loss with anaemia who failed to improve after blood transfusion but improved immediately following steroid therapy seven days after trauma. Though steroids have not been shown to have a significant contribution on outcomes following Traumatic optic neuropathy, this report rekindles its role in delayed progressive visual loss following head trauma and the need to re-analyse the role of steroids in patients with delayed progressive visual disturbance following head injury excluding those with acute onset symptoms in view of different pathologies in both these presentations. This paper also highlights potential mechanisms for the two major types of presentation. PMID:27134913

  15. Micturition disturbance in acute idiopathic autonomic neuropathy

    PubMed Central

    Sakakibara, R; Uchiyama, T; Asahina, M; Suzuki, A; Yamanishi, T; Hattori, T

    2004-01-01

    Objective: To define the nature of micturition disturbance in patients with acute idiopathic autonomic neuropathy (AIAN). Methods: Micturitional symptoms were observed during hospital admissions and the in outpatient clinics in six patients with clinically definite AIAN (typical form in four, cholinergic variant in one, autonomic-sensory variant in one). Urodynamic studies included medium-fill water cystometry, external sphincter electromyography, and a bethanechol test. Results: Four patients had urinary retention and two had voiding difficulty as the initial presentation. Patients with retention became able to urinate within a week (two to seven days). The major symptoms at the time of urodynamic studies (three weeks to four months after disease onset in most cases) were voiding difficulty and nocturnal frequency. None had urinary incontinence. Complete recovery from the micturition disturbance took from three months to >18 years. The recovery period was shorter in a patient with cholinergic variant, and it was longer in two patients who had a longer duration of initial urinary retention. Micturition disturbance tended to improve earlier than orthostatic hypotension. The major urodynamic abnormalities were detrusor areflexia on voiding (5), denervation supersensitivity to bethanechol (3); low compliance detrusor (1); and impaired bladder sensation (2). None had neurogenic motor unit potentials of the external sphincter muscles. Conclusions: In patients with AIAN, urinary retention and voiding difficulty are common initial presentations. The underlying mechanisms seem to be pre- and postganglionic cholinergic dysfunction with preservation of somatic sphincter function. The bladder problems tend to improve earlier than orthostatic hypotension. PMID:14742606

  16. 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

  17. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    PubMed Central

    Hosseini, Asieh; Abdollahi, Mohammad

    2013-01-01

    Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials. PMID:23738033

  18. Painful Diabetic Neuropathy: Prevention or Suppression?

    PubMed

    Todorovic, S M

    2016-01-01

    Pain-sensing sensory neurons (nociceptors) of the dorsal root ganglia (DRG) and dorsal horn (DH) can become sensitized (hyperexcitable) in response to pathological conditions such as diabetes, which in turn may lead to the development of painful peripheral diabetic neuropathy (PDN). Because of incomplete knowledge about the mechanisms underlying painful PDN, current treatment for painful PDN has been limited to somewhat nonspecific systemic drugs that have significant side effects or potential for abuse. Recent studies have established that several ion channels in DRG and DH neurons are dysregulated and make a previously unrecognized contribution to sensitization of pain responses by enhancing excitability of nociceptors in animal models of type 1 and type 2 PDN. Furthermore, it has been reported that targeting posttranslational modification of nociceptive ion channels such as glycosylation and methylglyoxal metabolism can completely reverse mechanical and thermal hyperalgesia in diabetic animals with PDN in vivo. Understanding details of posttranslational regulation of nociceptive channel activity may facilitate development of novel therapies for treatment of painful PDN. We argue that pharmacological targeting of the specific pathogenic mechanism rather than of the channel per se may cause fewer side effects and reduce the potential for drug abuse in patients with diabetes. PMID:27133151

  19. [Designation criteria for Leber's hereditary optic neuropathy].

    PubMed

    Nakamura, Makoto; Mimura, Osamu; Wakakura, Masato; Inatani, Masaru; Nakazawa, Toru; Shiraga, Fumio

    2015-05-01

    Designation criteria for Leber's hereditary optic neuropathy (LHON) have been established by a working group for retino-choroidal and optic atrophy funded by the Ministry of Health, Labor, and Welfare (MHLW) of Japan in collaboration with the Japanese Neuro-ophthalmology Society. The criteria are composed of three major symptoms and three ancillary test findings. According to the number and the combination of these symptoms and findings, subjects are classified into definite, probable, and possible LHON cases and asymptomatic carriers. The major symptoms include bilateral involvement with a time-lag, a papillomacular bundle atrophy, both characteristic optic disc findings at the acute phase. In the ancillary testings, mitochondrial DNA mutations specific for LHON are detailed with a table listing the mutation loci being attached. To enhance readers' understanding of description of the major symptoms and ancillary test findings, explanatory remarks on 11 parameters are supplemented. The establishment of the criteria facilitates epidemiological survey of LHON by MHLW and contributes to improvement of welfare for patients with LHON in Japan.

  20. 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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Santhi, Datuk Puvanarajah; Mohd Hanip, Rafia

    2014-01-01

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

  3. Mutation in FAM134B causing severe hereditary sensory neuropathy

    PubMed Central

    Murphy, Sinead M; Davidson, Gabrielle L; Brandner, Sebastian; Houlden, Henry; Reilly, Mary M

    2013-01-01

    The hereditary sensory and autonomic neuropathies (HSAN) are rare inherited neuropathies presenting with sensory loss and complications, including ulcers, infections, osteomyelitis and amputations. Usually, sensory symptoms predominate although motor involvement can occur. Autonomic features may be minimal (then hereditary sensory neuropathy, HSN, is preferred). HSAN has been classified into five subtypes depending on clinical presentation.1 Hereditary sensory and autonomic neuropathy II (HSANII or HSNII) is an early onset, autosomal recessive sensory neuropathy with ulcero-mutilating complications due to mutations in the HSN2 isoform of the WNK1 gene.2 Recently, a similar phenotype was described in a Saudi-Arabian family, and a homozygous nonsense mutation found in a new gene, FAM134B (family with sequence similarity 134, member B), encoding a newly identified Golgi protein. The index case in this family was initially thought to have leprosy. Three additional families (out of 75 patients) with similar phenotypes were found to have homozygous loss of function mutations in FAM134B.3 Here, we report the clinical and pathological findings in a further patient with HSNII due to a homozygous mutation in FAM134B. PMID:21115472

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

    PubMed

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

    2015-01-01

    The skin's rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to investigate whether the skin rewarming rate in diabetic rats is related to microvascular changes and whether this is accompanied by changes observed in classical diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared thermography was used to assess the rewarming rate after cold exposure on the plantar skin of STZ diabetic rats' hind paws. Peripheral neuropathy was determined by the density of intra-epidermal nerve fibers (IENFs), mechanical sensitivity, and electrophysiological recordings. Data were obtained in diabetic rats at four, six, and eight weeks after the induction of diabetes and in controls. Four weeks after the induction of diabetes, a delayed rewarming rate, decreased skin blood flow and decreased density of IENFs were observed. However, the mechanical hyposensitivity and decreased motor nerve conduction velocity (MNCV) developed 6 and 8 weeks after the induction of diabetes. Our study shows that the skin rewarming rate is related to microvascular changes in diabetic rats. Moreover, the skin rewarming rate is a non-invasive method that provides more information for an earlier diagnosis of peripheral neuropathy than the classical monofilament test and MNCV in STZ induced diabetic rats.

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

    PubMed

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

    2016-01-01

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

  6. 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

  7. 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

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

    PubMed Central

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

    1997-01-01

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

  9. Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db-/db- mouse, a type 2 diabetes model.

    PubMed

    Shi, Tie-Jun Sten; Zhang, Ming-Dong; Zeberg, Hugo; Nilsson, Johanna; Grünler, Jacob; Liu, Su-Xing; Xiang, Qiong; Persson, Jonas; Fried, Kaj J; Catrina, Sergiu Bogdan; Watanabe, Masahiko; Arhem, Peter; Brismar, Kerstin; Hökfelt, Tomas G M

    2013-01-01

    Diabetic peripheral neuropathy (DPN) is the most common complication in both type 1 and type 2 diabetes. Here we studied some phenotypic features of a well-established animal model of type 2 diabetes, the leptin receptor-deficient db(-)/db(-) mouse, and also the effect of long-term (6 mo) treatment with coenzyme Q10 (CoQ10), an endogenous antioxidant. Diabetic mice at 8 mo of age exhibited loss of sensation, hypoalgesia (an increase in mechanical threshold), and decreases in mechanical hyperalgesia, cold allodynia, and sciatic nerve conduction velocity. All these changes were virtually completely absent after the 6-mo, daily CoQ10 treatment in db(-)/db(-) mice when started at 7 wk of age. There was a 33% neuronal loss in the lumbar 5 dorsal root ganglia (DRGs) of the db(-)/db(-) mouse versus controls at 8 mo of age, which was significantly attenuated by CoQ10. There was no difference in neuron number in 5/6-wk-old mice between diabetic and control mice. We observed a strong down-regulation of phospholipase C (PLC) β3 in the DRGs of diabetic mice at 8 mo of age, a key molecule in pain signaling, and this effect was also blocked by the 6-mo CoQ10 treatment. Many of the phenotypic, neurochemical regulations encountered in lumbar DRGs in standard models of peripheral nerve injury were not observed in diabetic mice at 8 mo of age. These results suggest that reactive oxygen species and reduced PLCβ3 expression may contribute to the sensory deficits in the late-stage diabetic db(-)/db(-) mouse, and that early long-term administration of the antioxidant CoQ10 may represent a promising therapeutic strategy for type 2 diabetes neuropathy. PMID:23267110

  10. Curcumin upregulates S100 expression and improves regeneration of the sciatic nerve following its complete amputation in mice.

    PubMed

    Liu, Guo-Min; Xu, Kun; Li, Juan; Luo, Yun-Gang

    2016-08-01

    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

  11. 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

  12. 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.

  13. 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...

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

    PubMed

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

    2014-06-01

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

  15. Auditory Neuropathy/Dys-synchrony and Its Perceptual Consequences

    PubMed Central

    Rance, Gary

    2005-01-01

    Auditory neuropathy/dys-synchrony is a form of hearing impairment in which cochlear outer hair cell function is spared but neural transmission in the auditory pathway is disordered. This condition, or group of conditions with a common physiologic profile, accounts for approximately 7% of permanent childhood hearing loss and a significant (but as yet undetermined) proportion of adult impairment. This paper presents an overview of the mechanisms underlying auditory neuropathy/dys-synchrony-type hearing loss and the clinical profile for affected patients. In particular it examines the perceptual consequences of auditory neuropathy/dys-synchrony, which are quite different from those associated with sensorineural hearing loss, and considers currently available, and future management options. PMID:15920648

  16. 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.

  17. 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. PMID:20083290

  18. Image analysis software for following progression of peripheral neuropathy

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  19. Periaxin mutations cause recessive Dejerine-Sottas neuropathy.

    PubMed

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

    2001-02-01

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

  20. Is there a relationship between oral health and diabetic neuropathy?

    PubMed

    Borgnakke, Wenche S; Anderson, Patricia F; Shannon, Carol; Jivanescu, Anca

    2015-11-01

    Diabetic neuropathy is the most common microvascular complication of diabetes mellitus with high morbidity and mortality, and low quality of life. It has a broad spectrum of clinical forms, although distal symmetrical polyneuropathy is the most prevalent. Several oral complications including burning mouth syndrome, dry mouth, and impairment of the senses taste and smell are less-known manifestations of diabetic neuropathy and often overlooked. Periodontitis, tooth loss, and temporomandibular joint dysfunction may be also present in these patients and are equally debilitating. Periodontitis was declared the sixth complication of diabetes in 1993 and may contribute to poor glucose control. Hence, periodontitis and diabetes mutually and adversely affect each other. This review summarizes the available body of scientific literature that discusses oral manifestations in patients with diabetic neuropathy and identifies important areas where more research is needed. PMID:26374570

  1. Glaucoma progression associated with Leber's hereditary optic neuropathy.

    PubMed

    Nucci, Carlo; Martucci, Alessio; Mancino, Raffaele; Cerulli, Luciano

    2013-02-01

    The purpose of this article is to describe a case of open-angle glaucoma progression associated with Leber's hereditary optic neuropathy. Single case analysis method is used. A 53-year-old woman with a previous diagnosis of glaucoma presented with progressive visual field loss. Complete ophthalmological examination and blood tests were negative for other concomitant diseases. Genetic counseling revealed mitochondrial DNA mutation compatible with the diagnosis of Leber's hereditary optic neuropathy. In conclusion, the case describes the concomitant occurrence of open-angle glaucoma and Leber's optic neuropathy. We hypothesize that the two diseases may have a cumulative effect on oxidative stress and retinal ganglion cell death with the consequent rapid progression of visual impairment. Screening for mitochondrial DNA mutations may be requested in patients with glaucoma who, despite pharmacologically controlled intraocular pressure, show rapid progression of the disease.

  2. 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. PMID:26323349

  3. 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. PMID:27288016

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

    PubMed

    Hessl, S M; Berman, E

    1982-05-01

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

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

    PubMed

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

    1985-01-01

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

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

    PubMed

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

    2015-06-01

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

  7. Deficiency of thiosulphate sulphurtransferase (rhodanese) in Leber's hereditary optic neuropathy.

    PubMed Central

    Poole, C J; Kind, P R

    1986-01-01

    Leber's hereditary optic neuropathy is a rare cause of progressive visual failure. Its cause is unknown, but one hypothesis is that patients have a defect in the detoxication of cyanide. One of the enzymes used in this detoxication is thiosulphate sulphurtransferase (rhodanese). The activity of this enzyme was measured in the rectal mucosa of a group of subjects with Leber's hereditary optic neuropathy, and it was found to be considerably reduced compared with that in a group of controls (p less than 0.001). This finding supports the hypothesis of an inborn error of cyanide detoxication in this condition. PMID:3085790

  8. Microvascular dysfunction in the context of diabetic neuropathy.

    PubMed

    Stirban, Alin

    2014-01-01

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

  9. 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.

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

    PubMed

    Lysandropoulos, Andreas P; Carota, Antonio

    2011-02-01

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

  11. [Cardiac autonomic neuropathy. Current realities and future outlook].

    PubMed

    Bauduceau, B; Chanudet, X; Mayaudon, H; Chau, N P; Gaillard, J F; Larroque, P; Gautier, D

    1994-01-01

    Cardiac autonomic neuropathy frequently affects Type 1 and Type 2 diabetic patients. This disease is distinguished by visible clinical consequences which can be tragic. It can also worsen a number of degenerative complications. Therefore, cardiac autonomic neuropathy seems to play a deciding role in silent ischaemia and in dysregulations of blood pressure. Clinical explorations continue to be based on the tests validated by Ewing, but the development of simple and reliable techniques seems to be an objective the interest of which cannot escape any clinician.

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

    PubMed Central

    Mazzeo, Anna; Stancanelli, Claudia; Vita, Giuseppe

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    SciTech Connect

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

    1991-07-01

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

  15. Femoral and sciatic nerve block for knee arthroscopy in a patient with acute intermittent porphyria.

    PubMed

    Bosch, L; Villar, T; Latorre, M Y; Pacreu, S

    2016-01-01

    Acute intermittent porphyria is an autosomal dominant disorder that results from a partial deficiency of porphobilinogen deaminase and that causes very severe symptoms. Attacks may be triggered by a series of drugs and by other factors that the anesthesiologist should be aware of in order to reduce morbidity and mortality. Our objective is to review anesthetic considerations in acute intermittent porphyria. We present the case of a patient diagnosed with acute intermittent porphyria who was scheduled for knee arthroscopy. The anesthetic technique used was a femoral and sciatic nerve block under sedation with an infusion of remifentanil. The surgery proceeded without incident and the patient was discharged home after 24h. We consider the use of a peripheral plexus block of the lower limb to have been the safest anesthetic technique for this patient. PMID:27220836

  16. Thermal hyperalgesia after sciatic nerve block in rat is transient and clinically insignificant.

    PubMed

    Janda, Allison; Lydic, Ralph; Welch, Kathleen B; Brummett, Chad M

    2013-01-01

    Ropivacaine has been associated with transient heat hyperalgesia in sciatic nerve blocks in rat. The goal of the present study was to evaluate the hypothesized presence of transient heat hyperalgesia after perineural injection of ropivacaine with a secondary subanalysis of 2 published studies. Paw withdrawal latency was used to assess the duration of sensory blockade and presence of heat hyperalgesia at 210, 240, 270, and 300 minutes and 24 hours after injection. The analysis revealed hyperalgesia at a single time point (240 minutes after injection; mean difference, -0.60 seconds; P = 0.012) that resolved within 30 minutes, and there was no other significant hyperalgesia at other time points. Although statistically significant, the single time point measurement represented only an 11% change from baseline and was no longer present 30 minutes later. These data support the need for a reevaluation of the interpretation that pain can be worsened by perineural ropivacaine injection.

  17. Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury

    NASA Technical Reports Server (NTRS)

    Murashov, A. K.; Ul Haq, I.; Hill, C.; Park, E.; Smith, M.; Wang, X.; Wang, X.; Goldberg, D. J.; Wolgemuth, D. J.

    2001-01-01

    The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.

  18. Addition of Dexamethasone and Buprenorphine to Bupivacaine Sciatic Nerve Block: A Randomized, Controlled Trial

    PubMed Central

    YaDeau, Jacques T.; Paroli, Leonardo; Fields, Kara G.; Kahn, Richard L.; LaSala, Vincent R.; Jules-Elysee, Kethy M.; Kim, David H.; Haskins, Stephen C.; Hedden, Jacob; Goon, Amanda; Roberts, Matthew M.; Levine, David S.

    2015-01-01

    Background and Objectives Sciatic nerve block provides analgesia after foot and ankle surgery, but block duration may be insufficient. We hypothesized that perineural dexamethasone and buprenorphine would reduce pain scores at 24 hours. Methods Ninety patients received ultrasound-guided sciatic (25 mL 0.25% bupivacaine) and adductor canal (10 mL 0.25% bupivacaine) blockade, with random assignment into 3 groups (30 patients per group): control blocks + intravenous dexamethasone (4 mg) (control); control blocks + intravenous buprenorphine (150 mcg) + intravenous dexamethasone (intravenous buprenorphine); nerve blocks containing buprenorphine + dexamethasone (perineural). Patients received mepivacaine neuraxial anesthesia and postoperative oxycodone / acetaminophen, meloxicam, pregabalin, and ondansetron. Patients and assessors were blinded to group assignment. The primary outcome was pain with movement at 24 hours. Results There was no difference in pain with movement at 24 hours (median score 0). However, the perineural group had longer block duration vs control (45.6 vs 30.0 hr). Perineural patients had lower scores for “worst pain” vs control (median 0 vs 2). Both intravenous buprenorphine and perineural groups were less likely to use opioids on the day after surgery, vs control (28.6%, 28.6%, 60.7%, respectively). Nausea after intravenous buprenorphine (but not perineural buprenorphine) was severe, frequent, and bothersome. Conclusions Pain scores were very low at 24 hours after surgery in the context of multimodal analgesia and were not improved by additives. However, perineural buprenorphine and dexamethasone prolonged block duration, reduced the worst pain experienced, and reduced opioid use. Intravenous buprenorphine caused troubling nausea and vomiting. Future research is needed to confirm and extend these observations. PMID:25974277

  19. Naloxone reversible reduction in brain monoamine synthesis following sciatic nerve stimulation.

    PubMed

    Nissbrandt, H; Yao, T; Thorén, P; Svensson, T H

    1982-01-01

    Brain monoaminergic neurons seem to be influenced by endogenous opioid systems as judged from largely indirect evidence. In an attempt to more directly study this interaction, we have analyzed the effect of sciatic nerve stimulation (rectangular pulses, frequency 3 Hz, pulse duration 0.2 msec, current intensity 6-20 times muscle twitch threshold) on the in vivo rate of tyrosine-and tryptophanhydroxylation, respectively, in the rat brain. This stimulation procedure has previously been shown to evoke naloxone reversible pain threshold elevation and a longlasting blood pressure reduction rats, with maximum reached about 1.5 h after stimulation. The formation of DOPA and 5-HTP in various parts of the central nervous system during 30 min after inhibition of L-amino-acid-decarboxylase by NSD 1015 was measured. Two hours after the sciatic nerve stimulation procedure a significant decrease in DOPA formation was obtained in the cerebral cortex and in the spinal cord. This effect was reversed by pretreatment with a high dose of naloxone (15 mg/kg s.c., 10 min before stimulation). A reduction in 5-HTP formation was also obtained in the cerebral cortex, with a concomitant reduction in tryptophan concentration. These effects appeared to be antagonized by naloxone treatment. In the spinal cord there was no change in the 5-HTP accumulation after stimulation, but an increase after stimulation plus naloxone pretreatment was obtained. These data infer that the activity of some central monoamine systems, such as the NA pathways originating in locus coeruleus can be reduced by physiological activation of endogenous opioid systems. This effect of the acupuncture like stimulation procedure may be related to clinically reported actions of acupuncture stimulation, which apart from pain relief include, for example, antagonism of heroin abstinence symptoms.

  20. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    SciTech Connect

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  1. Transient Heat Hyperalgesia During Resolution of Ropivacaine Sciatic Nerve Block in the Rat

    PubMed Central

    Kolarczyk, Lavinia M.; Williams, Brian A.

    2011-01-01

    Background Preliminary studies using perineural sciatic ropivacaine in rat demonstrated unexpected heat hyperalgesia after block resolution. To better characterize the time course relative to mechanical anesthesia-analgesia, we tested the hypothesis that ropivacaine 0.5% leads to transient heat hyperalgesia in rat independent of mechanical nociception. We also evaluated functional toxicity (e.g., long-term hyperalgesia and/or tactile allodynia 2 weeks post-injection). Methods Under surgical exposure, left sciatic nerve block was performed in 2 groups of adult male rats – ropivacaine (200 μL, 5 mg/mL, n=14) versus vehicle (n=11). The efficacy and duration of block was assessed with serial heat, mechanical (Randall-Selitto testing), and tactile (von Frey-like monofilaments) tests; motor-proprioceptive (rotarod) and sedation tests were employed 1 hr and 7 hr post-injection. The presence of nerve injury was assessed by repeating the heat, tactile, and motor tests 12–14 days post-injection. Results Ropivacaine-induced anesthesia was fully manifest at 1 hr post-injection. At 3 hr post-injection, heat hypersensitivity was present in the setting of resolved mechanical analgesia. All behavioral measures returned to baseline by 2 wk post-injection. There was no evidence of (i) behavioral sedation, (ii) persistent changes in heat or mechanical sensitivity, or (iii) persistent changes in proprioceptive-motor function at 12–14 days post-injection. Conclusions Ropivacaine 0.5% induces transient heat hyperalgesia in the setting of resolved mechanical analgesia, further suggestive of modality and/or nociceptive fiber specificity. Whether this finding partially translates to “rebound pain” after patients’ nerve blocks wear off requires further study. PMID:21451438

  2. Topography of Synchronization of Somatosensory Evoked Potentials Elicited by Stimulation of the Sciatic Nerve in Rat

    PubMed Central

    Qu, Xuefeng; Yan, Jiaqing; Li, Xiaoli; Zhang, Peixun; Liu, Xianzeng

    2016-01-01

    Purpose: Traditionally, the topography of somatosensory evoked potentials (SEPs) is generated based on amplitude and latency. However, this operation focuses on the physical morphology and field potential-power, so it suffers from difficulties in performing identification in an objective manner. In this study, measurement of the synchronization of SEPs is proposed as a method to explore brain functional networks as well as the plasticity after peripheral nerve injury. Method: SEPs elicited by unilateral sciatic nerve stimulation in twelve adult male Sprague-Dawley (SD) rats in the normal group were compared with SEPs evoked after unilateral sciatic nerve hemisection in four peripheral nerve injured SD rats. The characterization of synchronized networks from SEPs was conducted using equal-time correlation, correlation matrix analysis, and comparison to randomized surrogate data. Eigenvalues of the correlation matrix were used to identify the clusters of functionally synchronized neuronal activity, and the participation index (PI) was calculated to indicate the involvement of each channel in the cluster. The PI value at the knee point of the PI histogram was used as a threshold to demarcate the cortical boundary. Results: Ten out of the twelve normal rats showed only one synchronized brain network. The remaining two normal rats showed one strong and one weak network. In the peripheral nerve injured group, only one synchronized brain network was found in each rat. In the normal group, all network shapes appear regular and the network is largely contained in the posterior cortex. In the injured group, the network shapes appear irregular, the network extends anteriorly and posteriorly, and the network area is significantly larger. There are considerable individual variations in the shape and location of the network after peripheral nerve injury. Conclusion: The proposed method can detect functional brain networks. Compared to the results of the traditional SEP

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

    PubMed

    Wang, Hongli; Fan, Dongsheng; Zhang, Yingshuang

    2013-12-25

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

  4. Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects: biomechanics and validation of mathematical models

    PubMed Central

    Li, Ya-jun; Zhao, Bao-lin; Lv, Hao-ze; Qin, Zhi-gang; Luo, Min

    2016-01-01

    We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects. PMID:27651781

  5. Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects: biomechanics and validation of mathematical models

    PubMed Central

    Li, Ya-jun; Zhao, Bao-lin; Lv, Hao-ze; Qin, Zhi-gang; Luo, Min

    2016-01-01

    We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.

  6. Combined continuous "3-in-1" and sciatic nerve blocks provide improved postoperative analgesia with no correlation to catheter tip location after unilateral total knee arthroplasty.

    PubMed

    Rajeev, Subramanyam; Batra, Yatindra Kumar; Panda, Nidhi Bidyut; Kumar, Mukesh; Nagi, Onkar Nath

    2007-12-01

    This study assessed the efficacy and duration of postoperative analgesia after continuous sciatic nerve block with and without continuous "3-in-1" block with bupivacaine after unilateral total knee arthroplasty and determined catheter tip correlation with analgesia. Thirty patients were randomized into 2 groups. Results suggested significantly reduced pain and rescue analgesic requirement in combined sciatic and 3-in-1 (group TS) compared to 3-in-1 group alone (group T). The postoperative pain-free interval and satisfaction score was significantly higher in the combined group (P < .05). The percentage of catheters in the ideal position was 53.3% for 3-in-1 and 93.3% for sciatic nerve. In conclusion, continuous sciatic nerve block when added to continuous 3-in-1 block provides a better quality of analgesia with lesser requirements of rescue analgesics without the need for routine radiographic conformation.

  7. Bilateral compressive optic neuropathy secondary to bilateral sphenoethmoidal mucoceles.

    PubMed

    Newton, N; Baratham, G; Sinniah, R; Lim, A

    1989-01-01

    We have presented a rare case of bilateral posterior sphenoethmoidal sinus mucoceles with bilateral compressive optic neuropathy. While the duration of compression was variably present over a 10-month period, there were nevertheless significant improvements in visual acuity of the right eye and visual fields bilaterally following extensive optic nerve decompression.

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

    PubMed

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

    2012-11-01

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

  9. [An Undeniable Case of Optic Neuropathy Due to Cabazitaxel].

    PubMed

    Noguchi, Yusuke; Kawashima, Yugo; Kawara, Hiroko; Kaneko, Masatomo; Nakauchi, Hiroo; Tokuyama, Yoko

    2016-06-01

    Cabazitaxelis a taxane-type antineoplastic agent used for treating prostate cancer. Although typical side effects include neutropenia and fatigue, no studies have investigated eye disorders as a possible side effect, and the details are not clear. Herein, we report our experience of an undeniable case of optic neuropathy caused by cabazitaxel. A 78-year-old man had been diagnosed with prostate cancer (cT3aN1M1b, stage IV) 3 years previously, with a treatment history of bicalutamide, leuprorelin, flutamide, docetaxel, abiraterone, and enzalutamide. Because of a decline in vision during the second and third administration cycles of cabazitaxel, the patient visited an ophthalmologist. He was found to have reduced visual acuity, reduced central critical flicker frequency, narrowed field of vision, and impaired color vision, and was diagnosed with optic neuropathy. Although cabazitaxel administration was continued through 6 cycles, the symptoms were unchanged, and no drastic exacerbation was seen. This patient undeniably developed optic neuropathy due to cabazitaxel. Optic neuropathy due to taxane-type antineoplastic agents has also been reported with paclitaxel or docetaxel, and all precautions should be taken when administering such drugs. Detailed studies that include data from a larger number of facilities should be conducted in the future. PMID:27306820

  10. Exercise as Therapy for Diabetic and Prediabetic Neuropathy.

    PubMed

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

    2015-12-01

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

  11. Diabetic Neuropathy: What is a Total Contact Cast?

    MedlinePlus

    ... Web version Diabetic Neuropathy | What is a Total Contact Cast? What is a total contact cast? A total contact cast is a cast used to treat ulcers ( ... foot--that's why it is called a total contact cast. The cast helps to protect the skin ...

  12. Recent advances in exploring the genetic susceptibility to diabetic neuropathy.

    PubMed

    Politi, Cristina; Ciccacci, Cinzia; D'Amato, Cinzia; Novelli, Giuseppe; Borgiani, Paola; Spallone, Vincenza

    2016-10-01

    Diabetic polyneuropathy and cardiovascular autonomic neuropathy are common and disabling complications of diabetes. Although glycaemic control and cardiovascular risk factors are major contributory elements in its development, diabetic neuropathy recognizes a multifactorial influence and a multiplicity of pathogenetic mechanisms. Thus genetic and environmental factors may contribute to its susceptibility, each with a modest contribution, by targeting various metabolic and microvascular pathways whose alterations intervene in diabetic neuropathy pathogenesis. This review is aimed at describing major data from the available literature regarding genetic susceptibility to diabetic neuropathies. It provides an overview of the genes reported as associated with the development or progression of these complications, i.e. ACE, MTHFR, GST, GLO1, APOE, TCF7L2, VEGF, IL-4, GPX1, eNOS, ADRA2B, GFRA2, MIR146A, MIR128A. The identification of genetic susceptibility can help in both expanding the comprehension of the pathogenetic mechanisms of diabetic nerve damage and identifying biomarkers of risk prediction and response to therapeutic intervention.

  13. Clinicopathological and genetic study of early-onset demyelinating neuropathy.

    PubMed

    Parman, Yesim; Battaloglu, Esra; Baris, Ibrahim; Bilir, Birdal; Poyraz, Mürüvvet; Bissar-Tadmouri, Nisrine; Williams, Anna; Ammar, Nadia; Nelis, Eva; Timmerman, Vincent; De Jonghe, Peter; Najafov, Ayaz; Necefov, Ayaz; Deymeer, Feza; Serdaroglu, Piraye; Brophy, Peter J; Said, G

    2004-11-01

    Autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between the parents or presence of an affected sib suggested autosomal recessive transmission. Screening of various genes known to be involved in CMT4 revealed six mutations of which five are novel. Four of these novel mutations occurred in the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1. All patients tested negative for mutations in EGR2. Histopathological examination of nerve biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion bulb formation, extensive demyelination of isolated fibres and axon loss. We did not discern a specific pattern of histopathology that could be correlated to mutations in a particular gene. PMID:15469949

  14. Periaxin mutations cause a broad spectrum of demyelinating neuropathies.

    PubMed

    Takashima, Hiroshi; Boerkoel, Cornelius F; De Jonghe, Peter; Ceuterick, Chantal; Martin, Jean-Jacques; Voit, Thomas; Schröder, J-Michael; Williams, Anna; Brophy, Peter J; Timmerman, Vincent; Lupski, James R

    2002-06-01

    Previous studies have demonstrated that apparent loss-of-function mutations in the periaxin gene cause autosomal recessive Dejerine-Sottas neuropathy or severe demyelinating Charcot-Marie-Tooth disease. In this report, we extend the associated phenotypes with the identification of two additional families with novel periaxin gene mutations (C715X and R82fsX96) and provide detailed neuropathology. Each patient had marked sensory involvement; two siblings with a homozygous C715X mutation had much worse sensory impairment than motor impairment. Despite early disease onset, these siblings with the C715X mutation had relatively slow disease progression and adult motor impairment typical of classic demyelinating Charcot-Marie-Tooth neuropathy. In contrast, a patient with the homozygous R82fsX96 mutation had a disease course consistent with Dejerine-Sottas neuropathy. The neuropathology of patients in both families was remarkable for demyelination, onion bulb and occasional tomacula formation with focal myelin thickening, abnormalities of the paranodal myelin loops, and focal absence of paranodal septate-like junctions between the terminal loops and axon. Our study indicates a prominent sensory neuropathy resulting from periaxin gene mutations and suggests a role for the carboxyl terminal domain of the periaxin protein. PMID:12112076

  15. SPTLC1 is mutated in hereditary sensory neuropathy, type 1.

    PubMed

    Bejaoui, K; Wu, C; Scheffler, M D; Haan, G; Ashby, P; Wu, L; de Jong, P; Brown, R H

    2001-03-01

    Hereditary sensory neuropathy type 1 (HSN1, MIM 162400; ref. 1) genetically maps to human chromosome 9q22 (refs. 2-4). We report here that the gene encoding a subunit of serine palmitoyltransferase is located within the HSN1 locus, expressed in dorsal root ganglia (DRG) and mutated in HSN1. PMID:11242106

  16. Neuropathological alterations in diabetic truncal neuropathy: evaluation by skin biopsy

    PubMed Central

    Lauria, G.; McArthur, J.; Hauer, P.; Griffin, J.; Cornblath, D.

    1998-01-01

    OBJECTIVES—To describe the neuropathological features in skin biopsies from patients with diabetic truncal neuropathy.
METHODS—Three patients with diabetic truncal neuropathy underwent skin biopsies from both symptomatic and asymptomatic regions of the chest and trunk. After local anaesthesia, biopsies were performed using a 3 mm diameter punch device (Acupunch). Intraepidermal nerve fibres (IENFs), the most distal processes of small myelinated and unmyelinated nerve fibres, were identified after staining with PGP 9.5 as previously described.
RESULTS—Diabetes was diagnosed at the time of the neurological presentation in two, and one was a known diabetic patient. All three had associated sensory-motor polyneuropathy. In all, skin biopsies showed a marked reduction of both epidermal and dermal nerve fibres in the symptomatic dermatomes, compared with skin from asymptomatic truncal areas. In one patient, a follow up skin biopsy when symptoms had improved showed a return of IENFs.
CONCLUSIONS—In diabetic truncal neuropathy, skin biopsies from symptomatic regions show a loss of IENFs. After clinical recovery, there is a return of the IENF population, suggesting that improvement occurs by nerve regeneration. These findings suggest that sensory nerve fibre injury in diabetic truncal neuropathy is distal to or within the sensory ganglia. Skin biopsy provides a possible tool for understanding the pathophysiology of the disease.

 PMID:9810952

  17. Visual Rehabilitation of Persons with Leber's Hereditary Optic Neuropathy.

    ERIC Educational Resources Information Center

    Rudanko, S.-L.

    1995-01-01

    This article presents results of a noncontrolled clinical study of 20 persons with Leber's hereditary optic neuropathy who were treated from 1976 to 1990 at the Low Vision Centre of the Finnish Federation of the Visually Handicapped. The importance of early functional visual rehabilitation is emphasized, as is the use of low vision aids to help…

  18. Testing nerves: an overview of investigations for neuropathy.

    PubMed

    Hiew, Fu Liong; Douis, Hassan; Rajabally, Yusuf A

    2016-09-01

    This article reviews the main investigations available to assess and diagnose patients with neuropathy. It details the most commonly used as well as investigations now becoming routine in neuromuscular centres, and those which are less widely available. Current practice and recent developments are discussed. PMID:27640653

  19. Effects of vibrating insoles on standing balance in diabetic neuropathy.

    PubMed

    Hijmans, Juha M; Geertzen, Jan H B; Zijlstra, Wiebren; Hof, At L; Postema, Klaas

    2008-01-01

    This study investigated the effects on standing balance of random vibrations applied to the plantar side of the feet by vibrating insoles in subjects with neuropathy and nondisabled subjects. In four different conditions (eyes open or closed and with or without an attention-demanding task [ATD]), subjects with neuropathy secondary to diabetes mellitus (n = 17) and nondisabled subjects (n = 15) stood for 60 s on vibrating insoles placed on a force plate. During each condition, the insoles were turned on for 30 s and off for 30 s (random order). The calculated balance measures were mean velocity of the center of pressure displacements and root-mean-square of the velocity of these displacements in the anteroposterior and mediolateral directions. In subjects with neuropathy, an interaction effect between vibration and an ADT was found for balance. No effects of vibration on balance were found in nondisabled subjects. Vibrating insoles improved standing balance in subjects with neuropathy only when attention was distracted. Improvement of the insoles and their activation is needed to make their implementation in daily living possible and effective. PMID:19319766

  20. Cytidine 5′-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats

    PubMed Central

    Emril, Dessy R; Wibowo, Samekto; Meliala, Lucas; Susilowati, Rina

    2016-01-01

    Background Cytidine 5′-diphosphocholine (citicoline) has been shown to have beneficial effects in central nervous system injury as well as in motoric functional recovery after peripheral nerve injury. This study aimed to examine the effect of citicoline on prevention of neuropathic pain in a rat model of sciatic nerve crush injury. Methods Forty experimental rats were divided into four groups. In three groups, the right sciatic nerves were crushed in the mid-thigh region, and a gelatin sponge moistened with 0.4 or 0.8 mL of 100 µmol/L citicoline, or saline 0.4 mL in the control group, was applied. The fourth group of rats was sham-operated, ie the sciatic nerve was exposed with no crush. Functional assessments were performed 4 weeks after crush injury. von Frey filaments (100 g threshold) were used to assess neuropathic pain. In addition, the sciatic functional index and extensor postural thrust (EPT) tests were used to assess motoric function. Results The crush/citicoline 0.4 mL group had a lower percentage of pain (23.53%, n=17) compared with the crush/saline group (53.33%, n=15, P<0.005). The crush/citicoline 0.4 mL group also showed better motoric recovery, as seen in stronger EPT results (P<0.001). However, the sciatic functional index analysis did not show significant differences between groups (P=0.35). The crush/citicoline 0.8 mL group showed a higher percentage of pain (66.67%, n=18) and less EPT recovery. These results may be explained by more severe nerve injury due to compression with a larger administered volume. Conclusion In situ administration of 0.4 mL of 100 µmol/L citicoline prevents the occurrence of neuropathic pain and induces motoric recovery, evaluated by EPT test, 4 weeks after sciatic nerve injury. PMID:27284264

  1. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy.

    PubMed

    Giordano, Carla; Montopoli, Monica; Perli, Elena; Orlandi, Maurizia; Fantin, Marianna; Ross-Cisneros, Fred N; Caparrotta, Laura; Martinuzzi, Andrea; Ragazzi, Eugenio; Ghelli, Anna; Sadun, Alfredo A; d'Amati, Giulia; Carelli, Valerio

    2011-01-01

    Leber's hereditary optic neuropathy, the most frequent mitochondrial disease due to mitochondrial DNA point mutations in complex I, is characterized by the selective degeneration of retinal ganglion cells, leading to optic atrophy and loss of central vision prevalently in young males. The current study investigated the reasons for the higher prevalence of Leber's hereditary optic neuropathy in males, exploring the potential compensatory effects of oestrogens on mutant cell metabolism. Control and Leber's hereditary optic neuropathy osteosarcoma-derived cybrids (11778/ND4, 3460/ND1 and 14484/ND6) were grown in glucose or glucose-free, galactose-supplemented medium. After having shown the nuclear and mitochondrial localization of oestrogen receptors in cybrids, experiments were carried out by adding 100 nM of 17β-oestradiol. In a set of experiments, cells were pre-incubated with the oestrogen receptor antagonist ICI 182780. Leber's hereditary optic neuropathy cybrids in galactose medium presented overproduction of reactive oxygen species, which led to decrease in mitochondrial membrane potential, increased apoptotic rate, loss of cell viability and hyper-fragmented mitochondrial morphology compared with control cybrids. Treatment with 17β-oestradiol significantly rescued these pathological features and led to the activation of the antioxidant enzyme superoxide dismutase 2. In addition, 17β-oestradiol induced a general activation of mitochondrial biogenesis and a small although significant improvement in energetic competence. All these effects were oestrogen receptor mediated. Finally, we showed that the oestrogen receptor β localizes to the mitochondrial network of human retinal ganglion cells. Our results strongly support a metabolic basis for the unexplained male prevalence in Leber's hereditary optic neuropathy and hold promises for a therapeutic use for oestrogen-like molecules.

  2. Stress and strain analysis on the anastomosis site sutured with either epineurial or perineurial sutures after simulation of sciatic nerve injury☆

    PubMed Central

    Liu, Guangyao; Zhang, Qiao; Jin, Yan; Gao, Zhongli

    2012-01-01

    The magnitude of tensile stress and tensile strain at an anastomosis site under physiological stress is an important factor for the success of anastomosis following suturing in peripheral nerve injury treatment. Sciatic nerves from fresh adult cadavers were used to create models of sciatic nerve injury. The denervated specimens underwent epineurial and perineurial suturing. The elastic modulus (40.96 ± 2.59 MPa) and Poisson ratio (0.37 ± 0.02) of the normal sciatic nerve were measured by strain electrical measurement. A resistance strain gauge was pasted on the front, back, left, and right of the edge of the anastomosis site after suturing. Strain electrical measurement results showed that the stress and strain values of the sciatic nerve following perineurial suturing were lower than those following epineurial suturing. Scanning electron microscopy revealed that the sciatic nerve fibers were disordered following epineurial compared with perineurial suturing. These results indicate that the effect of perineurial suturing in sciatic nerve injury repair is better than that of epineurial suturing. PMID:25538753

  3. Multifocal Motor Neuropathy, Multifocal Acquired Demyelinating Sensory and Motor Neuropathy and Other Chronic Acquired Demyelinating Polyneuropathy Variants

    PubMed Central

    Barohn, Richard J.; Katz, Jonathan

    2014-01-01

    Chronic acquired demyelinating neuropathies (CADP) are an important group of immune neuromuscular disorders affecting myelin. These are distinct from chronic inflammatory demyelinating polyneuropathy (CIDP). Classically, CIDP is characterized by proximal and distal weakness, large fiber sensory loss, elevated cerebrospinal fluid (CSF) protein content, demyelinating changes nerve conduction studies or nerve biopsy, and response to immunomodulating treatment. In this chapter we discuss CADP with emphasis on multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), distal acquired demyelinating symmetric (DADS) neuropathy and conclude with less common variants. While each of these entities has distinctive laboratory and electrodiagnostic features that aid in their diagnosis, clinical characteristics are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies. Unlike CIDP, MMN is typically asymmetric and affects only the motor nerve fibers. MMN is a rare disease that presents chronically, over several years of progression affecting the arms are more commonly than the legs. Men are more likely than women to develop MMN. MADSAM should be suspected in patients who have weakness and loss of sensation in primarily one arm or leg which progresses slowly over several months to years. It is important in patient with multifocal demyelinating clinical presentation to distinguish MMN from MADSAM since corticosteroids are not effective in MMN where the mainstay of therapy is intravenous gammaglobulin (IVIg). DADS can be subdivided into DADS-M (associated woth M-protein) and DADS-I which is idioapthic. While DADS-I patients respond somewhat to immunotherapy, DADS-M patients present with distal predominant sensorimotor demyelinating neuropathy phenotype and are notoriously refractory to immunotherapies regardless of antibodies to myelin-associated glycoprotein (MAG). Our knowledge

  4. PKC/MEK inhibitors suppress oxaliplatin-induced neuropathy and potentiate the antitumor effects.

    PubMed

    Tsubaki, Masanobu; Takeda, Tomoya; Tani, Tadahumi; Shimaoka, Hirotaka; Suzuyama, Naohiro; Sakamoto, Kotaro; Fujita, Arisa; Ogawa, Naoki; Itoh, Tatsuki; Imano, Motohiro; Funakami, Yoshinori; Ichida, Seiji; Satou, Takao; Nishida, Shozo

    2015-07-01

    Oxaliplatin is a key drug commonly used in colorectal cancer treatment. Despite high clinical efficacy, its therapeutic application is limited by common, dose-limiting occurrence of neuropathy. As usual symptomatic neuropathy treatments fail to improve the patients' condition, there is an urgent need to advance our understanding of the pathogenesis of neuropathy to propose effective therapy and ensure adequate pain management. Oxaliplatin-induced neuropathy was recently reported to be associated with protein kinase C (PKC) activation. It is unclear, however, whether PKC inhibition can prevent neuropathy. In our current studies, we found that a PKC inhibitor, tamoxifen, inhibited oxaliplatin-induced neuropathy via the PKC/extracellular signal-regulated kinase (ERK)/c-Fos pathway in lumbar spinal cords (lumbar segments 4-6). Additionally, tamoxifen was shown to act in synergy with oxaliplatin to inhibit growth in tumor cells-implanted mice. Moreover, mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, PD0325901, suppressed oxaliplatin-induced neuropathy and enhanced oxaliplatin efficacy. Our results indicate that oxaliplatin-induced neuropathy is associated with PKC/ERK/c-Fos pathway in lumbar spinal cord. Additionally, we demonstrate that disruption of this pathway by PKC and MEK inhibitors suppresses oxaliplatin-induced neuropathy, thereby suggesting that PKC and MEK inhibitors may be therapeutically useful in preventing oxaliplatin-induced neuropathy and could aid in combination antitumor pharmacotherapy.

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

    PubMed Central

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

    2013-01-01

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

  6. Systemic administration of vitamins C and E attenuates nociception induced by chronic constriction injury of the sciatic nerve in rats.

    PubMed

    Riffel, Ana Paula K; de Souza, Jéssica A; Santos, Maria do Carmo Q; Horst, Andréa; Scheid, Taína; Kolberg, Carolina; Belló-Klein, Adriane; Partata, Wania A

    2016-03-01

    Antioxidants have been tested to treat neuropathic pain, and α-Tocopherol (vitamin E--vit. E) and ascorbic acid (vitamin C--vit. C) are potent antioxidants. We assessed the effect of intraperitoneal administration of vit. C (30 mg/kg/day) and vit. E (15 mg/kg/day), given alone or in combination, on the mechanical and thermal thresholds and the sciatic functional index (SFI) in rats with chronic constriction injury (CCI) of the sciatic nerve. We also determined the lipid hydroperoxides and total antioxidant capacity (TAC) in the injured sciatic nerve. Further, we assessed the effects of oral administration of vit. C+vit. E (vit. C+E) and of a combination of vit. C+E and gabapentin (100mg/kg/day, i.p.) on the mechanical and thermal thresholds of CCI rats. The vitamins, whether administered orally or i.p., attenuated the reductions in the mechanical and thermal thresholds induced by CCI. The antinociceptive effect was greater with a combination of vit. C+E than with each vitamin given alone. The SFI was also improved in vitamin-treated CCI rats. Co-administration of vit. C+E and gabapentin induced a greater antinociceptive effect than gabapentin alone. No significant change occurred in TAC and lipid hydroperoxide levels, but TAC increased (45%) while lipid hydroperoxides decreased (38%) in the sciatic nerve from vit. C+E-treated CCI rats. Thus, treatment with a combination of vit. C+E was more effective to treat CCI-induced neuropathic pain than vitamins alone, and the antinociceptive effect was greater with co-administration of vit. C+E and gabapentin than with gabapentin alone. PMID:26855326

  7. Conserved Dopamine Neurotrophic Factor-Transduced Mesenchymal Stem Cells Promote Axon Regeneration and Functional Recovery of Injured Sciatic Nerve

    PubMed Central

    Liu, Yi; Nie, Lin; Zhao, Hua; Zhang, Wen; Zhang, Yuan-Qiang; Wang, Shuai-Shuai; Cheng, Lei

    2014-01-01

    Peripheral nerve injury (PNI) is a common disease that often results in axonal degeneration and the loss of neurons, ultimately leading to limited nerve regeneration and severe functional impairment. Currently, there are no effective treatments for PNI. In the present study, we transduced conserved dopamine neurotrophic factor (CDNF) into mesenchymal stem cells (MSCs) in collagen tubes to investigate their regenerative effects on rat peripheral nerves in an in vivo transection model. Scanning electron microscopy of the collagen tubes demonstrated their ability to be resorbed in vivo. We observed notable overexpression of the CDNF protein in the distal sciatic nerve after application of CDNF-MSCs. Quantitative analysis of neurofilament 200 (NF200) and S100 immunohistochemistry showed significant enhancement of axonal and Schwann cell regeneration in the group receiving CDNF-MSCs (CDNF-MSCs group) compared with the control groups. Myelination thickness, axon diameter and the axon-to fiber diameter ratio (G-ratio) were significantly higher in the CDNF-MSCs group at 8 and 12 weeks after nerve transection surgery. After surgery, the sciatic functional index, target muscle weight, wet weight ratio of gastrocnemius muscle and horseradish peroxidase (HRP) tracing demonstrated functional recovery. Light and electron microscopy confirmed successful regeneration of the sciatic nerve. The greater numbers of HRP-labeled neuron cell bodies and increased sciatic nerve index values (SFI) in the CDNF-MSCs group suggest that CDNF exerts neuroprotective effects in vivo. We also observed higher target muscle weights and a significant improvement in muscle atrophism in the CDNF-MSCs group. Collectively, these findings indicate that CDNF gene therapy delivered by MSCs is capable of promoting nerve regeneration and functional recovery, likely because of the significant neuroprotective and neurotrophic effects of CDNF and the superior environment offered by MSCs and collagen tubes. PMID

  8. F-actin distribution at nodes of Ranvier and Schmidt-Lanterman incisures in mammalian sciatic nerves.

    PubMed

    Kun, Alejandra; Canclini, Lucía; Rosso, Gonzalo; Bresque, Mariana; Romeo, Carlos; Hanusz, Alicia; Cal, Karina; Calliari, Aldo; Sotelo Silveira, José; Sotelo, José R

    2012-07-01

    Very little is known about the function of the F-actin cytoskeleton in the regeneration and pathology of peripheral nerve fibers. The actin cytoskeleton has been associated with maintenance of tissue structure, transmission of traction and contraction forces, and an involvement in cell motility. Therefore, the state of the actin cytoskeleton strongly influences the mechanical properties of cells and intracellular transport therein. In this work, we analyze the distribution of F-actin at Schmidt-Lanterman Incisures (SLI) and nodes of Ranvier (NR) domains in normal, regenerating and pathologic Trembler J (TrJ/+) sciatic nerve fibers, of rats and mice. F-actin was quantified and it was found increased in TrJ/+, both in SLI and NR. However, SLI and NR of regenerating rat sciatic nerve did not show significant differences in F-actin, as compared with normal nerves. Cytochalasin-D and Latrunculin-A were used to disrupt the F-actin network in normal and regenerating rat sciatic nerve fibers. Both drugs disrupt F-actin, but in different ways. Cytochalasin-D did not disrupt Schwann cell (SC) F-actin at the NR. Latrunculin-A did not disrupt F-actin at the boundary region between SC and axon at the NR domain. We surmise that the rearrangement of F-actin in neurological disorders, as presented here, is an important feature of TrJ/+ pathology as a Charcot-Marie-Tooth (CMT) model.

  9. Repeatability of measuring sciatic nerve excursion during a modified passive straight leg raise test with ultrasound imaging.

    PubMed

    Ridehalgh, Colette; Moore, Ann; Hough, Alan

    2012-12-01

    The purpose of this study was to establish the reliability of a frame-by-frame cross correlation method of assessing longitudinal sciatic nerve excursion motion using real time ultrasound imaging during a modified passive straight leg raise (SLR) test. Eighteen asymptomatic participants (age range 19-68 years) lay on their sides on a purpose made jig and the sciatic nerve in the posterior thigh was imaged during knee extension at 30° and then 60° of hip flexion (HF). Participants were re-tested ≥48 h later. The ultrasound images were analysed off-line using cross correlation software. Results demonstrated excellent repeatability of in vivo sciatic nerve excursion during a modified SLR (HF30° ICC 0.92, CI 0.79-0.97, SEM 0.69; HF60° ICC 0.96, CI 0.89-0.99, SEM 0.87). The authors also identify points of good practise to ensure an accurate as possible measurement of nerve excursion using this method. These include breaking down larger movements into sub-components, visually tracking the moving nerve during the tracking procedure, and ensuring the optimal image is captured prior to analysis. The use of ultrasound imaging in lower limb nerve dysfunction will enhance the understanding of how nerves move in vivo during neurodynamic testing, as well as being able to identify possible alteration to nerve movements in patients with neuropathic pain states.

  10. Three-dimensional conformal intensity-modulated radiation therapy of left femur foci does not damage the sciatic nerve

    PubMed Central

    Xu, Wanlong; Zhao, Xibin; Wang, Qing; Sun, Jungang; Xu, Jiangbo; Zhou, Wenzheng; Wang, Hao; Yan, Shigui; Yuan, Hong

    2014-01-01

    During radiotherapy to kill femoral hydatid tapeworms, the sciatic nerve surrounding the focus can be easily damaged by the treatment. Thus, it is very important to evaluate the effects of radiotherapy on the surrounding nervous tissue. In the present study, we used three-dimensional, conformal, intensity-modulated radiation therapy to treat bilateral femoral hydatid disease in Meriones meridiani. The focus of the hydatid disease on the left femur was subjected to radiotherapy (40 Gy) for 14 days, and the right femur received sham irradiation. Hematoxylin-eosin staining, electron microscopy, and terminal deoxynucleotidyl transferase-dUTP nick end labeling assays on the left femurs showed that the left sciatic nerve cell structure was normal, with no obvious apoptosis after radiation. Trypan blue staining demonstrated that the overall protoscolex structure in bone parasitized with Echinococcus granulosus disappeared in the left femur of the animals after treatment. The mortality of the protoscolex was higher in the left side than in the right side. The succinate dehydrogenase activity in the protoscolex in bone parasitized with Echinococcus granulosus was lower in the left femur than in the right femur. These results suggest that three-dimensional conformal intensity-modulated radiation therapy achieves good therapeutic effects on the secondary bone in hydatid disease in Meriones meridiani without damaging the morphology or function of the sciatic nerve. PMID:25422645

  11. Goji fruit (Lycium barbarum) protects sciatic nerve function against crush injury in a model of diabetic stress.

    PubMed

    Simonyan, K V; Avetisyan, L G; Chavushyan, V A

    2016-09-01

    Excess fructose consumption causes changes in functioning of the central and peripheral nervous systems, which increase the vulnerability of peripheral nerves to traumatic injury. The aim of this study was to evaluate the electrophysiological parameters of responses of motoneurons of the spinal cord at high-frequency stimulation of the distal part of the injured sciatic nerve in a model of diabetic stress under action of Lycium barbarum (LB). Male albino rats were given with drinking water with 50% concentration of dietary fructose for 6 weeks. Starting on the 7th week a crush injury of the left sciatic nerve was carried out. Some of the animals received fructose post-injury for 3 weeks and some of the animals received fructose+dry LB fruits for 3 weeks. In the fructose+crush+LВ group a relatively proportional division of tetanic and posttetanic potentiation and depression in responses of ipsilateral and contralateral motoneurons was observed, which would suggest the modulatory role of LB in short-term synaptic plasticity formation. Generally, LB fruit is able to modulate central nervous system reorganization, amplifying positive adaptive changes that improve functional recovery and promote selective target reinnervation in high fructose-diet rats with sciatic nerve crush-injury. PMID:27424529

  12. Long-term effect of ropivacaine nanoparticles for sciatic nerve block on postoperative pain in rats

    PubMed Central

    Wang, Zi; Huang, Haizhen; Yang, Shaozhong; Huang, Shanshan; Guo, Jingxuan; Tang, Qi; Qi, Feng

    2016-01-01

    Purpose The analgesic effect of ropivacaine (Rop) for nerve block lasts only ~3–6 hours for single use. The aim of this study was to develop long-acting regional anesthetic Rop nanoparticles and investigate the effects of sciatic nerve block on postoperative pain in rats. Materials and methods Rop nanoparticles were developed using polyethylene glycol-co-polylactic acid (PELA). One hundred and twenty adult male Wistar rats were randomly divided into four groups (n=30, each): Con (control group; 0.9% saline, 200 µL), PELA (PELA group; 10 mg), Rop (Rop group; 0.5%, 200 µL), and Rop-PELA (Rop-PELA group; 10%, 10 mg). Another 12 rats were used for the detection of Rop concentration in plasma. The mechanical withdrawal threshold and thermal withdrawal latency were measured at 2 hours, 4 hours, 8 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after incision. The expression of c-FOS was determined by immunohistochemistry at 2 hours, 8 hours, 48 hours, and 7 days. Nerve and organ toxicities were also evaluated at 7 days. Results The duration of Rop absorption in the plasma of the Rop-PELA group was longer (>8 hours) than that of the Rop group (4 hours). Mechanical withdrawal threshold and thermal withdrawal latency in the Rop-PELA group were higher than that in other groups (4 hours–3 days). c-FOS expression in the Rop-PELA group was lower than that in the control group at 2 hours, 8 hours, and 48 hours and lower than that in the Rop group at 8 hours and 48 hours after paw incision. Slight foreign body reactions were observed surrounding the sciatic nerve at 7 days. No obvious pathophysiological change was found in the major organs after Rop-PELA administration at 7 days. Conclusion Rop-PELA provides an effective analgesia for nerve block over 3 days after single administration, and the analgesic mechanism might be mediated by the regulation of spinal c-FOS expression. However, its potential long-term tissue toxicity needs to be further investigated. PMID:27274236

  13. A new analgesic method, two-minute sciatic nerve press, for immediate pain relief: a randomized trial

    PubMed Central

    He, Jiman; Wu, Bin; Jiang, Xianrong; Zhang, Fenglin; Zhao, Tao; Zhang, Wenlon

    2008-01-01

    Background Current analgesics have drawbacks such as delays in acquisition, lag-times for effect, and side effects. We recently presented a preliminary report of a new analgesic method involving a two-minute sciatic nerve press, which resulted in immediate short-term relief of pain associated with dental and renal diseases. The present study investigated whether this technique was effective for pain associated with other disease types, and whether the relief was effective for up to one hour. Methods This randomized, placebo-controlled, parallel-group trial was conducted in four hospitals in Anhui Province, China. Patients with pain were sequentially recruited by participating physicians during clinic visits, and 135 patients aged 15 – 80 years were enrolled. Dental disease patients included those with acute pulpitis and periapical abscesses. Renal disease patients included those with kidney infections and/or stones. Tumor patients included those with nose, breast, stomach and liver cancers, while Emergency Room patients had various pathologies. Patients were randomly assigned to receive a "sciatic nerve press" in which pressure was applied simultaneously to the sciatic nerves at the back of both thighs, or a "placebo press" in which pressure was applied to a parallel region on the front of the thighs. Each fist applied a pressure of 11 – 20 kg for 2 minutes. Patients rated their level of pain before and after the procedure. Results The "sciatic nerve press" produced immediate relief of pain in all patient groups. Emergency patients reported a 43.5% reduction in pain (p < 0.001). Significant pain relief for dental, renal and tumor patients lasted for 60 minutes (p < 0.001). The peak pain relief occurred at the 10 – 20th minutes, and the relief decreased 47% by the 60th minutes. Conclusion Two minutes of pressure on both sciatic nerves produced immediate significant short-term conduction analgesia. This technique is a convenient, safe and powerful method for

  14. Retrobulbar optic neuropathy secondary to isolated sphenoid sinus disease

    PubMed Central

    Chafale, Vishal Annaji; Lahoti, Satish Arunkumar; Pandit, Alak; Gangopadhyay, Goutam; Biswas, Atanu

    2015-01-01

    Paranasal sinus disease can cause a condition that mimics optic neuritis. Simultaneous appearance of both diseases would create etiological dilemma. We report two cases of retrobulbar optic neuropathy secondary to isolated sphenoid sinus disease. In the case of a 65-year-old female who had presented with acute loss of vision in the left eye associated with left-sided frontal headache which subsequently turned out to be caused by optic nerve compression at the orbital apex due to collection in abnormally pneumatized left lesser wing of the sphenoid. In another case, a 65-year-old lady had presented with symptoms of bilateral retrobulbar optic neuropathy which was found to be due to direct compression of optic nerves at the orbital apex secondary to metastases from breast carcinoma. PMID:25883489

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

    PubMed

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

    2014-06-01

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

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

    PubMed

    Kelly, John J

    2008-01-01

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

  17. [Acquired inflammatory neuropathies in children and their therapy].

    PubMed

    Kaciński, M

    2001-01-01

    Neuropathies where there is an association with acquired peripheral nerves dysfunction and inflammation include inflammatory neuropathies (IN), as well as sequelae of vaccinations involving peripheral nerves. In a small portion of these diseases central nervous system is involved. In the years 1996-2000, among 22 children with acute flaccid paresis who were hospitalized in the Kraków Department of Paediatric Neurology, there were 16 patients with IN, including 13 with Guillain-Barré syndrome, single cases of Miller-Fisher syndrome, chronic inflammatory demyelinating polyneuropathy involving central nervous system and neuroborreliosis. Additionally, four children were hospitalized for optic neuritis. The author presents data on aetiology, electrophysiology and follow-up of these patients, as well as describes the management and outcome. Apart from their cognitive and practical value, these data significantly correspond with the currently implemented program of poliomyelitis eradication.

  18. Rare cause of paraparesis: bilateral obturator neuropathy after hysterosalpingectomy.

    PubMed

    López-Blanco, Roberto; Mejía-Jiménez, Inmaculada; de Fuenmayor-Fernández de la Hoz, Carlos Pablo; Ruiz-Morales, Juan

    2015-01-01

    Bilateral obturator nerve injury during pelvic surgery is an infrequent cause of lower limb paraparesis. We report the case of a 45-year-old woman with a large uterine leiomyoma who underwent simple total hysterectomy and bilateral salpingectomy. At 24 h after the surgery, the patient noticed loss of muscle strength when adducting both legs. She had no problem with other movements and no sensory or sphincter abnormalities. Neurological examination confirmed that there was loss of strength only in the adductor muscles, with preserved sensory function and reflexes, suggesting bilateral obturator nerve involvement. Pelvic MRI showed a small postsurgical haematoma in the Douglas recess, but far from the obturator nerves. 2 weeks later, electromyography showed positive sharp waves and low motor unit recruitment in the adductor magnus muscles, confirming acute, bilateral obturator nerve neuropathy. The few cases of bilateral obturator neuropathy that have been reported were mostly related to abdominopelvic interventions. PMID:26689250

  19. Practical rules for electrodiagnosis in suspected multifocal motor neuropathy.

    PubMed

    Bromberg, Mark B; Franssen, Hessel

    2015-03-01

    Multifocal motor neuropathy (MMN) with conduction block (CB) is a rare chronic immune-mediated neuropathy, but important to diagnose as it is treatable. The key features in prototypic MMN are electrodiagnostic demonstration of focal CB away from common sites of entrapment and normal sensory conduction across these sites. However, there are challenges in distinguishing CB from the effects of abnormal temporal dispersion. Consensus electrodiagnostic criteria, reinforced by modeling studies, are available to support definite or probable CB. In addition, consideration of technical issues can guard against false-positive and false-negative conclusions. These include limb temperature, stimulus site, inadvertent stimulating electrode movement, and supramaximal and submaximal responses, as well as the possibility of Martin-Gruber anastamosis. Robust evidence supports the treatment of MMN with intravenous immunoglobulin, and guidelines have been developed. Application of practical and simple rules including a 4-step diagnostic algorithm can help practitioners correctly diagnose this treatable condition and improve patient outcomes.

  20. Peroneal neuropathy misdiagnosed as L5 radiculopathy: a case report

    PubMed Central

    2013-01-01

    Objective The purpose of this case report is to describe a patient who presented with a case of peroneal neuropathy that was originally diagnosed and treated as a L5 radiculopathy. Clinical features A 53-year old female registered nurse presented to a private chiropractic practice with complaints of left lateral leg pain. Three months earlier she underwent elective left L5 decompression surgery without relief of symptoms. Intervention and outcome Lumbar spine MRI seven months prior to lumbar decompression surgery revealed left neural foraminal stenosis at L5-S1. The patient symptoms resolved after she stopped crossing her legs. Conclusion This report discusses a case of undiagnosed peroneal neuropathy that underwent lumbar decompression surgery for a L5 radiculopathy. This case study demonstrates the importance of a thorough clinical examination and decision making that ensures proper patient diagnosis and management. PMID:23618508

  1. Sympathetic skin response in acute sensory ataxic neuropathy.

    PubMed

    Arunodaya, G R; Taly, A B; Swamy, H S

    1995-05-01

    Sympathetic skin response (SSR) is a recently described objective method of studying sudomotor sympathetic nerve function and has been studied in a variety of peripheral neuropathies. We report SSR changes in nine patients with acute sensory ataxic neuropathy (ASAN). All had severe sensory and mild motor nerve conduction abnormalities; five had dysautonomia. SSR, elicited by electric shock and cough stimuli, was absent in three patients. Latency was normal in all when SSR was present. Two patients had SSR amplitude of 0.2 mV or less. Absence of SSR did not correlate with dysautonomia, absence of sensory nerve action potential or motor nerve conduction abnormalities. Follow up SSR studies revealed return of absent SSR in one patient over a period of 3 months, despite persistence of ataxia. To our knowledge, this is the first report of SSR changes in ASAN.

  2. Suspected hypothyroid-associated neuropathy in a female rottweiler dog

    PubMed Central

    Rushton, James Oliver; Leschnik, Michael; Nell, Barbara

    2013-01-01

    A 7-year-old, 46-kg spayed female rottweiler dog was presented with sudden onset of disorientation, bilateral convergent strabismus, and enophthalmos. Diagnostic workup revealed hypothyroid-associated cranial neuropathy. Symptoms abated considerably upon treatment with levothyroxine-sodium (T4) at an initial dose of 800 μg/kg body weight (BW), PO, q12h, which was reduced 3 days later to 600 μg/kg BW, q12h due to severe agitation and panting. Two weeks later the dosage of the levothyroxine-sodium (T4) was reduced to 400 μg/kg BW in the morning and 600 μg/kg BW in the evening. Eight weeks after the initial presentation, the dog had recovered with only mild convergent strabismus in the right eye. This is the first case report of suspected hypothyroid-associated neuropathy resulting in these symptoms. PMID:24082164

  3. Leber's hereditary optic neuropathy associated with multiple sclerosis: Harding's syndrome.

    PubMed

    Parry-Jones, A R; Mitchell, J D; Gunarwardena, W J; Shaunak, S

    2008-04-01

    We describe a 32-year-old woman with sequential, severe, painless visual loss in one eye and then the other, and three temporally distinct episodes of neurological disturbance suggestive of demyelination in the spinal cord. She was positive for the T14484C mutation in the mitochondrial genome, one of three common mutations causing Leber's hereditary optic neuropathy. In addition, MRI identified areas of demyelination within the periventricular white matter of the brain and within the spinal cord. The coexistence of multiple sclerosis and Leber's hereditary optic neuropathy (Harding's syndrome) is known to occur more often than would be expected by chance; therefore, screening for the Leber's mutations in multiple sclerosis patients with severe visual loss should be considered because this has important prognostic and genetic implications.

  4. New perspectives in the diagnosis and management of enteric neuropathies.

    PubMed

    Knowles, Charles H; Lindberg, Greger; Panza, Emanuele; De Giorgio, Roberto

    2013-04-01

    Chronic disturbances of gastrointestinal function encompass a wide spectrum of clinical disorders that range from common conditions with mild-to-moderate symptoms to rare diseases characterized by a severe impairment of digestive function, including chronic pain, vomiting, bloating and severe constipation. Patients at the clinically severe end of the spectrum can have profound changes in gut transit and motility. In a subset of these patients, histopathological analyses have revealed abnormalities of the gut innervation, including the enteric nervous system, termed enteric neuropathies. This Review discusses advances in the diagnosis and management of the main clinical entities--achalasia, gastroparesis, intestinal pseudo-obstruction and chronic constipation--that result from enteric neuropathies, including both primary and secondary forms. We focus on the various evident neuropathologies (degenerative and inflammatory) of these disorders and, where possible, present the specific implications of histological diagnosis to contemporary treatment. This knowledge could enable the future development of novel targeted therapeutic approaches. PMID:23399525

  5. [Differential radiodiagnosis of odontogenic mandibular osteomyelitis accompanied by trigeminal neuropathy].

    PubMed

    Solonskaia, N S; Zorina, I S

    2011-01-01

    This paper deals with the results of radiation examination in 43 patients with clinical manifestations of mandibular osteomyelitis. In 13 of them, the disease was accompanied by trigeminal neuropathy. The radiation semiotics of the changes occurring in the mandibular bone and its adjacent soft tissues in different phases of osteomyelitis is described. Comparative analysis of orthopantomograms and the images obtained by multislice spiral computed tomography has revealed the advantage of the latter in identifying insignificant changes in bone tissue and damages to the mandibular canal. Ultrasound study is of more informative value in detecting soft tissue changes in this area. High-technology radiodiagnostic techniques play a leading role in the differentiation of odontogenic and non-odontogenic trigeminal neuropathies.

  6. Inactivation of TNF-α ameliorates diabetic neuropathy in mice

    PubMed Central

    Yamakawa, Isamu; Terashima, Tomoya; Katagi, Miwako; Oi, Jiro; Urabe, Hiroshi; Sanada, Mitsuru; Kawai, Hiromichi; Chan, Lawrence; Yasuda, Hitoshi; Maegawa, Hiroshi; Kimura, Hiroshi

    2011-01-01

    Tumor necrosis factor (TNF)-α is a potent proinflammatory cytokine involved in the pathogenesis of diabetic neuropathy. We inactivated TNF-α to determine if it is a valid therapeutic target for the treatment of diabetic neuropathy. We effected the inactivation in diabetic neuropathy using two approaches: by genetic inactivation of TNF-α (TNF-α−/− mice) or by neutralization of TNF-α protein using the monoclonal antibody infliximab. We induced diabetes using streptozotocin in wild-type and TNF-α−/− mice. We measured serum TNF-α concentration and the level of TNF-α mRNA in the dorsal root ganglion (DRG) and evaluated nerve function by a combination of motor (MNCV) and sensory (SNCV) nerve conduction velocities and tail flick test, as well as cytological analysis of intraepidermal nerve fiber density (IENFD) and immunostaining of DRG for NF-κB p65 serine-276 phosphorylated and cleaved caspase-3. Compared with nondiabetic mice, TNF-α+/+ diabetic mice displayed significant impairments of MNCV, SNCV, tail flick test, and IENFD as well as increased expression of NF-κB p65 and cleaved caspase-3 in their DRG. In contrast, although nondiabetic TNF-α−/− mice showed mild abnormalities of IENFD under basal conditions, diabetic TNF-α−/− mice showed no evidence of abnormal nerve function tests compared with nondiabetic mice. A single injection of infliximab in diabetic TNF-α+/+ mice led to suppression of the increased serum TNF-α and amelioration of the electrophysiological and biochemical deficits for at least 4 wk. Moreover, the increased TNF-α mRNA expression in diabetic DRG was also attenuated by infliximab, suggesting infliximab's effects may involve the local suppression of TNF-α. Infliximab, an agent currently in clinical use, is effective in targeting TNF-α action and expression and amelioration of diabetic neuropathy in mice. PMID:21810933

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

    PubMed Central

    Gibbons, Christopher H; Freeman, Roy

    2011-01-01

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

  8. A new device to quantify tactile sensation in neuropathy

    PubMed Central

    Selim, M.M.; Brink, T.S.; Hodges, J.S.; Wendelschafer-Crabb, G.; Foster, S.X.Y.-L.; Nolano, M.; Provitera, V.; Simone, D.A.

    2011-01-01

    Objective: To devise a rapid, sensitive method to quantify tactile threshold of finger pads for early detection and staging of peripheral neuropathy and for use in clinical trials. Methods: Subjects were 166 healthy controls and 103 patients with, or at risk for, peripheral neuropathy. Subjects were screened by questionnaire. The test device, the Bumps, is a checkerboard-like smooth surface with 12 squares; each square encloses 5 colored circles. The subject explores the circles of each square with the index finger pad to locate the one circle containing a small bump. Bumps in different squares have different heights. Detection threshold is defined as the smallest bump height detected. In some subjects, a 3-mm skin biopsy from the tested finger pad was taken to compare density of Meissner corpuscles (MCs) to bump detection thresholds. Results: The mean (±SEM) bump detection threshold for control subjects was 3.3 ± 0.10 μm. Threshold and test time were age related, older subjects having slightly higher thresholds and using more time. Mean detection threshold of patients with neuropathy (6.2 ± 0.35 μm) differed from controls (p < 0.001). A proposed threshold for identifying impaired sensation had a sensitivity of 71% and specificity of 74%. Detection threshold was higher when MC density was decreased. Conclusions: These preliminary studies suggest that the Bumps test is a rapid, sensitive, inexpensive method to quantify tactile sensation of finger pads. It has potential for early diagnosis of tactile deficiency in subjects suspected of having neuropathy, for staging degree of tactile deficit, and for monitoring change over time. PMID:21555731

  9. Obturator neuropathy: a cause of exercise-related groin pain.

    PubMed

    Brukner, P; Bradshaw, C; McCrory, P

    1999-05-01

    Obturator neuropathy is a cause of exercise-related groin pain, particularly in those who play sports that involve much running, twisting and turning, and kicking. Symptoms include pain that begins insidiously at the adductor origin on the pubic bone and worsens with exercise. Diagnostic measures include reproduction of pain by stretching the pectineus muscle after exercise, electromyography, and a local anesthetic block of the obturator nerve. Surgery allows most patients to resume previous levels of activity.

  10. Postural sway in diabetic peripheral neuropathy among Indian elderly

    PubMed Central

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

    2015-01-01

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

  11. Isolated musculocutaneous neuropathy in an adolescent baseball pitcher.

    PubMed

    Henry, Dorlyne; Bonthius, Daniel J

    2011-12-01

    Injury of the musculocutaneous nerve very rarely occurs in the absence of concomitant injury to other components of the brachial plexus. Until now, the few cases of isolated musculocutaneous nerve palsies have been reported only in adults. We report a case of isolated musculocutaneous neuropathy in a uniquely talented adolescent baseball pitcher. The biomechanics underlying this adolescent's ability to throw with high velocity likely contributed to the musculocutaneous nerve injury in this case.

  12. Mitochondrial dysfunction in distal axons contribute to HIV sensory neuropathy

    PubMed Central

    Lehmann, Helmar C.; Chen, Weiran; Borzan, Jasenka; Mankowski, Joseph; Höke, Ahmet

    2010-01-01

    Objective Accumulation of mitochondrial DNA (mtDNA) damage has been associated with aging and abnormal oxidative metabolism. We hypothesized that in human immunodeficiency virus associated sensory neuropathy (HIV-SN), damaged mtDNA accumulates in distal nerve segments and that a spatial pattern of mitochondrial dysfunction contribute to the distal degeneration of sensory nerve fibers. Methods We measured levels of common deletion mutations in mtDNA and expression levels of mitochondrial respiratory chain complexes of matched proximal and distal nerve specimens from patients with and without HIV-SN. In mitochondria isolated from peripheral nerves of simian immunodeficiency virus (SIV) infected macaques, a model of HIV-SN, we measured mitochondrial function and generation of reactive oxygen species. Results We identified increased levels of mtDNA common deletion mutation in post-mortem sural nerves of patients with HIV-SN as compared to uninfected patients or HIV patients without sensory neuropathy. Furthermore, we found that common deletion mutation in mtDNA was more prevalent in distal sural nerves compared to dorsal root ganglia. In a primate model of HIV-SN, freshly isolated mitochondria from sural nerves of macaques infected with a neurovirulent strain of SIV showed impaired mitochondrial function compared to mitochondria from proximal nerve segments. Interpretation Our findings suggest that mtDNA damage accumulates in distal mitochondria of long axons, especially in patients with HIV-SN, and that this may lead to reduced mitochondrial function in distal nerves relative to proximal segments. Although our findings are based on HIV-SN, if confirmed in other neuropathies, these observations could explain the length-dependent nature of most axonal peripheral neuropathies. PMID:21280080

  13. Sciatic nerve regeneration through alginate with tubulation or nontubulation repair in cat.

    PubMed

    Sufan, W; Suzuki, Y; Tanihara, M; Ohnishi, K; Suzuki, K; Endo, K; Nishimura, Y

    2001-03-01

    A novel material for nerve regeneration, alginate, was employed in both tubulation and nontubulation repair of a long peripheral nerve defect injury. Twelve cats underwent severing of the right sciatic nerve to generate a 50-mm gap, which was treated by tubulation repair (n = 6) or nontubulation repair (n = 6). In the tubulation group, a nerve conduit consisting of polyglycolic acid mesh tube filled with alginate sponge was implanted into the gap and the tube was sutured to both nerve stumps. In the nontubulation group, the nerve defect was repaired by a simple interpolation of two pieces of alginate sponge without any suture. The animals in both groups exhibited similar recovery of locomotor function. Three months postoperatively, successful axonal elongation and reinnervation in both the afferent and efferent systems were detected by electrophysiological examinations. Intracellular electrical activity was also recorded, which is directly indicative of continuity of the regenerated nerve and restoration of the spinal reflex circuit. Eight months after operation, many regenerated myelinated axons with fascicular organization by perineurial cells were observed within the gap, peroneal and tibial branches were found in both groups, while no alginate residue was found within the regenerated nerves. In morphometric analysis of the axon density and diameter, there were no significant differences between the two groups. These results suggest that alginate is a potent material for promoting peripheral nerve regeneration. It can also be concluded that the nontubulation method is a possible repair approach for peripheral nerve defect injury.

  14. Curcumin promotes nerve regeneration and functional recovery after sciatic nerve crush injury in diabetic rats.

    PubMed

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

    2016-01-01

    Curcumin is capable of promoting peripheral nerve regeneration in normal condition. However, it is unclear whether its beneficial effect on nerve regeneration still exists under diabetic mellitus. The present study was designed to investigate such a possibility. Diabetes in rats was developed by a single dose of streptozotocin at 50 mg/kg. Immediately after nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with curcumin (50 mg/kg, 100 mg/kg and 300 mg/kg), or normal saline, respectively. The axonal regeneration was investigated by morphometric analysis and retrograde labeling. The functional recovery was evaluated by electrophysiological studies and behavioral analysis. Axonal regeneration and functional recovery was significantly enhanced by curcumin, which were significantly better than those in vehicle saline group. In addition, high doses of curcumin (100 mg/kg and 300 mg/kg) achieved better axonal regeneration and functional recovery than low dose (50 mg/kg). In conclusion, curcumin is capable of promoting nerve regeneration after sciatic nerve crush injury in diabetes mellitus, highlighting its therapeutic values as a neuroprotective agent for peripheral nerve injury repair in diabetes mellitus.

  15. Swimming exercise in the acute or late phase after sciatic nerve crush accelerates nerve regeneration.

    PubMed

    Teodori, Rosana Macher; Betini, Joice; de Oliveira, Larissa Salgado; Sobral, Luciane Lobato; Takeda, Sibele Yoko Mattozo; de Lima Montebelo, Maria Imaculada

    2011-01-01

    There is no consensus about the best time to start exercise after peripheral nerve injury. We evaluated the morphological and functional characteristics of the sciatic nerves of rats that began to swim immediately after crush nerve injury (CS1), those that began to swim 14 days after injury (CS14), injured rats not submitted to swimming (C), and uninjured rats submitted to swimming (S). After 30 days the number of axons in CS1 and CS14 was lower than in C (P < 0.01). The diameter of axons and nerve fibers was larger in CS1 (P < 0.01) and CS14 (P < 0.05) than in C, and myelin sheath thickness was lower in all crushed groups (P < 0.05). There was no functional difference between CS1 and CS14 (P > 0.05). Swimming exercise applied during the acute or late phase of nerve injury accelerated nerve regeneration and synaptic elimination after axonotmesis, suggesting that exercise may be initiated immediately after injury.

  16. High-frequency stimulation selectively blocks different types of fibers in frog sciatic nerve.

    PubMed

    Joseph, Laveeta; Butera, Robert J

    2011-10-01

    Conduction block using high-frequency alternating current (HFAC) stimulation has been shown to reversibly block conduction through various nerves. However, unlike simulations and experiments on myelinated fibers, prior experimental work in our lab on the sea-slug, Aplysia, found a nonmonotonic relationship between frequency and blocking thresholds in the unmyelinated fibers. To resolve this discrepancy, we investigated the effect of HFAC waveforms on the compound action potential of the sciatic nerve of frogs. Maximal stimulation of the nerve produces a compound action potential consisting of the A-fiber and C-fiber components corresponding to the myelinated and unmyelinated fibers' response. In our study, HFAC waveforms were found to induce reversible block in the A-fibers and C-fibers for frequencies in the range of 5-50 kHz and for amplitudes from 0.1-1 mA. Although the A-fibers demonstrated the monotonically increasing threshold behavior observed in published literature, the C-fibers displayed a nonmonotonic relationship, analogous to that observed in the unmyelinated fibers of Aplysia. This differential blocking behavior observed in myelinated and unmyelinated fibers during application of HFAC waveforms has diverse implications for the fields of selective stimulation and pain management.

  17. Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair.

    PubMed

    Perussi Biscola, Natalia; Politti Cartarozzi, Luciana; Ferreira Junior, Rui Seabra; Barraviera, Benedito; Leite Rodrigues de Oliveira, Alexandre

    2016-01-01

    Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA) without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS) at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons. PMID:27446617

  18. Essential Oil of Ocimum basilicum L. and (-)-Linalool Blocks the Excitability of Rat Sciatic Nerve.

    PubMed

    Medeiros Venancio, Antonio; Ferreira-da-Silva, Francisco Walber; da Silva-Alves, Kerly Shamyra; de Carvalho Pimentel, Hugo; Macêdo Lima, Matheus; Fraga de Santana, Michele; Barreto Alves, Péricles; Batista da Silva, Givanildo; Leal-Cardoso, José Henrique; Marchioro, Murilo

    2016-01-01

    The racemate linalool and its levogyrus enantiomer [(-)-LIN] are present in many essential oils and possess several pharmacological activities, such as antinociceptive and anti-inflammatory. In this work, the effects of essential oil obtained from the cultivation of the Ocimum basilicum L. (EOOb) derived from Germplasm Bank rich in (-)-LIN content in the excitability of peripheral nervous system were studied. We used rat sciatic nerve to investigate the EOOb and (-)-LIN effects on neuron excitability and the extracellular recording technique was used to register the compound action potential (CAP). EOOb and (-)-LIN blocked the CAP in a concentration-dependent way and these effects were reversible after washout. EOOb blocked positive amplitude of 1st and 2nd CAP components with IC50 of 0.38 ± 0.2 and 0.17 ± 0.0 mg/mL, respectively. For (-)-LIN, these values were 0.23 ± 0.0 and 0.13 ± 0.0 mg/mL. Both components reduced the conduction velocity of CAP and the 2nd component seems to be more affected than the 1st component. In conclusion EOOb and (-)-LIN inhibited the excitability of peripheral nervous system in a similar way and potency, revealing that the effects of EOOb on excitability are due to the presence of (-)-LIN in the essential oil.

  19. The influence of bacterial collagenase on regeneration of severed rat sciatic nerves.

    PubMed

    Wehling, P; Pak, M; Cleveland, S; Nieper, R

    1992-01-01

    Regeneration of peripheral nerve fibers is impeded by the formation of scar tissue at the site of injury. The possible beneficial effect of collagenase on nerve regeneration was studied using clinical, neurophysiological (evoked potentials) and histological (nerve fiber counts) methods. The sciatic nerves of rats were transected and the severed ends abutted and sewn together. In one series, the area about the lesion was covered with fibrin adhesive and infused with either isotonic saline (controls) or collagenase (treatment group). In the other series, the severed ends of the nerve were inserted into a silicone tube and separated by a collagen plug, which was infused with either saline or collagenase. Compared to the controls, the treated animals showed a significant improvement of clinical and neurophysiological parameters. After 3 months of observation, the collagen content of the transection site was reduced, and in the silicone series, the total number of myelinated axons 5 mm distal to the site of transection was increased, while the fiber diameter distribution was unchanged. PMID:1336302

  20. Platelet-rich plasma gel in combination with Schwann cells for repair of sciatic nerve injury.

    PubMed

    Ye, Fagang; Li, Haiyan; Qiao, Guangxi; Chen, Feng; Tao, Hao; Ji, Aiyu; Hu, Yanling

    2012-10-15

    Bone marrow mesenchymal stem cells were isolated from New Zealand white rabbits, culture-expanded and differentiated into Schwann cell-like cells. Autologous platelet-rich plasma and Schwann cell-like cells were mixed in suspension at a density of 1 × 10(6) cells/mL, prior to introduction into a poly (lactic-co-glycolic acid) conduit. Fabricated tissue-engineered nerves were implanted into rabbits to bridge 10 mm sciatic nerve defects (platelet-rich plasma group). Controls were established using fibrin as the seeding matrix for Schwann cell-like cells at identical density to construct tissue-engineered nerves (fibrin group). Twelve weeks after implantation, toluidine blue staining and scanning electron microscopy were used to demonstrate an increase in the number of regenerating nerve fibers and thickness of the myelin sheath in the platelet-rich plasma group compared with the fibrin group. Fluoro-gold retrograde labeling revealed that the number of Fluoro-gold-positive neurons in the dorsal root ganglion and the spinal cord anterior horn was greater in the platelet-rich plasma group than in the fibrin group. Electrophysiological examination confirmed that compound muscle action potential and nerve conduction velocity were superior in the platelet-rich plasma group compared with the fibrin group. These results indicate that autologous platelet-rich plasma gel can effectively serve as a seeding matrix for Schwann cell-like cells to construct tissue-engineered nerves to promote peripheral nerve regeneration. PMID:25538751