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  1. Genetics Home Reference: giant axonal neuropathy

    ... in giant axonal neuropathy: new insights into disease mechanisms. Muscle Nerve. 2012 Aug;46(2):246-56. ... with a qualified healthcare professional . About Genetics Home Reference Site Map Contact Us Selection Criteria for Links ...

  2. Axonal neuropathy associated with monoclonal gammopathy of undetermined significance

    GORSON, K.; Ropper, A.

    1997-01-01

    OBJECTIVE—The neuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) is typically a predominantly demyelinating process that may have additional features of axonal degeneration. Sixteen patients with MGUS and a pure or predominantly axonal neuropathy are reported and compared with 20 consecutive patients with demyelinating neuropathy and MGUS who were seen during the same period.
METHODS—Retrospective review of a consecutive series of patients w...

  3. Giant axonal neuropathy: observations on a further patient.

    Donaghy, M; Brett, E M; Ormerod, I E; King, R H; Thomas, P. K.

    1988-01-01

    A further child with giant axonal neuropathy (GAN), abnormally curly hair and consanguineous parents is described. Of the 19 patients with GAN so far reported in the literature, six, including the present patient, have resulted from consanguineous marriages. This makes autosomal recessive inheritance of GAN highly probable. Our patient also exhibited cerebellar ataxia and signs of pyramidal tract damage; magnetic resonance brain imaging demonstrated abnormalities within the cerebellar and cer...

  4. Axonal Transport Impairment in Chemotherapy-Induced Peripheral Neuropathy

    Gabriella Nicolini

    2015-08-01

    Full Text Available Chemotherapy-Induced Peripheral Neuropathy (CIPN is a dose-limiting side effect of several antineoplastic drugs which significantly reduces patients’ quality of life. Although different molecular mechanisms have been investigated, CIPN pathobiology has not been clarified yet. It has largely been recognized that Dorsal Root Ganglia are the main targets of chemotherapy and that the longest nerves are the most damaged, together with fast axonal transport. Indeed, this bidirectional cargo-specific transport has a pivotal role in neuronal function and its impairment is involved in several neurodegenerative and neurodevelopmental diseases. Literature data demonstrate that, despite different mechanisms of action, all antineoplastic agents impair the axonal trafficking to some extent and the severity of the neuropathy correlates with the degree of damage on this bidirectional transport. In this paper, we will examine the effect of the main old and new chemotherapeutic drug categories on axonal transport, with the aim of clarifying their potential mechanisms of action, and, if possible, of identifying neuroprotective strategies, based on the knowledge of the alterations induced by each drugs.

  5. Axon Transport and Neuropathy: Relevant Perspectives on the Etiopathogenesis of Familial Dysautonomia.

    Tourtellotte, Warren G

    2016-03-01

    Peripheral neuropathies are highly prevalent and are most often associated with chronic disease, side effects from chemotherapy, or toxic-metabolic abnormalities. Neuropathies are less commonly caused by genetic mutations, but studies of the normal function of mutated proteins have identified particular vulnerabilities that often implicate mitochondrial dynamics and axon transport mechanisms. Hereditary sensory and autonomic neuropathies are a group of phenotypically related diseases caused by monogenic mutations that primarily affect sympathetic and sensory neurons. Here, I review evidence to indicate that many genetic neuropathies are caused by abnormalities in axon transport. Moreover, in hereditary sensory and autonomic neuropathies. There may be specific convergence on gene mutations that disrupt nerve growth factor signaling, upon which sympathetic and sensory neurons critically depend. PMID:26724390

  6. Burning feet in polycythemia vera – peripheral sensorimotor axonal neuropathy with erythromelalgia

    Wollina U

    2015-02-01

    Full Text Available Uwe Wollina Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, Dresden, Germany Abstract: Polycythemia vera is a rare myeloproliferative disease. Cutaneous symptoms are uncommon. We report about a 72-year-old female patient with JAK2V617F-positive polycythemia who developed peripheral sensorimotor axonal neuropathy and erythromelalgia. Possible causes and treatment are discussed. Keywords: bone marrow diseases, myeloproliferative diseases, JAK2 mutations, burning sensations, peripheral neuropathy

  7. Sympathetic skin response--a method of assessing unmyelinated axon dysfunction in peripheral neuropathies.

    Shahani, B T; Halperin, J J; Boulu, P; Cohen, J.

    1984-01-01

    The sympathetic skin response (SSR) was measured in 33 patients with peripheral neuropathies and in 30 normal control subjects. Abnormalities of the response were correlated with clinical, pathologic, and EMG observations. The response was usually absent in axonal neuropathies, but present in demyelinating disorders. Abnormalities of the sympathetic skin response did not correlate well with clinical evidence of dysautonomia, but were a reliable indicator of disorders affecting unmyelinated ax...

  8. Clinical features and molecular modelling of novel MPZ mutations in demyelinating and axonal neuropathies

    Mandich, Paola; Fossa, Paola; Capponi, Simona; Geroldi, Alessandro; Acquaviva, Massimo; Gulli, Rossella; Ciotti, Paola; MANGANELLI, FIORE; Grandis, Marina; Bellone, Emilia

    2009-01-01

    Mutations in the myelin protein zero (MPZ) gene have been associated with different Charcot–Marie–Tooth disease (CMT) phenotypes, including classical demyelinating CMT1B and the axonal form of the disease (CMT2). The MPZ role in the pathogenesis of both demyelinating and axonal inherited neuropathies was evaluated in the Italian population by screening a cohort of 214 patients with CMT1 or CMT2. A MPZ mutation frequency of 7.9% in demyelinating cases and of 4.8% in axonal cases was observed. ...

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

    ... neuromyotonia is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles ... caused by damage to a particular part of peripheral nerves called axons , which are the extensions of nerve ...

  10. gamma-Diketone neuropathy: axon atrophy and the role of cytoskeletal protein adduction.

    LoPachin, Richard M; DeCaprio, Anthony P

    2004-08-15

    Multifocal giant neurofilamentous axonal swellings and secondary distal degeneration have been historically considered the hallmark features of gamma-diketone neuropathy. Accordingly, research conducted over the past 25 years has been directed toward discerning mechanisms of axonal swelling. However, this neuropathological convention has been challenged by recent observations that swollen axons were an exclusive product of long-term 2.5-hexanedione (HD) intoxication at lower daily dose-rates (e.g., 175 mg/kg/day); that is, higher HD dose-rates (e.g., 400 mg/kg/day) produced neurological deficits in the absence of axonal swellings. The observation that neurological toxicity can be expressed without axonal swelling suggests that this lesion is not an important pathophysiological event. Instead, several research groups have now shown that axon atrophy is prevalent in nervous tissues of laboratory animals intoxicated over a wide range of HD dose-rates. The well-documented nerve conduction defects associated with axon atrophy, in conjunction with the temporal correspondence between this lesion and the onset of neurological deficits, strongly suggest that atrophy has pathophysiological significance. In this commentary, we present evidence that supports a pathognomonic role for axon atrophy in gamma-diketone neuropathy and suggests that the functional consequences of this lesion mediate the corresponding neurological toxicity. Previous research has demonstrated that HD interacts with proteins via formation of pyrrole adducts. We therefore discuss the possibility that this chemical process is essential to the mechanism of atrophy. Evidence presented in this review suggests that "distal axonopathy" is an inaccurate classification and future nosological schemes should be based on the apparent primacy of axon atrophy. PMID:15289087

  11. Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase

    Single doses of organophosphorus compounds (OP) which covalently inhibit neuropathy target esterase (NTE) can induce lower-limb paralysis and distal damage in long nerve axons. Clinical signs of neuropathy are evident 3 weeks post-OP dose in humans, cats and chickens. By contrast, clinical neuropathy in mice following acute dosing with OPs or any other toxic compound has never been reported. Moreover, dosing mice with ethyloctylphosphonofluoridate (EOPF) - an extremely potent NTE inhibitor - causes a different (subacute) neurotoxicity with brain oedema. These observations have raised the possibility that mice are intrinsically resistant to neuropathies induced by acute toxic insult, but may incur brain oedema, rather than distal axonal damage, when NTE is inactivated. Here we provide the first report that hind-limb dysfunction and extensive axonal damage can occur in mice 3 weeks after acute dosing with a toxic compound, bromophenylacetylurea. Three weeks after acutely dosing mice with neuropathic OPs no clinical signs were observed, but distal lesions were present in the longest spinal sensory axons. Similar lesions were evident in undosed nestin-cre:NTEfl/fl mice in which NTE had been genetically-deleted from neural tissue. The extent of OP-induced axonal damage in mice was related to the duration of NTE inactivation and, as reported in chickens, was promoted by post-dosing with phenylmethanesulfonylfluoride. However, phenyldipentylphosphinate, another promoting compound in chickens, itself induced in mice lesions different from the neuropathic OP type. Finally, EOPF induced subacute neurotoxicity with brain oedema in both wild-type and nestin-cre:NTEfl/fl mice indicating that the molecular target for this effect is not neural NTE.

  12. Burning feet in polycythemia vera – peripheral sensorimotor axonal neuropathy with erythromelalgia

    Wollina U

    2015-01-01

    Uwe Wollina Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, Dresden, Germany Abstract: Polycythemia vera is a rare myeloproliferative disease. Cutaneous symptoms are uncommon. We report about a 72-year-old female patient with JAK2V617F-positive polycythemia who developed peripheral sensorimotor axonal neuropathy and erythromelalgia. Possible causes and treatment are discussed. Keywords: bone marrow diseases, myeloproliferative diseases, JAK2 mut...

  13. Association between acute motor axonal neuropathy and septic shock due to Acinetobacter baumannii.

    Toscani, Lucia; Guarducci, Diletta; Matà, Sabrina; Furlan, Tiziana; Ballo, Piercarlo

    2015-12-01

    In this report, we describe a case of acute motoral axonal neuropathy (AMAN) following septic shock due to Acinetobacter baumannii. The aetiology of AMAN is still not fully clarified. An association with a potential infection by Campylobacter jejuni, resulting in stimulation of autoimmune response against gangliosides mediated by a phenomenon of molecular mimicry, is believed to play a major role. Since the lipopolysaccharide of A. baumannii has a structure that is similar to that of C. jejuni, we hypothesise that the infection by A. baumannii in our patient may have had a pathogenic role in the development of the neurological picture via a mechanism of molecular mimicry. PMID:26700086

  14. Giant axonal neuropathy-like disease in an Alexandrine parrot (Psittacula eupatria).

    Stent, Andrew; Gosbell, Matthew; Tatarczuch, Liliana; Summers, Brian A

    2015-09-01

    A chronic progressive neurological condition in an Alexandrine parrot (Psittacula eupatria) was manifest as intention tremors, incoordination, and seizure activity. Histology revealed large eosinophilic bodies throughout the central nervous system, and electron microscopy demonstrated that these bodies were greatly expanded axons distended by short filamentous structures that aggregated to form long strands. The presence of periodic acid-Schiff-positive material within the neuronal bodies of Purkinje cells and ganglionic neurons is another distinctive feature of this disease. The histological features of this case display some features consistent with giant axonal neuropathy as reported in humans and dogs. Based on investigation of the lineage in this case, an underlying inherited defect is suspected, but some additional factor appears to have altered the specific disease presentation in this bird. PMID:26330398

  15. Assessment of retinal ganglion cell damage in glaucomatous optic neuropathy: Axon transport, injury and soma loss.

    Nuschke, Andrea C; Farrell, Spring R; Levesque, Julie M; Chauhan, Balwantray C

    2015-12-01

    Glaucoma is a disease characterized by progressive axonal pathology and death of retinal ganglion cells (RGCs), which causes structural changes in the optic nerve head and irreversible vision loss. Several experimental models of glaucomatous optic neuropathy (GON) have been developed, primarily in non-human primates and, more recently and commonly, in rodents. These models provide important research tools to study the mechanisms underlying glaucomatous damage. Moreover, experimental GON provides the ability to quantify and monitor risk factors leading to RGC loss such as the level of intraocular pressure, axonal health and the RGC population. Using these experimental models we are able to gain a better understanding of GON, which allows for the development of potential neuroprotective strategies. Here we review the advantages and disadvantages of the relevant and most often utilized methods for evaluating axonal degeneration and RGC loss in GON. Axonal pathology in GON includes functional disruption of axonal transport (AT) and structural degeneration. Horseradish peroxidase (HRP), rhodamine-B-isothiocyanate (RITC) and cholera toxin-B (CTB) fluorescent conjugates have proven to be effective reporters of AT. Also, immunohistochemistry (IHC) for endogenous AT-associated proteins is often used as an indicator of AT function. Similarly, structural degeneration of axons in GON can be investigated via changes in the activity and expression of key axonal enzymes and structural proteins. Assessment of axonal degeneration can be measured by direct quantification of axons, qualitative grading, or a combination of both methods. RGC loss is the most frequently quantified variable in studies of experimental GON. Retrograde tracers can be used to quantify RGC populations in rodents via application to the superior colliculus (SC). In addition, in situ IHC for RGC-specific proteins is a common method of RGC quantification used in many studies. Recently, transgenic mouse models

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

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

    2016-05-31

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

  17. γ-diketone central neuropathy: quantitative morphometric analysis of axons in rat spinal cord white matter regions and nerve roots

    A quantitative analytical method was used to measure myelinated axon morphometric parameters (e.g., axon area, ratio of axon area/fiber area, and index of circularity) in rat nervous tissue during intoxication with 2,5-hexanedione (HD). Parameters were assessed in nerve roots (dorsal and ventral) and in ascending (gracile fasciculus and spinocerebellar tract) and descending (corticospinal and rubrospinal tracts) spinal cord white matter tracts (L4-L5) of rats intoxicated with HD at two different daily dose-rates (175 or 400 mg HD/kg/day, gavage). For each dose-rate, tissue was sampled at four neurological endpoints: unaffected, slight, moderate, and severe toxicity, as determined by gait analysis and measurements of grip strength. Results indicate that, regardless of the HD dose-rate, axon atrophy (reduced axon area) was a widespread, abundant effect that developed in concert with neurological deficits. The atrophy response occurred contemporaneously in both ascending and descending spinal tracts, which suggests that loss of caliber developed simultaneously along the proximodistal axon axis. In contrast, swollen axons were a numerically small component and were present in nerve roots and spinal tracts only during subchronic intoxication at the lower HD dose-rate (i.e., 175 mg/kg/day). Intoxication at the higher dose-rate (400 mg/kg/day) produced neurological deficits in the absence of axonal swellings. These observations in conjunction with our previous studies of HD-induced peripheral neuropathy (Toxicol. Appl. Pharmacol. 135 (1995) 58; and Toxicol. Appl. Pharmacol. 165 (2000) 127) indicate that axon atrophy, and not axonal swelling, is a primary neuropathic phenomenon

  18. Sensomotor axonal peripheral neuropathy as a first complication of polycythemia rubra vera: A report of 3 cases

    Mihalj, Mario; Titlić, Marina; BONACIN, DAMIR; Đogaš, Zoran

    2013-01-01

    Patient: Female, 64 Final Diagnosis: Polycythemia rubra vera Symptoms: Burning pain • cramps • hypesthesia • itching • paresthesia Medication: — Clinical Procedure: — Specialty: Neurology Objective: Unusual clinical course Background: The association between polycythemia vera and peripheral neuropathy has been described previously but only as a late complication and only with sensory axonal polyneuropathy. We presume the cause of polyneuropathy was hypoxia due to higher blood viscosity and dy...

  19. Acute Motor Axonal Neuropathy (Aman) With Motor Conduction Blocks In Childhood; Case Report.

    Yildirim, Serhan; Adviye, Rahşan; Gül, Hakan Levent; Türk Börü, Ülkü

    2016-01-01

    Objective Acute motor axonal neuropathy (AMAN), characterized with decreased compound muscle action potentials (CMAP) and absence of demyelinating findings in electrophysiological studies, is a subtype of Guillain-Barre Syndrome (GBS). A 4 yr-old male patient presented with ascending weakness, dysarthria and dysphagia to İstanbul Dr. Lütfi Kırdar Kartal Training and Research Hospital Neurology outpatient for three days to in 2012. Dysphonia, restricted eye movements, flaccid tetraplegia and areflexia were found in neurological examination. There were motor conduction blocks in all peripheral nerves in electrophysiological studies.According to these findings the patient was diagnosed as Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP). Reduction of CMAP amplitudes in posterior tibial nerve, absence of CMAPs in median, ulnar and peroneal nerves and loss of motor conduction blocks were found in following electrophysiological studies. According to these findings, patient was diagnosed as AMAN. Motor conduction blocks may appear in early stage of AMAN and they disappear in later examinations. That's why electrophysiological studies must be repeated in patients with GBS. PMID:27057191

  20. Gamma-Diketone central neuropathy: quantitative analyses of cytoskeletal components in myelinated axons of the rat rubrospinal tract.

    Lopachin, Richard M; Jortner, Bernard S; Reid, Maria L; Monir, Alim

    2005-12-01

    Loss of axon caliber is a primary component of gamma-diketone neuropathy [LoPachin RM, DeCaprio AP. gamma-Diketone central neuropathy: axon atrophy and the role of cytoskeletal protein adduction. Toxicol Appl Pharmacol 2004;199:20-34]. It is possible that this effect is mediated by changes in the density of cytoskeletal components and corresponding spatial relationships. To examine this possibility, morphometric methods were used to quantify the effects of 2,5-hexanedione (HD) intoxication on neurofilament-microtubule densities and nearest neighbor distances in myelinated rubrospinal axons. Rats were exposed to HD at one of two daily dose-rates (175 or 400 mg/kg per day, gavage) until a moderate level of neurotoxicity was achieved (99 or 21 days of intoxication, respectively) as determined by gait analysis and measurements of hindlimb grip strength. Results indicate that, regardless of dose-rate, HD intoxication did not cause changes in axonal neurofilament (NF) density, but did significantly increase microtubule (MT) density. No consistent alterations in interneurofilament or NF-MT distances were detected by ultrastructural morphometric analyses. These data suggest that the axon atrophy induced by HD was not mediated by major disruptions of stationary cytoskeletal organization. Recent biochemical studies of spinal cord from HD intoxicated rats showed that, although the NF protein content in the stationary cytoskeleton (polymer fraction) was not affected, the mobile subunit pool was depleted substantially [LoPachin RM, He D, Reid ML, Opanashuk LA. 2,5-Hexanedione-induced changes in the monomeric neurofilament protein content of rat spinal cord fractions. Toxicol Appl Pharmacol 2004;198:61-73]. The stability of the polymer fraction during HD intoxication is consistent with the absence of significant ultrastructural modifications noted in the present study. Together, these findings implicate loss of mobile NF proteins as the primary mechanism of axon atrophy. PMID

  1. The neuropathic oesophagus. A radiographic and manometric study on the evolution of megaoesophagus in dogs with developing axonal neuropathy

    Dogs given the neurotoxin acrylamide develop peripheral neuropathy and megaoesophagus. Sequential radiographic and manometric studies on the oesophagus demonstrated that the initial abnormalities consisted of a progressive decrease in the proportion of swallows that initiated peristalsis and a gradual increase in oesophageal calibre. Regurgitation, peristaltic failure and oesophageal dilatation all appeared within three days. The eating behaviour and gait abnormalities quickly resolved on stopping the neurotoxin, but the oesophagus remained dilated for longer. Previous studies have suggested that the abnormalities present in dogs which are developing a distal axonal neuropathy or in some dogs with idiopathic megaoesophagus may be limited to the proprioceptive elements of the oesophageal innervation. The present study suggests that the progressive inefficiency in the transmission of swallows and changes in oesophageal calibre in dogs with evolving megaoesophagus may be a consequence of damage to these proprioceptive elements

  2. The instability of the BTB-KELCH protein Gigaxonin causes Giant Axonal Neuropathy and constitutes a new penetrant and specific diagnostic test

    Boizot, Alexia; Talmat-Amar, Yasmina; Morrogh, Deborah; Kuntz, Nancy; Halbert, Cecile; Chabrol, Brigitte; Houlden, Henry; Stojkovic, Tanya; Schulman, Brenda; Rautenstrauss, Bernd; Bomont, Pascale

    2014-01-01

    International audience BACKGROUND: The BTB-KELCH protein Gigaxonin plays key roles in sustaining neuron survival and cytoskeleton architecture. Indeed, recessive mutations in the Gigaxonin-encoding gene cause Giant Axonal Neuropathy (GAN), a severe neurodegenerative disorder characterized by a wide disorganization of the Intermediate Filament network. Growing evidences suggest that GAN is a continuum with the peripheral neuropathy Charcot-Marie-Tooth diseases type 2 (CMT2). Sharing similar...

  3. Clinical pathological and genetic analysis of 2 cases of mitochondrial myopathy presented as acute motor axonal neuropathy

    Hou-min YIN

    2014-06-01

    Full Text Available Background The main clinical manifestations of mitochondrial myopathy are chronic limb weakness and muscular soreness. Subclinical peripheral nerve injury is also reported, but acute axonal neuropathy.like syndrome concurrent with lactic acidosis is rare. In this paper the clinical features of 2 patients presenting as acute lactic acidosis and sudden muscle weakness were analyzed. Pathological changes and genetic mutations were detected.  Methods Electromyography (EMG and muscle biopsy were performed. Modified Gomori trichrome (MGT and succinodehydrogenase (SDH staining were used to identify pathological changes. Changes of ultra microstructure of muscular tissue were observed under electron microscope. Mitochondrial DNA (mtDNA full length sequencing was performed using 24 pairs of partially overlapping primers.  Results EMG showed a coexistence of neurogenic and myogenic changes. Dramatic decrease of motor nerve amplitude and moderately reduced sensory nerve amplitude were observed but nerve conduction velocity was normal in both patients. Impressive ragged red fibers were seen on MGT staining. Electron microscope showed dramatic mitochondrial abnormalities in Case 1 and paracrystaline inclusions in Case 2. mtDNA sequencing showed 3243A > G mutation in Case 1 and 8344A > G mutation in Case 2. Conclusions Mitochondrial myopathy can present as metabolic crisis like acute lactic acidosis, dyspnea and acute motor axonal neuropathy.like syndrome. It is a life.threatening phenotype that needs more attention. doi: 10.3969/j.issn.1672-6731.2014.06.007

  4. Factors predicting optic nerve axonal degeneration after methanol-induced acute optic neuropathy: a 2-year prospective study in 54 patients

    Zakharov, S.; Nurieva, O.; Kotíková, K.; Urban, P.; Navrátil, Tomáš; Pelclová, D.

    2016-01-01

    Roč. 147, č. 1 (2016), s. 251-261. ISSN 0026-9247 Institutional support: RVO:61388955 Keywords : methanol optic neuropathy * visual evoked potentials * axonal degeneration Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.222, year: 2014

  5. A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family.

    Abu-Rashid, M; Mahajnah, M; Jaber, L; Kornreich, L; Bar-On, E; Basel-Vanagaite, L; Soffer, D; Koenig, M; Straussberg, R

    2013-05-01

    Giant axonal neuropathy is a severe autosomal recessive neurodegenerative disorder of childhood that affects both the peripheral and central nervous systems. It is caused by mutations in the GAN gene linked to chromosome 16q24.1 At least 45 distinct disease-causing mutations have been identified throughout the gene in families of various ethnic origins, with different symptomatologies and different clinical courses. To date, no characteristic mutation or phenotype-genotype correlation has been established. We describe a novel missense mutation in four siblings born to consanguineous parents of Arab original with clinical and molecular features compatible with giant axonal neuropathy. The phenotype was characterized by a predominant motor and sensory peripheral neuropathies and severe skeletal deformities. PMID:23332420

  6. Toxic neuropathies

    Misra Usha

    2009-01-01

    Full Text Available 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.

  7. Peripheral neuropathy in the Twitcher mouse involves the activation of axonal caspase 3

    Ernesto R Bongarzone

    2011-10-01

    Full Text Available Infantile Krabbe disease results in the accumulation of lipid-raft-associated galactosylsphingosine (psychosine, demyelination, neurodegeneration and premature death. Recently, axonopathy has been depicted as a contributing factor in the progression of neurodegeneration in the Twitcher mouse, a bona fide mouse model of Krabbe disease. Analysis of the temporal-expression profile of MBP (myelin basic protein isoforms showed unexpected increases of the 14, 17 and 18.5 kDa isoforms in the sciatic nerve of 1-week-old Twitcher mice, suggesting an abnormal regulation of the myelination process during early postnatal life in this mutant. Our studies showed an elevated activation of the pro-apoptotic protease caspase 3 in sciatic nerves of 15- and 30-day-old Twitcher mice, in parallel with increasing demyelination. Interestingly, while active caspase 3 was clearly contained in peripheral axons at all ages, we found no evidence of caspase accumulation in the soma of corresponding mutant spinal cord motor neurons. Furthermore, active caspase 3 was found not only in unmyelinated axons, but also in myelinated axons of the mutant sciatic nerve. These results suggest that axonal caspase activation occurs before demyelination and following a dying-back pattern. Finally, we showed that psychosine was sufficient to activate caspase 3 in motor neuronal cells in vitro in the absence of myelinating glia. Taken together, these findings indicate that degenerating mechanisms actively and specifically mediate axonal dysfunction in Krabbe disease and support the idea that psychosine is a pathogenic sphingolipid sufficient to cause axonal defects independently of demyelination.

  8. Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy

    Tucci,A; Liu, Y. T.; Preza, E; Pitceathly, R. D.; Chalasani, A.; Plagnol, V.; Land, J. M.; Trabzuni, D.; Ryten, M.; Jaunmuktane, Z.; Reilly, M.M.; Brandner, S; Hargreaves, I.; Hardy, J.; Singleton, A B

    2013-01-01

    Objective Charcot-Marie Tooth disease (CMT) forms a clinically and genetically heterogeneous group of disorders. Although a number of disease genes have been identified for CMT, the gene discovery for some complex form of CMT has lagged behind. The association of neuropathy and optic atrophy (also known as CMT type 6) has been described with autosomaldominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylp...

  9. Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection

    Keppel Hesselink JM

    2013-09-01

    Full Text Available J M Keppel Hesselink Faculty of Medicine, University Witten/Herdecke, Germany Abstract: Chronic idiopathic axonal polyneuropathy is a frequent diagnosis in patients suffering from idiopathic polyneuropathy and neuropathic pain. No guidelines exist on how to treat these patients. To date, there are no results available from randomized clinical trials, and mostly classical neuropathic analgesics are prescribed, such as amitriptyline and gabapentine. However, the usefulness of these drugs is limited, as many patients remain in pain despite treatment, or suffer debilitating side effects. Palmitoylethanolamide (PEA is a new analgesic compound, tested in more than 4,000 patients in various clinical trials in a variety of patients suffering from various neuropathic pain states. It is available in Europe and the USA as a food supplement under the brand name PeaPure, and it is available for medical purposes in Italy and Spain under brand names Normast and Pelvilen. We present a case series of seven patients with an electrophysiological confirmed diagnosis of chronic idiopathic axonal polyneuropathy, suffering from neuropathic pains, mostly refractory to previous analgesics. In all these patients, PEA reduced pain significantly, without side effects. PEA can be administered in addition to other analgesics, without negative drug–drug interactions, or can be used as a stand-alone analgesic. Due to a favorable ratio between efficacy and safety, PEA should be considered more often as a treatment for neuropathic pain. Keywords: CIAP, polyneuropathy, treatment, neuropathic

  10. Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy [v2; ref status: indexed, http://f1000r.es/3am

    Lori Sames

    2014-04-01

    Full Text Available 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

  11. Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy [v1; ref status: indexed, http://f1000r.es/33n

    Lori Sames

    2014-04-01

    Full Text Available 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

  12. 急性运动轴索性神经病的研究进展%Research progress of acute motor axonal neuropathy

    张刚; 秦新月

    2014-01-01

    Acute motor axonal neuropathy (AMAN) is one of the main subtypes of Guillain-Barré syndrome (GBS), which presents with acute ascending flaccid paralysis like acute inflammatory demyelinating polyneuropathy (AIDP). But AMAN can be different with AIDP in clinical manifestation, immunopathogenesis, electrophysiology, serum antibody, prognosis, et al. This review focused on the research progress of AMAN.%急性运动轴索性神经病(AMAN)是吉兰-巴雷综合征(GBS)的主要亚型之一,与GBS主要亚型急性炎症性脱髓鞘性多发性神经病(AIDP)在临床表现、免疫病理生理机制、神经电生理检查、血清学抗体等方面均有不同。本文就AMAN相关研究进展做一综述。

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

    Nerve excitability (NE) testing is a sensitive method to test for peripheral neurotoxicity in humans,and may be more sensitive than compound nerve action potential (CNAP) or nerve conduction velocity (NCV).We used acrylamide to compare the NE and CNAP/NCV methods. Behavioral test...

  14. Inherited mitochondrial neuropathies.

    Finsterer, Josef

    2011-05-15

    Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations. MIDs in which polyneuropathy is an inconstant feature among others is the MELAS syndrome, MERRF syndrome, LHON, Mendelian PEO, KSS, Leigh syndrome, MNGIE, SANDO; MIRAS, MEMSA, AHS, MDS (hepato-cerebral form), IOSCA, and ADOA syndrome. In the majority of the cases polyneuropathy presents in a multiplex neuropathy distribution. Nerve conduction studies may reveal either axonal or demyelinated or mixed types of neuropathies. If a hereditary neuropathy is due to mitochondrial dysfunction, the management of these patients is at variance from non-mitochondrial hereditary neuropathies. Patients with mitochondrial hereditary neuropathy need to be carefully investigated for clinical or subclinical involvement of other organs or systems. Supportive treatment with co-factors, antioxidants, alternative energy sources, or lactate lowering agents can be tried. Involvement of other organs may require specific treatment. Mitochondrial neuropathies should be included in the differential diagnosis of hereditary neuropathies. PMID:21402391

  15. Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo - therapeutic potential for peripheral neuropathies: results of a randomised controlled trial

    Fleckenstein, Johannes; Sittl, Ruth; Averbeck, Beate; Lang, Philip M; Irnich, Dominik; Richard W Carr

    2013-01-01

    Background: Flupirtine is an analgesic with muscle-relaxing properties that activates Kv7 potassium channels. Kv7 channels are expressed along myelinated and unmyelinated peripheral axons where their activation is expected to reduce axonal excitability and potentially contribute to flupirtine’s clinical profile. Trial design: To investigate the electrical excitability of peripheral myelinated axons following orally administered flupirtine, in-vitro experiments on isolated peripheral nerve s...

  16. Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo - therapeutic potential for peripheral neuropathies: results of a randomised controlled trial

    Fleckenstein, Johannes; Sittl, Ruth; Averbeck, Beate; Lang, Philip M; Irnich, Dominik; Richard W Carr

    2013-01-01

    Background Flupirtine is an analgesic with muscle-relaxing properties that activates Kv7 potassium channels. Kv7 channels are expressed along myelinated and unmyelinated peripheral axons where their activation is expected to reduce axonal excitability and potentially contribute to flupirtine’s clinical profile. Trial design To investigate the electrical excitability of peripheral myelinated axons following orally administered flupirtine, in-vitro experiments on isolated peripheral nerve segme...

  17. Hereditary Neuropathies

    ... group of inherited disorders affecting the peripheral nervous system. The hereditary neuropathies are divided into four major subcategories: hereditary motor and sensory neuropathy, hereditary sensory neuropathy, hereditary motor neuropathy, and ...

  18. Anti-glycan antibodies halt axon regeneration in a model of Guillain Barrè Syndrome axonal neuropathy by inducing microtubule disorganization via RhoA-ROCK-dependent inactivation of CRMP-2.

    Rozés Salvador, Victoria; Heredia, Florencia; Berardo, Andrés; Palandri, Anabela; Wojnacki, Jose; Vivinetto, Ana L; Sheikh, Kazim A; Caceres, Alfredo; Lopez, Pablo H H

    2016-04-01

    Several reports have linked the presence of high titers of anti-Gg Abs with delayed recovery/poor prognosis in GBS. In most cases, failure to recover is associated with halted/deficient axon regeneration. Previous work identified that monoclonal and patient-derived anti-Gg Abs can act as inhibitory factors in an animal model of axon regeneration. Further studies using primary dorsal root ganglion neuron (DRGn) cultures demonstrated that anti-Gg Abs can inhibit neurite outgrowth by targeting gangliosides via activation of the small GTPase RhoA and its associated kinase (ROCK), a signaling pathway common to other established inhibitors of axon regeneration. We aimed to study the molecular basis of the inhibitory effect of anti-Gg abs on neurite outgrowth by dissecting the molecular dynamics of growth cones (GC) cytoskeleton in relation to the spatial-temporal analysis of RhoA activity. We now report that axon growth inhibition in DRGn induced by a well characterized mAb targeting gangliosides GD1a/GT1b involves: i) an early RhoA/ROCK-independent collapse of lamellipodia; ii) a RhoA/ROCK-dependent shrinking of filopodia; and iii) alteration of GC microtubule organization/and presumably dynamics via RhoA/ROCK-dependent phosphorylation of CRMP-2 at threonine 555. Our results also show that mAb 1B7 inhibits peripheral axon regeneration in an animal model via phosphorylation/inactivation of CRMP-2 at threonine 555. Overall, our data may help to explain the molecular mechanisms underlying impaired nerve repair in GBS. Future work should define RhoA-independent pathway/s and effectors regulating actin cytoskeleton, thus providing an opportunity for the design of a successful therapy to guarantee an efficient target reinnervation. PMID:26804001

  19. Diabetic Neuropathy

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

  20. Axoval neuropathy as initial manifestation of primary amyloidosis: report of a case submitted to bone marrow transplantation Neuropatia axonal como manifestação inicial de amiloidose primária: relato de caso submetido a transplante de medula óssea

    Orlando G. Povoas Barsottini; Adriano Arantes; Daniel Sigulem; José Mauro Kutner; Andreza Alice Feitosa Ribeiro; Luiz A. Moura; Nelson Hamerschlak

    2004-01-01

    Amyloidosis is a syndrome characterized by deposition of a highly insoluble protein material in the extracellular space that may affect several organs. It may be generalized and idiopathic (primary amyloidosis). We describe the case of a 48 years-old woman with axonal neuropathy associated with proteinuria, whose final investigation resulted in diagnosis of primary amyloidosis (AL). She was submitted to autologous bone marrow transplantation. We discuss some aspects related to diagnosis of ne...

  1. Sympathetic neuropathy in diabetes mellitus patients does not elicit Charcot osteoarthropathy

    Christensen, Tomas M; Simonsen, Lene; Holstein, Per E;

    2011-01-01

    neuropathy was done by the Neuropathy Disability Score and modified Neuropathy Symptom Score. Quantitation of autonomic neuropathy was done by measurements of local venoarteriolar sympathetic axon reflex in the feet and of heart rate variability during deep breathing and orthostatic challenge. RESULTS...

  2. Peripheral Neuropathy

    ... 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 ...

  3. Diagnostic approach to peripheral neuropathy

    Misra Usha

    2008-01-01

    Full Text Available Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG. EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG. Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.

  4. Axoval neuropathy as initial manifestation of primary amyloidosis: report of a case submitted to bone marrow transplantation Neuropatia axonal como manifestação inicial de amiloidose primária: relato de caso submetido a transplante de medula óssea

    Orlando G. Povoas Barsottini

    2004-09-01

    Full Text Available Amyloidosis is a syndrome characterized by deposition of a highly insoluble protein material in the extracellular space that may affect several organs. It may be generalized and idiopathic (primary amyloidosis. We describe the case of a 48 years-old woman with axonal neuropathy associated with proteinuria, whose final investigation resulted in diagnosis of primary amyloidosis (AL. She was submitted to autologous bone marrow transplantation. We discuss some aspects related to diagnosis of neuropathy and current treatment of AL.A amiloidose é uma síndrome caracterizada pela deposição no meio extracelular de material protéico altamente insolúvel e que pode afetar vários órgãos. Pode ocorrer como doença generalizada e pode ser idiopática (amiloidose primária. Descrevemos o caso de mulher de 48 anos com neuropatia axonal associada a proteinúria na qual a investigação final resultou no diagnóstico de amiloidose primária (AL. Foi submetida a transplante autólogo de medula óssea sem complicações. Discutiremos aspectos relacionados ao diagnóstico da neuropatia e do tratamento atual da AL.

  5. Peripheral neuropathy associated with mitochondrial disease in children.

    Menezes, Manoj P; Ouvrier, Robert A

    2012-05-01

    Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease. PMID:22435634

  6. Neuropathy of nitroimidazole radiosensitizers: clinical and pathological description

    The dose limiting toxicity of the nitroimidazole radiosensitizers is peripherial neuropathy. Improved pharmacology of newer drugs has eliminated the encephalopathy. Peripheral neuropathies are predominently mild to moderate paresthesias of both hands and feet. Subjective changes occur with or without minimal objective changes on neurologic exam. All of the neuropathies occurred within 30 days of the last drug dose and are of varible duration. Sural nerve biopsies from patients indicate progressive axonal degeneration affecting both large and small caliber myelinated fibers. Axonal damage appears to be more severe in the distal portion of the nerves. More data are needed for correlation of clinical and pathological changes

  7. Alcoholic neuropathy

    ... objects in the shoes Guarding the extremities to prevent injury from pressure Alcohol must be stopped to prevent the damage from ... The only way to prevent alcoholic neuropathy is not to drink excessive amounts of alcohol.

  8. Peripheral neuropathy

    Peripheral neuritis; Neuropathy - peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy ... Katirji B, Koontz D. Disorders of peripheral nerves. In: Daroff RB, ... Practice . 6th ed. Philadelphia, PA: Elsevier Saunders; 2012: ...

  9. Auditory Neuropathy

    ... field differ in their opinions about the potential benefits of hearing aids, cochlear implants, and other technologies for people with auditory neuropathy. Some professionals report that hearing aids and personal listening devices such as frequency modulation (FM) systems are ...

  10. Peripheral Neuropathy

    ... injury (trauma) to a nerve, tumors, toxins, autoimmune responses, nutritional deficiencies, alcoholism, medical procedures, and vascular and metabolic disorders. Acquired peripheral neuropathies are caused by systemic disease, trauma from external agents, or infections or autoimmune disorders ...

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

    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

  12. Critical illness neuropathy

    Vijayan J

    2005-01-01

    Full Text Available The neuromuscular syndrome of acute limb and respiratory weakness that commonly accompanies patients with multi-organ failure and sepsis constitutes critical illness polyneuropathy. It is a major cause of difficulty in weaning off the patient from the ventilator after respiratory and cardiac causes have been excluded. It is usually an axonal motor-sensory polyneuropathy, and is usually associated with or accompanied with a coma producing septic encephalopathy. The neuropathy is usually not apparent until the patient′s encephalopathy has peaked, and may be noted only when the brain dysfunction is resolving. Patients usually have a protracted hospital course complicated by multi-organ failure and the systemic inflammatory response syndrome. Elevated serum glucose levels and reduced albumin are risk factors for nerve dysfunction, as is prolonged intensive care unit stay. Polyneuropathy may develop after only one week of the systemic inflammatory response syndrome, but the frequency tends to correlate with the duration of the severe illness.

  13. Sympathetic vasoconstrictor nerve function in alcoholic neuropathy

    Jensen, K; Andersen, K; Smith, T;

    1984-01-01

    The peripheral sympathetic vasomotor nerve function was investigated in 18 male chronic alcoholics admitted for intellectual impairment or polyneuropathy. By means of the local 133Xenon washout technique, the sympathetic veno-arteriolar axon-reflex was studied. This normally is responsible for a 50...... (18% and 48% decrease respectively). However, in three patients with moderate neuropathy, and in one patient with no signs of neuropathy, this veno-arteriolar reflex was absent, indicating dysfunction of the peripheral sympathetic adrenergic nerve fibres. The three patients also showed a lesser degree...... alcohol comprise not only the peripheral sensory and motor nerve fibres, but also the thin pseudomotor and vasomotor nerves....

  14. Multifocal Motor Neuropathy

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

  15. Chronic obstructive pulmonary disease and peripheral neuropathy

    Gupta Prem

    2006-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death world-wide and a further increase in the prevalence as well as mortality of the disease is predicted for coming decades. There is now an increased appreciation for the need to build awareness regarding COPD and to help the thousands of people who suffer from this disease and die prematurely from COPD or its associated complication(s. Peripheral neuropathy in COPD has received scanty attention despite the fact that very often clinicians come across COPD patients having clinical features suggestive of peripheral neuropathy. Electrophysiological tests like nerve conduction studies are required to distinguish between axonal and demyelinating type of disorder that cannot be analyzed by clinical examination alone. However, various studies addressing peripheral neuropathy in COPD carried out so far have included patients with COPD having markedly varying baseline characteristics like severe hypoxemia, elderly patients, those with long duration of illness, etc. that are not uniform across the studies and make it difficult to interpret the results to a consistent conclusion. Almost one-third of COPD patients have clinical evidence of peripheral neuropathy and two-thirds have electrophysiological abnormalities. Some patients with no clinical indication of peripheral neuropathy do have electrophysiological deficit suggestive of peripheral neuropathy. The more frequent presentation consists of a polyneuropathy that is subclinical or with predominantly sensory signs, and the neurophysiological and pathological features of predominantly axonal neuropathy. The presumed etiopathogenic factors are multiple: chronic hypoxia, tobacco smoke, alcoholism, malnutrition and adverse effects of certain drugs.

  16. Nodes of Ranvier and Paranodes in Chronic Acquired Neuropathies

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

    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 per...

  17. Peptide mimetic of the S100A4 protein modulates peripheral nerve regeneration and attenuates the progression of neuropathy in myelin protein P0 null mice

    Moldovan, Mihai; Pinchenko, Volodymyr; Dmytriyeva, Oksana;

    2013-01-01

    disease), where the peptide attenuated the deterioration of nerve conduction, demyelination and axonal loss. From these results, S100A4 mimetics emerge as a possible means to enhance axonal sprouting and survival, especially in the context of demyelinating neuropathies with secondary axonal loss...

  18. Clinicopathological study of vasculitic peripheral neuropathy

    Rong-fang DONG

    2014-06-01

    Full Text Available Objective To summarize the clinical features and neuropathological characteristics in patients with vasculitic peripheral neuropathy (VPN. Methods Clinical manifestations, laboratory examination and neuromuscular biopsy characteristics of 11 patients with VPN were retrospectively analyzed. The lesion of nerve, muscle and skin was observed under optical and electron microscope. Immunohistochemical analyses were carried out to detect neurofilament (NF, myelin basic protein (MBP, peripheral myelin protein 22 (PMP22 and S-100 protein (S-100 and further observing the neuropathy of neuraxon, myelin sheath and Schwann cells, and to detect human leukocyte antigen DR (HLA-DR, CD68, CD3 and CD20 to observe inflammatory cell infiltration. Immunofluorescent staining was used to detect the deposition of IgA, IgM, IgG and addiment C3 on vascular wall. The staining of periodic acid-Schiff (PAS, NADH-tetrazolium reductase (NADH-TR and modified Gomori trichrome (MGT were used to judge the myopathy. Results 1 Angiopathies were mainly manifested by small vessels of epineurium and perineurium, and infiltrated inflammatory cells were mainly CD3 + T cells. Three patients had active vasculitis, and 8 patients had non-active vasculitis. Among these 8 patients, 4 patients mainly presented fibrous obliteration of blood vessel, with slight inflammatroy cell infiltration, and the other 4 patients mainly showed perivascular inflammation. 2 Neuropathy: 6 patients had axon degeneration, and 5 patients had axon degeneration associated with demyelination. All of them demonstrated a reduction in myelinated fibers, mainly large diameter myelinated fibers, even on end-stage. 3 Muscle biopsy showed neurogenic atrophy. 4 Clinicopathologic diagnosis: among these 11 patients, 8 patients were diagnosed as systemic vasculitic peripheral neuropathy (SVPN, among whom 5 patients were diagnosed as primary systemic vasculitis [including 1 patient as Churg-Strauss syndrome (CSS, 2 patients as

  19. Updates in diabetic peripheral neuropathy

    Juster-Switlyk, Kelsey; Smith, A. Gordon

    2016-01-01

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

  20. Streptozotocin induced diabetes as a model of phrenic nerve neuropathy in rats.

    Rodrigues Filho, Omar Andrade; Fazan, Valéria Paula Sassoli

    2006-03-15

    Phrenic neuropathies are increasingly recognized in peripheral neuropathies but reports on experimental models of the phrenic nerves diabetic neuropathy are scanty. In the present study, we investigated the phrenic nerve neuropathy, due to experimental diabetes induced by streptozotocin (STZ) and the evolution of this neuropathy in diabetic rats treated with insulin. Proximal and distal segments of the left and right phrenic nerves were morphologically and morphometrically evaluated, from rats rendered diabetic for 12 weeks, by injection of STZ. Control rats received vehicle. Treated rats received a single subcutaneous injection of insulin on a daily basis. The nerves were prepared for light microcopy study by means of conventional techniques. Morphometry was carried out with the aid of computer software. The phrenic nerves of diabetic rats showed smaller myelinated axon diameters compared to controls. The g ratio was significantly smaller for myelinated fibers from diabetic rats compared to controls. Insulin treatment prevented these alterations. Histograms of size distribution for myelinated fibers and axons from control rats were bimodal. For diabetic animals, the myelinated fiber histogram was bimodal while the axon distribution turned to be unimodal. Insulin treatment also prevented these alterations. Our results confirm the phrenic nerve neuropathy in this experimental model of diabetes and suggest that conventional insulin treatment was able to prevent and/or correct the myelinated axon commitment by diabetes. PMID:16125783

  1. Entrapment neuropathies III: lower limb.

    Beltran, Luis S; Bencardino, Jenny; Ghazikhanian, Varand; Beltran, Javier

    2010-11-01

    Clinicians frequently encounter compressive neuropathies of the lower extremity. The clinical history and physical examination, along with electrodiagnostic testing and imaging studies, lead to the correct diagnosis. The imaging characteristics of the compression neuropathies can include acute and chronic changes in the nerves and the muscles they innervate. We provide a detailed review of compression neuropathies of the lower extremity with an emphasis on magnetic resonance (MR) imaging characteristics. We discuss the clinical presentation, etiology, anatomical location, and MR imaging appearance of these neuropathies, including the piriformis syndrome, iliacus syndrome, saphenous neuropathy, obturator neuropathy, lateral femoral cutaneous neuropathy (meralgia paresthetica), proximal tibial neuropathy, common peroneal neuropathy, deep peroneal neuropathy, superficial peroneal neuropathy, tarsal tunnel syndrome, Baxter's neuropathy, jogger's foot, sural neuropathy, and Morton's neuroma. PMID:21072728

  2. MicroRNA 146a locally mediates distal axonal growth of dorsal root ganglia neurons under high glucose and sildenafil conditions.

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

    2016-08-01

    Axonal loss contributes to induction of diabetic peripheral neuropathy. Sildenafil, a phosphodiesterase type 5 inhibitor, ameliorates neurological dysfunction in diabetic peripheral neuropathy. However, the direct effect of high glucose and sildenafil on axonal growth has not been extensively investigated. Using rat primary dorsal root ganglia (DRG) neurons cultured in a microfluidic chamber, we investigated the effect of axonal application of high glucose and sildenafil on distal axonal growth. We found that axonal, but not cell body, application of high glucose locally inhibited distal axonal growth. However, axonal application of sildenafil overcame high glucose-reduced axonal growth. Quantitative real-time RT-PCR (qRT-PCR) and Western blot analysis of distal axonal samples revealed that high glucose reduced axonal miR-146a levels and substantially increased miR-146a target genes, IRAK1 and TRAF6 in the axon. In contrast, sildenafil significantly reversed high glucose-reduced miR-146a levels and high glucose-increased IRAK1 and TRAF6. Gain- and loss-of function of miR-146a in DRG neurons revealed that miR-146a mediated the local effect of high glucose on the distal axonal growth. These in vitro data provide new insights into molecular mechanisms of diabetic peripheral neuropathy. PMID:27167084

  3. Computing along the axon

    Chen Haiming; Tseren-Onolt Ishdorj; Gheorghe Pǎun

    2007-01-01

    A special form of spiking neural P systems, called axon P systems, corresponding to the activity of Ranvier nodes of neuron axon, is considered and a class of SN-like P systems where the computation is done along the axon is introduced and their language generative power is investigated.

  4. Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease.

    Pitceathly, Robert D S

    2012-09-11

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6, encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8, might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN).

  5. Fcγ receptor-mediated inflammation inhibits axon regeneration.

    Gang Zhang

    Full Text Available Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

  6. Brachial plexus neuropathy

    Hubka, Michael J; King, Laurie; Cassidy, J. David; Donat, JR

    1992-01-01

    Branchial plexus neuropathy is characterized by acute onset of intense pain in the shoulder or arm followed shortly by focal muscle weakness. This presentation may mislead the clinician into diagnosing shoulder or cervical spine pathology. Although brachial plexus neuropathy is not common, it should be considered in the differential diagnosis of pain and weakness of the arm. We present a patient with brachial plexus neuropathy who was originally misdiagnosed as having a cervical disc herniation.

  7. Histological, Scanning And Transmission Electron Microscopic Studies On The Possible Protective Role Of Ginger Extract Against AcrylamideInduced Intestinal Damage In Mice

    Hala Galal El-Tantawi

    2007-12-01

    Full Text Available Objective: This study was carried out to evaluate the protective effect of ginger Zingeber officinale extract (ZOE against the acrylamide (AC which is an industrial chemical used in water treatment and it is synthesized during cooking of starch food at high temperature. Method: Thirty adult male albino mice, each weighs 20-25 g were divided into three groups (10 mice/group: (Icontrol group. (IIacrylamide treated group. (III acrylamide & ginger group. Acrylamide was given to experimental animals in the drinking water at a non-lethal dose of 200 p.p.m for 10 weeks (3 days/week. Ginger extract was orally administrated at 50 mg/L (~5 ml/day for 10 weeks (3 days/week. The ileum samples were collected for light microscope study and for scanning and transmission electron microscope examination. Results: This study revealed that acrylamide induces pathological changes of the ileum of the treated mice specially the absorptive epithelial cells. The scanning electron microscopic study revealed damage of the ileal villi, some red blood corpuscles appeared at the site of damage. The transmission electron microscopic examination clearly demonstrated degeneration of most cell organelles as mitochondria, deterioration and degranulation of the rough endoplasmic reticulum, dilatation of Golgi apparatus. Conclusion: The administration of ginger extract decreased the histological alterations and ensuring the anti-inflammatory, and antitoxic effects of ZOE at its chosen dosage level

  8. The relationship of nerve fibre pathology to sensory function in entrapment neuropathy

    Schmid, Annina B.; Bland, Jeremy D. P.; Bhat, Manzoor A.; Bennett, David L. H.

    2014-01-01

    Surprisingly little is known about the impact of entrapment neuropathy on target innervation and the relationship of nerve fibre pathology to sensory symptoms and signs. Carpal tunnel syndrome is the most common entrapment neuropathy; the aim of this study was to investigate its effect on the morphology of small unmyelinated as well as myelinated sensory axons and relate such changes to somatosensory function and clinical symptoms. Thirty patients with a clinical and electrophysiological diag...

  9. Genetically determined optic neuropathies

    Milea, Dan; Amati-Bonneau, Patrizia; Reynier, Pascal;

    2010-01-01

    The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.......The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions....

  10. Propylthiouracil and peripheral neuropathy

    Valentina Van Boekel

    1992-06-01

    Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

  11. [Immune-mediated neuropathies].

    Stoll, G; Reiners, K

    2016-08-01

    The Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are the most common immune-mediated polyneuropathies, which can show variable clinical and electrophysiological manifestations. Rarer immune-mediated neuropathies encompass paraproteinemic neuropathies (PPN), multifocal motor neuropathy (MMN) and vasculitic neuropathies. The diagnosis usually relies on the history of symptom evolution, distribution of nerve dysfunction and particularly on characteristic features in nerve conduction studies, aided by cerebrospinal fluid (CSF) examination and nerve biopsy findings. The therapeutic toolbox encompasses corticosteroids, immunoglobulins and plasmapheresis often accompanied by long-term immunosuppression. It is important to note that immune-mediated neuropathies selectively respond to treatment and contraindications need to be considered. Despite treatment a considerable number of patients suffer from permanent neurological deficits. PMID:27474733

  12. Motor Axon Pathfinding

    Bonanomi, Dario; Pfaff, Samuel L

    2010-01-01

    Motor neurons are functionally related, but represent a diverse collection of cells that show strict preferences for specific axon pathways during embryonic development. In this article, we describe the ligands and receptors that guide motor axons as they extend toward their peripheral muscle targets. Motor neurons share similar guidance molecules with many other neuronal types, thus one challenge in the field of axon guidance has been to understand how the vast complexity of brain connection...

  13. Medical management of hereditary optic neuropathies

    ChiaraLa Morgia

    2014-07-01

    Full Text Available Hereditary optic neuropathies are diseases of the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e. the maternally inherited Leber’s Hereditary Optic Neuropathy (LHON and Dominant Optic Atrophy (DOA. They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1 and 14484/ND6 for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone. Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising venue that still needs to be validated.

  14. Inherited peripheral neuropathies due to mitochondrial disorders.

    Cassereau, J; Codron, P; Funalot, B

    2014-05-01

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

  15. [Chemotherapy induced peripheral neuropathy].

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

    2013-11-01

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

  16. Ciliary neurotrophic factor activates NF-κB to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents

    Saleh, Ali; Roy Chowdhury, Subir K.; Smith, Darrel R.; Balakrishnan, Savitha; Tessler, Lori; Martens, Corina; Morrow, Dwane; Schartner, Emily; Frizzi, Katie E.; Calcutt, Nigel A.; Fernyhough, Paul

    2012-01-01

    Diabetes causes mitochondrial dysfunction in sensory neurons that may contribute to peripheral neuropathy. Ciliary neurotrophic factor (CNTF) promotes sensory neuron survival and axon regeneration and prevents axonal dwindling, nerve conduction deficits and thermal hypoalgesia in diabetic rats. In this study, we tested the hypothesis that CNTF protects sensory neuron function during diabetes through normalization of impaired mitochondrial bioenergetics. In addition, we investigated whether th...

  17. HIV peripheral neuropathy.

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

    2013-01-01

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

  18. Leprosy neuropathy: clinical presentations.

    Nascimento, Osvaldo J M

    2013-09-01

    Leprosy is a chronic infectious peripheral neuropathy caused by Mycobacterium leprae. The different clinical presentations of the disease are determined by the quality of the host immune response. Early detection of leprosy and treatment by multidrug therapy are the most important steps in preventing deformity and disability. Thus the early recognition of the clinical leprosy presentation is essential. Mononeuritis, mononeuritis multiplex (MM), polyneuritis (MM summation) are the most frequent. The frequent anesthetic skin lesions are absent in the pure neuritic leprosy presentation form. Isolated peripheral nerve involvement is common, including the cranial ones. Arthritic presentation is occasionally seen, usually misdiagnosed as rheumatoid arthritis. Attention should be given to autonomic dysfunctions in leprosy. There are clinical presentations with severe neuropathic pain - painful small-fiber neuropathy. Leprous late-onset neuropathy (LLON) clinical presentation should be considered facing a patient who develop an inflammatory neuropathy many years after a previous skin leprosy treatment. PMID:24141500

  19. Motor axon loss is associated with hand dysfunction in Charcot-Marie-Tooth disease 1a.

    Videler, A.J.; Dijk, J.P. van; Beelen, A.; Visser, M. de; Nollet, F.; Schaik, I.N. van

    2008-01-01

    BACKGROUND: Charcot Marie Tooth type 1a (CMT1a) is a primarily demyelinating neuropathy, characterized by slowly progressive muscle weakness, atrophy, and sensory loss, and is most pronounced in both feet and hands. There is increasing evidence that muscle weakness is determined by motor axonal dysf

  20. Neurotrophic factors and their receptors in human sensory neuropathies.

    Anand, Praveen

    2004-01-01

    Neurotrophic factors may play key roles in pathophysiological mechanisms of human neuropathies. Nerve growth factor (NGF) is trophic to small-diameter sensory fibers and regulates nociception. This review focuses on sensory dysfunction and the potential of neurotrophic treatments. Genetic neuropathy. Mutations of the NGF high-affinity receptor tyrosine kinase A (Trk A) have been found in congenital insensitivity to pain and anhidrosis; these are likely to be partial loss-of-function mutations, as axon-reflex vasodilatation and sweating can be elicited albeit reduced, suggesting rhNGF could restore nociception in some patients. Leprous neuropathy. Decreased NGF in leprosy skin may explain cutaneous hypoalgesia even with inflammation and rhNGF may restore sensation, as spared nerve fibers show Trk A-staining. Diabetic neuropathy. NGF is depleted in early human diabetic neuropathy skin, in correlation with dysfunction of nociceptor fibers. We proposed rhNGF prophylaxis may prevent diabetic foot ulceration. Clinical trials have been disappointed, probably related to difficulty delivering adequate doses and need for multiple trophic factors. NGF and glial cell line-derived neurotrophic factor (GDNF) are both produced by basal keratinocytes and neurotrophin (NT-3) by suprabasal keratinocytes: relative mRNA expression was significantly lower in early diabetic neuropathy skin compared to controls, for NGF (P 0.05). Posttranslational modifications of mature and pro-NGF may also affect bioactivity and immunoreactivity. A 53 kD band that could correspond to a prepro-NGF-like molecule was reduced in diabetic skin. Traumatic neuropathy and pain. While NGF levels are acutely reduced in injured nerve trunks, neuropathic patients with chronic skin hyperalgesia and allodynia show marked local increases of NGF levels; here anti-NGF agents may provide analgesia. Physiological combinations of NGF, NT-3 and GDNF, to mimic a 'surrogate target organ', may provide a novel 'homeostatic

  1. Unilateral Acute Anterior Ischemic Optic Neuropathy in a Patient with an Already Established Diagnosis of Bilateral Optic Disc Drusen

    Ziya Ayhan; Aylin Yaman; Meltem Söylev Bajin; Osman Saatci, A

    2015-01-01

    Optic disc drusen (ODD) are calcific deposits that form in the optic nerve head secondary to abnormalities in axonal metabolism and degeneration. Anterior ischemic optic neuropathy, central retinal artery, and vein occlusion are among the rare vascular complications of disc drusen. We reported the clinical course of a 51-year-old patient with a unilateral acute nonarteritic anterior ischemic optic neuropathy (NAION) who received the diagnosis of bilateral optic disc drusen five years earlier ...

  2. Peripheral Neuropathy and Agent Orange

    ... Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset peripheral neuropathy is related to their exposure to Agent Orange or other herbicides during service when the disease ...

  3. Determinants of axonal regeneration

    Frisén, J

    1997-01-01

    Axons often regrow to their targets and lost functions may be restored after an injury in the peripheral nervous system. In contrast, axonal regeneration is generally very limited after injuries in the central nervous system, and functional impairment is usually permanent. The regenerative capacity depends on intrinsic neuronal factors as weil as the interaction of neurons with other cells. Glial cells may, in different situations, either support or inhibit axo...

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

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

    2012-08-01

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

  5. Megaoesophagus due to acrylamide neuropathy.

    Satchell, P M; McLeod, J G

    1981-01-01

    Greyhound dogs exposed to oral acrylamide for a period of eight weeks developed a sensorimotor peripheral neuropathy that had many features in common with acrylamide neuropathy seen in other species. Most of the animals also developed the clinical and radiological features of megaoesophagus. The association of neuropathy and megaoesophagus suggests that an axonopathy of the vagus may be an aetiological factor in this disorder.

  6. Peripheral Glia Have a Pivotal Role in the Initial Response to Axon Degeneration of Peripheral Sensory Neurons in Zebrafish

    Holly M Pope; Voigt, Mark M.

    2014-01-01

    Axon degeneration is a feature of many peripheral neuropathies. Understanding the organismal response to this degeneration may aid in identifying new therapeutic targets for treatment. Using a transgenic zebrafish line expressing a bacterial nitroreductase (Ntr)/mCherry fusion protein in the peripheral sensory neurons of the V, VII, IX, and X cranial nerves, we were able to induce and visualize the pathology of axon degeneration in vivo. Exposure of 4 days post fertilization Ntr larvae to the...

  7. HANSENS DISEASE : STUDY OF CLINICAL, NEUROPATHOLOGICAL, NEUROPHYSIOLOGICAL PATTERN OF LEPROUS NEUROPATHY

    Vijay Kumar

    2015-07-01

    Full Text Available A need still exists to determine the clinical and neurophysiological characteristics of leprosy neuropathy at distinct times of the disease by different methods that measure the various nerve fiber functions. A prospective clinical study was performed 100 patients of clinically proven Hansen’s will take in study and given diagnosis is made by dermatologist and neurologist. For Study of Clinical, Neuropathological , Neurophysiological Pattern of leprous neuropathy and results shows that Peripheral neuropath y is common neurological disorder, although population based studies are scarce. It is a diverse group of disorder with varying etiologies. Many of these are amenable to treatment while others are not. It affects all age groups are different etiologies in various age groups. Disorder is more common in males. Leprosy is still most common cause of peripheral neuropathy in this part of world. GBS is commonest cause in acutely presenting patients of peripheral neuropathy. Vacuities is also common especially in undiagnosed peripheral neuropathy patients and revealed by nerve biopsy. Tingling and numbness are two most common sensory complains. On objective sensory examination impairment of pain/temperature was most common. Evidence of large fiber dysfunction was less common. Almost half of leprous neuropathy had impaired joint position and vibration. Anesthetic patches and thickened nerve are two commonest indicators of leprous neuropathy. Among DTRs ankle jerk was most commonly affected. Almost half of GBS patie nts had history of preceding illness. Overall sensorimotor polyneuropathy was most common type of pattern after clinical - electrophysiological evaluation. Multiple mononeuropathy was most common in leprous neuropathy. Most patients had axonal type of invo lvement. In GBS patients predominantly motor neuropathy was found Skin smear examination is readily available and easy test to diagnosed leprosy, if done carefully. Sural nerve biopsy

  8. Recurrence Quantification Analysis of F-Waves and the Evaluation of Neuropathies

    Morris A. Fisher

    2015-01-01

    Full Text Available Electrodiagnostic (EDX patterns of neuropathic dysfunction have been based on axonal/demyelinating criteria requiring prior assumptions. This has not produced classifications of desired sensitivity or specificity. Furthermore, standard nerve conduction studies have limited reproducibility. New methodologies in EDX seem important. Recurrent Quantification Analysis (RQA is a nonlinear method for examining patterns of recurrence. RQA might provide a unique method for the EDX evaluation of neuropathies. RQA was used to analyze F-wave recordings from the abductor hallucis muscle in 61 patients with neuropathies. Twenty-nine of these patients had diabetes as the sole cause of their neuropathies. In the other 32 patients, the etiologies of the neuropathies were diverse. Commonly used EDX variables were also recorded. RQA data could separate the 29 patients with diabetic neuropathies from the other 32 patients (P<0.009. Statistically significant differences in two EDX variables were also present: compound muscle action potential amplitudes (P<0.007 and F-wave persistence (P<0.001. RQA analysis of F-waves seemed able to distinguish diabetic neuropathies from the other neuropathies studied, and this separation was associated with specific physiological abnormalities. This study would therefore support the idea that RQA of F-waves can distinguish between types of neuropathic dysfunction based on EDX data alone without prior assumptions.

  9. Sensory and motor neuropathy in a Border Collie.

    Harkin, Kenneth R; Cash, Walter C; Shelton, G Diane

    2005-10-15

    A 5-month-old female Border Collie was evaluated because of progressive hind limb ataxia. The predominant clinical findings suggested a sensory neuropathy. Sensory nerve conduction velocity was absent in the tibial, common peroneal, and radial nerves and was decreased in the ulnar nerve; motor nerve conduction velocity was decreased in the tibial, common peroneal, and ulnar nerves. Histologic examination of nerve biopsy specimens revealed considerable nerve fiber depletion; some tissue sections had myelin ovoids, foamy macrophages, and axonal degeneration in remaining fibers. Marked depletion of most myelinated fibers within the peroneal nerve (a mixed sensory and motor nerve) supported the electrodiagnostic findings indicative of sensorimotor neuropathy. Progressive deterioration in motor function occurred over the following 19 months until the dog was euthanatized. A hereditary link was not established, but a littermate was similarly affected. The hereditary characteristic of this disease requires further investigation. PMID:16266014

  10. Diagnosis of acute neuropathies

    Crone, Clarissa; Krarup, Christian

    2007-01-01

    Acute and subacute polyneuropathies present diagnostic challenges since many require prompt initiation of treatment in order to limit axonal degeneration and since an exact and detailed diagnosis is a prerequisite for making the correct choice of treatment. It is for instance of utmost importance...... to recognize whether the underlying pathological changes are due to demyelination or to axonal degeneration and electrodiagnostic tests can thus in most cases contribute considerably to the securing of an exact diagnosis. The specific and characteristic electrophysiological findings in the different...

  11. Diagnosis of acute neuropathies

    Crone, Clarissa; Krarup, Christian

    2007-01-01

    to recognize whether the underlying pathological changes are due to demyelination or to axonal degeneration and electrodiagnostic tests can thus in most cases contribute considerably to the securing of an exact diagnosis. The specific and characteristic electrophysiological findings in the different...

  12. Activity-Dependent Excitability Changes Suggest Na[superscript +]/K[superscript +] Pump Dysfunction in Diabetic Neuropathy

    Krishnan, Arun V.; Lin, Cindy S.-Y.; Kiernan, Matthew C.

    2008-01-01

    The present study was undertaken to evaluate the role of Na[superscript +]/K[superscript +] pump dysfunction in the development of diabetic neuropathy (DN). Nerve excitability techniques, which provide information about membrane potential and axonal ion channel function, were undertaken in 15 patients with established DN and in 10 patients with…

  13. Diabetic Neuropathies: The Nerve Damage of Diabetes

    ... Organizations (PDF, 293 KB). Alternate Language URL Español Diabetic Neuropathies: The Nerve Damage of Diabetes Page Content ... treated? Points to Remember Clinical Trials What are diabetic neuropathies? Diabetic neuropathies are a family of nerve ...

  14. Painful peripheral neuropathy

    Sun, Bo; Xu-sheng HUANG

    2013-01-01

    Painful peripheral neuropathy (PPN) is characterized by neuropathic pain (NP), which is accompanied by dysfunction of motor, sensory and autonomic nervous system. It always involves small nerve fibers, including A δ and C fibers. PPN can be classified into two types according to etiology: hereditary and acquired. Pain of PPN can manifest as spontaneous pain and stimulus-evoked pain (allodynia, hyperalgesia and hyperpathia). The manifestation of typical cases is length-dependent, which firstly...

  15. Infectious optic neuropathy.

    Golnik, Karl C

    2002-03-01

    A wide variety of infectious agents are known to cause optic neuropathy. This article will consider the bacteria, spirochetes, fungi, and viruses that most commonly affect the optic nerve. Clinical presentation is variable, but some pathogens often produce a characteristic funduscopic pattern. Diagnosis is usually made on the basis of clinical suspicion and serologic testing. Polymerase chain reaction is also increasingly utilized. Most infectious agents can be effectively treated but visual recovery is highly variable. PMID:15513450

  16. Multifocal motor neuropathy

    Thy P Nguyen; Vinay Chaudhry

    2011-01-01

    Multifocal motor neuropathy (MMN) is a unique disorder characterized by slowly progressive, asymmetric, distal and upper limb predominant weakness without significant sensory abnormalities. Electrophysiology is crucial to the diagnosis, revealing the hallmark partial conduction block. MMN is considered immune mediated due to the association with anti-GM1 antibodies and the response to immunomodulatory treatment. It is paramount to recognize MMN from other motor neuronopathies or peripheral ne...

  17. Catecholamines and diabetic autonomic neuropathy

    Hilsted, J

    1995-01-01

    plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors......In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity of...

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

    Carmen Cifuentes-Diaz

    Full Text Available 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

  19. Drug-induced peripheral neuropathy

    Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed;

    2014-01-01

    Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated with...

  20. Clinical and Electrophysiological Studies of a Family with Probable X-linked Dominant Charcot-Marie-Tooth Neuropathy and Ptosis.

    Tony Wu

    2004-07-01

    Full Text Available Background: The X-linked dominant Charcot-Marie-Tooth neuropathy (CMTX is ahereditary motor and sensory neuropathy linked to a variety of mutations inthe connexin32 (Cx32 gene. Clinical and genetic features of CMTX havenot previously been reported in Taiwanese.Methods: Clinical evaluations and electrophysiological studies were carried out on 25family members of a Taiwanese family group. Molecular genetic analysis ofthe Cx32 gene was performed. A sural nerve biopsy was obtained from 1patient.Results: Nine patients had clinical features of X-linked dominant inheritance and amoderate Charcot-Marie-Tooth (CMT neuropathy phenotype. Moleculargenetic analysis showed no mutation of the Cx32 coding region, but revealeda G-to-A transition at position -215 of the nerve-specific promoter P2 of theCx32 gene. Ptosis is 1 clinical manifestation of neuropathy in this probableCMTX family. Familial hyperthyroidism is an additional independent featureof the family. Electrophysiological and histological studies showed featuresof axonal neuropathy. Multimodality evoked potential studies revealed normalcentral motor and sensory conduction velocities.Conclusions: The presence of ptosis in this family illustrates the existence of clinical heterogeneityamong related family members with CMTX similar to that inCMT of autosomal inheritance. Electrophysiological and histological findingsrevealed normal central conduction and axonal neuropathy.

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

    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. Brain gangliosides in axon-myelin stability and axon regeneration

    Schnaar, Ronald L.

    2009-01-01

    Gangliosides, sialic acid-bearing glycosphingolipids, are expressed at high abundance and complexity in the brain. Altered ganglioside expression results in neural disorders, including seizures and axon degeneration. Brain gangliosides function, in part, by interacting with a ganglioside-binding lectin, myelin-associated glycoprotein (MAG). MAG, on the innermost wrap of the myelin sheath, binds to gangliosides GD1a and GT1b on axons. MAG-ganglioside binding ensures optimal axon-myelin cell-ce...

  3. Delayed radiation neuropathy

    A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author)

  4. Paclitaxel causes degeneration of both central and peripheral axon branches of dorsal root ganglia in mice

    Tasnim, Aniqa; Rammelkamp, Zoe; Slusher, Amy B.; Wozniak, Krystyna; Slusher, Barbara S.; Farah, Mohamed H.

    2016-01-01

    Background Peripheral neuropathy is a common and dose-limiting side effect of many cancer chemotherapies. The taxane agents, including paclitaxel (Taxol®), are effective chemotherapeutic drugs but cause degeneration of predominantly large myelinated afferent sensory fibers of the peripheral nervous system in humans and animal models. Dorsal root ganglia (DRG) neurons are sensory neurons that have unipolar axons each with two branches: peripheral and central. While taxane agents induce degener...

  5. Microfluidic control of axonal guidance

    Gu, Ling; Black, Bryan; Ordonez, Simon; Mondal, Argha; Jain, Ankur; Mohanty, Samarendra

    2014-10-01

    The precision of axonal pathfinding and the accurate formation of functional neural circuitry are crucial for an organism during development as well as during adult central and peripheral nerve regeneration. While chemical cues are believed to be primarily responsible for axonal pathfinding, we hypothesize that forces due to localized fluid flow may directly affect neuronal guidance during early organ development. Here, we report direct evidence of fluid flow influencing axonal migration, producing turning angles of up to 90°. Microfluidic flow simulations indicate that an axon may experience significant bending force due to cross-flow, which may contribute to the observed axonal turning. This method of flow-based guidance was successfully used to fasciculate one advancing axon onto another, showcasing the potential of this technique to be used for the formation of in vitro neuronal circuits.

  6. Diabetic autonomic neuropathy. The distribution of structural changes in sympathetic nerves of the BB rat.

    Yagihashi, S.; Sima, A A

    1985-01-01

    Ultrastructural and morphometric studies were performed longitudinally to characterize the topographic distribution of autonomic neuropathy in the BB-rat. Four levels of predominantly sympathetic nerves were examined. Typical axonal dystrophic changes were consistently increased in diabetic rats and were found to be most severe in the prevertebral celiac ganglion, the mesenteric nerve, the superior cervical ganglion, and the paravertebral ganglion, in that order. Dystrophic changes were also ...

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

    Quintyne, K I

    2011-01-01

    The authors herein report the case of a 35-year-old woman undergoing adjuvant therapy for node positive breast cancer, who presented with short and rapidly progressive history of bilateral lower limb symptoms of peripheral neuropathy following therapy with paclitaxel. MRI of her neural axis revealed no leptomeningeal enhancement or focal metastatic lesions. Neurophysiological tests favoured toxic sensory axonal polyneuropathy. She remains symptomatic following discontinuation of therapy 20 months ago, and is under review with pain management.

  8. Age-related intra-axonal accumulation of neurofilaments in the dorsal column nuclei of the cat brainstem: a light and electron microscopic immunohistochemical study.

    Zhang, J H; Sampogna, S; Morales, F R; Chase, M H

    1998-06-29

    In the present study, we examined the age-related intra-axonal accumulation of neurofilaments in the dorsal column nuclei of the cat by using immunohistochemical techniques combined with light and electron microscopy. Light microscopic analysis revealed oval or circular immunostained structures in the dorsal column nuclei of old cats. These immunostained structures were not observed in the material obtained from adult controls. Under the electron microscope, it was discovered that the immunostained structures were greatly enlarged axons with disrupted myelin sheaths. These enlarged axons contained massive accumulations of neurofilaments, some mitochondria, vacuoles and dense granules. The abnormalities of the myelin sheaths included the breaking of myelin at several locations, a splitting and ballooning in the myelin lamellae of the sheath and a distended periaxonal space between the axon and myelin sheaths. These ultrastructural changes resembled the degenerative alterations that have been observed in the axons of human and animals suffering from a number of pathological conditions, including giant axonal neuropathy and toxic neuropathy. Therefore, severely altered axons with intra-axonal accumulation of neurofilaments appear to reflect chronic degenerative changes that are a component of the aging process. PMID:9666164

  9. Clinical and neurophysiologic characterization of an European family with hereditary sensory neuropathy, paroxysmal cough and gastroesophageal reflux

    Pedro Barros

    2014-04-01

    Full Text Available In 2002, Spring et al reported a family with an autosomal dominant form of hereditary sensory neuropathy; patients also presented adult onset of gastroesophageal reflux and cough. Since then, no further families have been described. Objective: To study a new Portuguese family with these characteristics. Method: To describe the clinical and neurophysiologic characteristics of one family with features of sensory neuropathy associated with cough and gastroesophageal erflux. Results: Three of five siblings presented a similar history of paroxysmal cough (5th decade. About a decade later they experienced numbness and paraesthesia in the feets and in all cases there was evidence of an axonal sensory neuropathy. A history of gastroesophageal reflux of variable severity and age of onset was also present. Discussion: Molecular genetic studies have demonstrated genetic heterogeneity between the hereditary sensory neuropathy type 1 subtypes. The identification of these families is of major importance because further work is required to identify the underlying genetic defect.

  10. Warfarin improves neuropathy in monoclonal gammopathy of undetermined significance.

    Henry Gomez, Teny; Holkova, Beata; Noreika, Danielle; Del Fabbro, Egidio

    2016-01-01

    We report a case of a 60-year-old man who was referred to a palliative care clinic with monoclonal gammopathy of undetermined significance (MGUS)-associated neuropathy, responding to a therapeutic trial of warfarin. Electromyography showed distal symmetric sensory axonal neuropathy. The patient reported having had improvement of his neuropathic symptoms while taking warfarin postoperatively for thromboprophylaxis 1 year prior, and recurrence of his symptoms after the warfarin was discontinued. The patient was rechallenged with a trial of warfarin, targeting an international normalised ratio of 1.5-2.0. His pain scores decreased from 5/10 to 3/10 at 1 month and symptom improvement was maintained through 24 months of follow-up. Warfarin had a remarkable impact on our patient's symptoms and quality of life. The mechanisms mediating the symptomatic benefit with warfarin are unclear; however, a placebo effect is unlikely. Further studies may help guide the use of warfarin for MGUS-associated neuropathy. PMID:27317760

  11. Organophosphorus agent induced delayed neuropathy: a case report

    Harshit Acharya

    2016-02-01

    Full Text Available A 40-year old male, was presented with complaint of difficulty in walking with inability to flex foot and toes in bilateral feet ( and ldquo;foot drop and rdquo;, which was acute at the onset and gradually progressive since the past 7 days. The patient's wife and their 2 children had similar complaint with the same period of onset. At home, his family used cottonseed oil as cooking oil with wheat grain mixed with castor oil. On neurological examination, he was found to have lower motor neuron weakness with spasticity. After ruling out other common causes of polyneuropathy and lower motor weakness; due to high suspicion of poisoning by food adulterant, RBC acetyl cholinesterase (AChE and plasma cholinesterase (BuChE were tested at National Institute of Occupational Health (NIOH, which came low and confirmed diagnosis of Organophosphorus (OP poisoning. Nerve conduction study was done; which showed decreased amplitude of conduction in bilateral peroneal and right tibial nerve along with decreased mean nerve conduction velocity of bilateral median nerve. Thus patient was diagnosed with organophosphorus agent induced delayed axonal type of polyneuropathy and physiotherapy was started as treatment. OP compounds are a diverse group of chemicals which are principally used as insecticides in agriculture. Following organophosphate poisoning (OPP, 3 well-defined neurological syndromes are recognised: cholinergic crisis, intermediate syndrome and delayed polyneuropathy. Some organophosphates, particularly triorthocresyl phosphate (TOCP and tricresyl phosphate (TCP, produce delayed neuropathy. On ingestion, they do not produce significant cholinergic crisis, but 7 to 20 days later it leads to a pure motor axonal neuropathy with wrist and foot drop. The mechanism may involve inhibition of neuropathy target esterase (NTE, which is found in the brain, peripheral nerves, and lymphocytes. This form of toxicity has been seen occasionally in small epidemics in

  12. "Mitochondrial neuropathies": A survey from the large cohort of the Italian Network.

    Mancuso, Michelangelo; Orsucci, Daniele; Angelini, Corrado; Bertini, Enrico; Carelli, Valerio; Comi, Giacomo Pietro; Federico, Antonio; Minetti, Carlo; Moggio, Maurizio; Mongini, Tiziana; Tonin, Paola; Toscano, Antonio; Bruno, Claudio; Ienco, Elena Caldarazzo; Filosto, Massimiliano; Lamperti, Costanza; Diodato, Daria; Moroni, Isabella; Musumeci, Olimpia; Pegoraro, Elena; Spinazzi, Marco; Ahmed, Naghia; Sciacco, Monica; Vercelli, Liliana; Ardissone, Anna; Zeviani, Massimo; Siciliano, Gabriele

    2016-01-01

    Involvement of the peripheral nervous system in mitochondrial disorders has been previously reported. However, the prevalence of peripheral neuropathy in mitochondrial disorders is still unclear. Based on the large database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", we reviewed the clinical data of 1200 patients, with special regard to peripheral neuropathy (mean age at onset 24.3 ± 20.1 years; age at last evaluation 39.8 ± 22.3 years; females 52.7%; childhood onset [before age 16 years] 43.1%). Peripheral neuropathy was present in 143/1156 patients (12.4%), being one of the ten most common signs and symptoms. POLG mutations cause a potentially painful, axonal/mixed, mainly sensory polyneuropathy; TYMP mutations lead to a demyelinating sensory-motor polyneuropathy; SURF1 mutations are associated with a demyelinating/mixed sensory-motor polyneuropathy. The only mtDNA mutation consistently associated with peripheral neuropathy (although less severely than in the above-considered nuclear genes) was the m.8993T > G (or the rarer T > C) changes, which lead to an axonal, mainly sensory polyneuropathy. In conclusion, peripheral neuropathy is one of the most common features of a mitochondrial disorder, and may negatively impact on the quality of life of these patients. Furthermore, the presence or absence of peripheral neuropathy, as well as its specific forms and the association with neuropathic pain (indicative of a POLG-associated disease) can guide the molecular analysis. PMID:27020842

  13. Vincristine-Induced Cranial Neuropathy

    TALEBIAN, Ahmad; Razeieh GOUDARZI; Mohammadzadeh, Mahdi; Mirzadeh, Azadeh Sadat

    2014-01-01

    How to Cite This Article: Talebian A, Goudarzi RM, Mohammadzadeh M , Mirzadeh AS. Vincristine-Induced Cranial Neuropathy. Iran J Child Neurol. 2014 Winter; 8(1):66-68. AbstractVincristine (VCR) is a vinca alkaloid that is used for treatment of many malignancies.The vinca alkaloids are neurotoxic, usually causing a peripheral neuropathy, but cranial neuropathies are rare as side effects. Described here is the case of a 2.5-year-old boy, a known case of Wilms’ tumor, treated by vincristine (0/0...

  14. Leber Hereditary Optic Neuropathy

    Kopishinskaya S.V.

    2014-06-01

    Full Text Available Leber optic neuropathy is mitochondrial neurodegenerative disease manifested by progressive visual deterioration due to optic nerve atrophy. It is most frequently manifested in young people aged from 18 to 30, male patients prevailing. The disease is characterized by maternal inheritance, and the inheritance of a feature discontinues in men. In 95% cases Leber hereditary optic neuropathology is due to one of three known mitochondrial DNA mutations, its type being important in relation to the disease prognosis. The disease course has a number of succeeding stages: preclinical, acute and chronic (atrophic. The disease diagnosis is based on the characteristic clinical presentation of sequential impairment of both eyes forming central scotoma, the analysis of family history and detection of specific mutations. The present clinical observation illustrates the difficulties in Leber disease diagnosis.

  15. DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease.

    Hong, Young Bin; Kang, Junghee; Kim, Ji Hyun; Lee, Jinho; Kwak, Geon; Hyun, Young Se; Nam, Soo Hyun; Hong, Hyun Dae; Choi, Yu-Ri; Jung, Sung-Chul; Koo, Heasoo; Lee, Ji Eun; Choi, Byung-Ok; Chung, Ki Wha

    2016-05-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies. PMID:26786738

  16. Treatment of chronic inflammatory neuropathies

    F. Eftimov

    2015-01-01

    This thesis focuses on the efficacy of existing and alternative treatments in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) and explores predictors of treatment response in patients with CIDP treated with corticosteroids. The efficacy of intra

  17. Peripheral neuropathy in Lyme borreliosis

    Kindstrand, Eva

    1999-01-01

    Tick-transmitted Lyme borreliosis (LB) is frequently associated with manifestations from the peripheral nervous system. One aim of the thesis was to describe the relationship between peripheral neuropathy and LB by prospective studies of a) LB in some defined neurological conditions with peripheral nerve engagement and b) peripheral neuropathy in the late dermatological LB manifestation acrodermatitis chronica atrophicans (ACA). A second aim was to evaluate the effect of ant...

  18. The genetics of axonal transport and axonal transport disorders.

    Jason E Duncan

    2006-09-01

    Full Text Available Neurons are specialized cells with a complex architecture that includes elaborate dendritic branches and a long, narrow axon that extends from the cell body to the synaptic terminal. The organized transport of essential biological materials throughout the neuron is required to support its growth, function, and viability. In this review, we focus on insights that have emerged from the genetic analysis of long-distance axonal transport between the cell body and the synaptic terminal. We also discuss recent genetic evidence that supports the hypothesis that disruptions in axonal transport may cause or dramatically contribute to neurodegenerative diseases.

  19. Peripheral glia have a pivotal role in the initial response to axon degeneration of peripheral sensory neurons in zebrafish.

    Pope, Holly M; Voigt, Mark M

    2014-01-01

    Axon degeneration is a feature of many peripheral neuropathies. Understanding the organismal response to this degeneration may aid in identifying new therapeutic targets for treatment. Using a transgenic zebrafish line expressing a bacterial nitroreductase (Ntr)/mCherry fusion protein in the peripheral sensory neurons of the V, VII, IX, and X cranial nerves, we were able to induce and visualize the pathology of axon degeneration in vivo. Exposure of 4 days post fertilization Ntr larvae to the prodrug metronidazole (Met), which Ntr metabolizes into cytotoxic metabolites, resulted in dose-dependent cell death and axon degeneration. This was limited to the Ntr-expressing sensory neurons, as neighboring glia and motor axons were unaffected. Cell death was rapid, becoming apparent 3-4 hours after Met treatment, and was followed by phagocytosis of soma and axon debris by cells within the nerves and ganglia beginning at 4-5 hours of exposure. Although neutrophils appear to be activated in response to the degenerating neurons, they did not accumulate at the sites of degeneration. In contrast, macrophages were found to be attracted to the sites of the degenerating axons, where they phagocytosed debris. We demonstrated that peripheral glia are critical for both the phagocytosis and inflammatory response to degenerating neurons: mutants that lack all peripheral glia (foxD3-/-; Ntr) exhibit a much reduced reaction to axonal degeneration, resulting in a dramatic decrease in the clearance of debris, and impaired macrophage recruitment. Overall, these results show that this zebrafish model of peripheral sensory axon degeneration exhibits many aspects common to peripheral neuropathies and that peripheral glia play an important role in the initial response to this process. PMID:25058656

  20. Peripheral glia have a pivotal role in the initial response to axon degeneration of peripheral sensory neurons in zebrafish.

    Holly M Pope

    Full Text Available Axon degeneration is a feature of many peripheral neuropathies. Understanding the organismal response to this degeneration may aid in identifying new therapeutic targets for treatment. Using a transgenic zebrafish line expressing a bacterial nitroreductase (Ntr/mCherry fusion protein in the peripheral sensory neurons of the V, VII, IX, and X cranial nerves, we were able to induce and visualize the pathology of axon degeneration in vivo. Exposure of 4 days post fertilization Ntr larvae to the prodrug metronidazole (Met, which Ntr metabolizes into cytotoxic metabolites, resulted in dose-dependent cell death and axon degeneration. This was limited to the Ntr-expressing sensory neurons, as neighboring glia and motor axons were unaffected. Cell death was rapid, becoming apparent 3-4 hours after Met treatment, and was followed by phagocytosis of soma and axon debris by cells within the nerves and ganglia beginning at 4-5 hours of exposure. Although neutrophils appear to be activated in response to the degenerating neurons, they did not accumulate at the sites of degeneration. In contrast, macrophages were found to be attracted to the sites of the degenerating axons, where they phagocytosed debris. We demonstrated that peripheral glia are critical for both the phagocytosis and inflammatory response to degenerating neurons: mutants that lack all peripheral glia (foxD3-/-; Ntr exhibit a much reduced reaction to axonal degeneration, resulting in a dramatic decrease in the clearance of debris, and impaired macrophage recruitment. Overall, these results show that this zebrafish model of peripheral sensory axon degeneration exhibits many aspects common to peripheral neuropathies and that peripheral glia play an important role in the initial response to this process.

  1. Ultrastructure of rat sciatic nerve at the streptozotocin-induced neuropathy conditions under administration of alpha-lipoic acid preparations

    Dronov S.M.

    2014-09-01

    Full Text Available Dronov S.M. Ultrastructure of rat sciatic nerve at the streptozotocin-induced neuropathy conditions under administration of alpha-lipoic acid preparations. ABSTRACT. Background. Diabetic polyneuropathy is one of the most common long-term complications of diabetes. Hyperglycemias caused by ischemia and peroxidation of lipids are the presumed cause of diabetic neuropathy. Appointment of alpha-lipoic acid can restore the function of peripheral nerves, preventing the development of autonomic and trophic disorders. Objective. To determine the extent of changes in the ultrastructure of the sciatic nerve in rats with streptozotocin-induced simulated peripheral neuropathy in experimental therapy with α-lipoic acid. Methods. The research was conducted on 22 white rats divided randomly in 3 groups: group 1 – intact animals; group 2 – rats with streptozotocin-induced neuropathy; group 3 – rats with streptozotocin neuropathy + alpha-lipoic acid. Diabetes mellitus was induced in rats by a single intraperitoneal injection of streptozotocin (50 mg/kg. Alpha-lipoic acid was administered intraperitoneally and intragastrically once per day during 40 days from the 56th day after streptozotocin injection. Transmission electron microscopy was performed on the 40th day of alpha-lipoic acid administration. Results. Administration of alpha-lipoic acid activates compensatory-adaptive processes in neuronal cells, reduces the severity of violations in the composition of myelinated nerve fibers, contributes to a distinct axonal spruting, causes the reduction of asymmetrically distributed electron density in the lamellar structure of myelin, indicating an increase in the insulation of axons of the sciatic nerve fibers of rats. Conclusion. Experimental studies confirm high neuroprotective potential of alpha-lipoic acid in streptozotocin-induced neuropathy. Citation: Dronov SM. [Ultrastructure of rat sciatic nerve at the streptozotocin-induced neuropathy conditions

  2. Axonal tubulin and axonal microtubules: biochemical evidence for cold stability

    1984-01-01

    Nerve extracts containing tubulin labeled by axonal transport were analyzed by electrophoresis and differential extraction. We found that a substantial fraction of the tubulin in the axons of the retinal ganglion cell of guinea pigs is not solubilized by conventional methods for preparation of microtubules from whole brain. In two-dimensional polyacrylamide gel electrophoresis this cold-insoluble tubulin was biochemically distinct from tubulin obtained from whole brain microtubules prepared b...

  3. Organophosphate-induced delayed neuropathy: case report Neuropatia tardia por organofosforado: relato de caso

    Luiz Felipe R Vasconcellos

    2002-12-01

    Full Text Available Organophosphate induced delayed neuropathy (OPIDN is an uncommon clinical condition. It occurs in association with the ingestion of great amounts of organophosphate after the stimulation of cholinergic receptor. The clinical picture is characterized by a distal paresis in lower limbs associated with sensitive symptoms. Electrodiagnostic studies show a motor axonal neuropathy. Involvement of the central nervous system may occur. We describe a 39 years-old female patient who developed hyperesthesia associated with lower limbs paresis, fourteen days after she had ingested a Dichlorvos-based insecticide. Electrophysiological study was characterized by an axonal polyneuropathy pattern. Pyramidal tract dysfunction was observed later in upper limbs. Considering that both peripheral and central nervous systems are involved we believe that the more appropriated term would be organophosphate induced delayed neuropathy (OPIDN instead of organophosphate induced delayed polyneuropathy (OPIDP.A neuropatia tardia dos organofosforados (NTOF é condição clinica incomum. Geralmente ocorre após a intoxicação aguda por organofosforados, seguindo-se a fase de hiperestimulação colinérgica. O quadro clínico é caracterizado por déficit motor distal nos membros inferiores associado a sintomas sensitivos. O estudo eletroneuromiográfico tem demonstrado padrão axonal motor na maioria dos casos. Podem ocorrer sinais de comprometimento do sistema nervoso central. Descrevemos o caso de uma paciente de 39 anos que ingeriu inseticida a base de Dichlorvos e quatorze dias após apresentou quadro de hiperestesia associado a paresia distal nos membros inferiores. Realizou eletroneuromiografia que se caracterizou por padrão compatível com polineuropatia axonal. Sinais piramidais, de aparecimento mais tardio, foram observados nos membros superiores. Diante do comprometimento do sistema nervoso periférico e central, também consideramos o termo neuropatia tardia por

  4. Novel systems for in vivo monitoring and microenvironmental investigations of diabetic neuropathy in a murine model.

    Amit, Sharon; Yaron, Avraham

    2012-11-01

    Peripheral neuropathy is a devastating complication of diabetes conferring vast morbidity and mortality. Despite prolonged efforts to elucidate the mechanisms underlying diabetic related neuropathic phenomena and develop effective therapies, current treatment is for the most part glycemic control and symptomatic care. This is partially due to the intricate pathophysiology of diabetic neuropathy and the scarcity of valid experimental models. The aim of the study was to establish novel systems enabling monitoring and dissection of significant processes in the development of diabetic neuropathy. In a non-invasive in vivo model, two-photon microscopy is applied to evaluate mechanoreceptors (Meissner corpuscles) within an intact footpad of transgenic mice expressing a fluorescent neuronal tracer. By applying this advanced technology, which couples potent tissue penetration with superb resolution, we documented qualitative and quantitative diabetes-specific alterations in these sensory structures. Detection of such changes previously required laborious invasive histopathological techniques. In parallel, we present an ex vivo system that mimics the native microenvironment of the nerve ending via a unique co-culture of primary sensory neurons and thin skin slices. In conjunction with innovative high-throughput digital axonal measurements and computerized quantification tools, this method enables an unbiased exploration of neuronal autonomous and non-autonomous malfunctions. Using this setup we demonstrate that while the diabetic nerve retains a near-normal growth and regeneration capacities, the diabetic skin exhibits a decreased ability to support axonal outgrowth. Thus, an early target organ failure rather than intrinsic neuronal failure may initiate the neuropathy. Overall, the illustrated experimental platforms may greatly facilitate the holistic investigation of diabetic neuropathy. PMID:22592935

  5. Neurofilament Polymer Transport in Axons

    Yan, Yanping; Brown, Anthony

    2005-01-01

    Neurofilament proteins are known to be transported along axons by slow axonal transport, but the form in which they move is controversial. In previous studies on cultured rat sympathetic neurons, we found that green fluorescent protein-tagged neurofilament proteins move predominantly in the form of filamentous structures, and we proposed that these structures are single neurofilament polymers. In the present study, we have tested this hypothesis by using a rapid perfusion technique to capture...

  6. Local translation and directional steering in axons

    Lin, Andrew C; Holt, Christine E.

    2007-01-01

    The assembly of functional neural circuits in the developing brain requires neurons to extend axons to the correct targets. This in turn requires the navigating tips of axons to respond appropriately to guidance cues present along the axonal pathway, despite being cellular ‘outposts' far from the soma. Work over the past few years has demonstrated a critical role for local translation within the axon in this process in vitro, making axon guidance another process that requires spatially locali...

  7. An update on electrophysiological studies in neuropathy

    Krarup, Christian

    2003-01-01

    The review concentrates on the use of clinical neurophysiology in peripheral nerve disorders covered in the present issue. It is pertinent to distinguish different types of involvement of fibers in diabetic neuropathy, including the involvement of small and large fibers, to outline the diagnostic...... criteria of inflammatory neuropathies, and to describe the spectrum of peripheral nerve pathophysiology in inherited neuropathies. Painful neuropathies represent a particular challenge to clinical neurophysiology since it is mainly small fibers, which are difficult to study, that are affected....

  8. Phenotyping animal models of diabetic neuropathy

    Biessels, G J; Bril, V; Calcutt, N A;

    2014-01-01

    NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The...

  9. Diagnostic imaging of compression neuropathy

    Compression-induced neuropathy of peripheral nerves can cause severe pain of the foot and ankle. Early diagnosis is important to institute prompt treatment and to minimize potential injury. Although clinical examination combined with electrophysiological studies remain the cornerstone of the diagnostic work-up, in certain cases, imaging may provide key information with regard to the exact anatomic location of the lesion or aid in narrowing the differential diagnosis. In other patients with peripheral neuropathies of the foot and ankle, imaging may establish the etiology of the condition and provide information crucial for management and/or surgical planning. MR imaging and ultrasound provide direct visualization of the nerve and surrounding abnormalities. Bony abnormalities contributing to nerve compression are best assessed by radiographs and CT. Knowledge of the anatomy, the etiology, typical clinical findings, and imaging features of peripheral neuropathies affecting the peripheral nerves of the foot and ankle will allow for a more confident diagnosis. (orig.)

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

    Lei Wang

    2015-01-01

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

  11. Short-term peripheral nerve stimulation ameliorates axonal dysfunction after spinal cord injury.

    Lee, Michael; Kiernan, Matthew C; Macefield, Vaughan G; Lee, Bonne B; Lin, Cindy S-Y

    2015-05-01

    There is accumulating evidence that peripheral motor axons deteriorate following spinal cord injury (SCI). Secondary axonal dysfunction can exacerbate muscle atrophy, contribute to peripheral neuropathies and neuropathic pain, and lead to further functional impairment. In an attempt to ameliorate the adverse downstream effects that developed following SCI, we investigated the effects of a short-term peripheral nerve stimulation (PNS) program on motor axonal excitability in 22 SCI patients. Axonal excitability studies were undertaken in the median and common peroneal nerves (CPN) bilaterally before and after a 6-wk unilateral PNS program. PNS was delivered percutaneously over the median nerve at the wrist and CPN around the fibular head, and the compound muscle action potential (CMAP) from the abductor pollicis brevis and tibialis anterior was recorded. Stimulus intensity was above motor threshold, and pulses (450 μs) were delivered at 100 Hz with a 2-s on/off cycle for 30 min 5 days/wk. SCI patients had consistently high thresholds with a reduced CMAP consistent with axonal loss; in some patients the peripheral nerves were completely inexcitable. Nerve excitability studies revealed profound changes in membrane potential, with a "fanned-in" appearance in threshold electrotonus, consistent with membrane depolarization, and significantly reduced superexcitability during the recovery cycle. These membrane dysfunctions were ameliorated after 6 wk of PNS, which produced a significant hyperpolarizing effect. The contralateral, nonstimulated nerves remained depolarized. Short-term PNS reversed axonal dysfunction following SCI, may provide an opportunity to prevent chronic changes in axonal and muscular function, and may improve rehabilitation outcomes. PMID:25787956

  12. DNA testing in hereditary neuropathies.

    Murphy, Sinéad 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.

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

    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

  14. Axon density and axon orientation dispersion in children born preterm

    Kelly, Claire E.; Thompson, Deanne K.; Chen, Jian; Leemans, Alexander; Adamson, Christopher L.; Inder, Terrie E.; Cheong, Jeanie L Y; Doyle, Lex W.; Anderson, Peter J.

    2016-01-01

    Background Very preterm birth (VPT, <32 weeks' gestation) is associated with altered white matter fractional anisotropy (FA), the biological basis of which is uncertain but may relate to changes in axon density and/or dispersion, which can be measured using Neurite Orientation Dispersion and Density

  15. Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome: a slowly progressive disorder with stereotypical presentation.

    Cazzato, Daniele; Bella, Eleonora Dalla; Dacci, Patrizia; Mariotti, Caterina; Lauria, Giuseppe

    2016-02-01

    Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a newly described condition with onset in adulthood, characterized by progressive balance impairment and sensory disturbances in the lower limbs, which can severely affect patients' quality of life. Its pathogenesis remains obscure and the diagnosis challenging. We described four patients complaining of slowly progressive gait unbalance and sensory disturbances at the feet followed, after a period ranging 2-6 years, by cerebellar dysfunction. All patients showed gait and limb ataxia, positive Romberg sign, cerebellar dysarthria, gaze-evoked nystagmus, absent deep tendon reflexes, and impaired vibratory sensation. Nerve conduction studies revealed axonal sensory neuropathy, brain magnetic resonance imaging showed cerebellar atrophy, and otoneurological investigation demonstrated bilateral vestibular areflexia with impaired vestibulo-ocular reflexes. The diagnosis of CANVAS should be suspected on clinical ground based on homogeneous course of symptoms and signs, and addressed by video-oculography eye movement recording. PMID:26566912

  16. Outsourcing CREB translation to axons to survive

    Lin, Andrew C; Holt, Christine E.

    2008-01-01

    Nerve growth factor induces sensory neuron survival via retrograde signalling from the axon to the cell body. Local translation of the transcription factor CREB in the axon, followed by its transport to the nucleus, is involved in this process.

  17. Evaluation and Prevention of Diabetic Neuropathy

    Pajouhi M

    2007-07-01

    Full Text Available Background: Diabetic neuropathy is an incapacitating disease that afflicts almost 50 percent of patients with diabetes. A late finding in type 1 diabetes, diabetic neuropathy can be an early finding in non insulin-dependent diabetes. Diabetic neuropathies are divided primarily into two groups, sensorimotor and autonomic. Patients may acquire only one type of diabetic neuropathy or may present with combinations of neuropathies, such as autonomic neuropathy or distal symmetric polyneuropathy, the latter of which the most common form. Motor deficits, orthostatic hypotension, silent cardiac ischemia, hyperhidrosis, vasomotor instability, gastroparesis, bladder dysfunction, and sexual dysfunction can also result from diabetic neuropathy. Strict control of blood sugar, combined with proper daily foot care, is essential to avoid the complications of this disorder. With the potential to afflict any part of the nervous system, diabetic neuropathy should be suspected in all patients with type 2 diabetes as well as patients who have had type 1 diabetes for over five years. Although some patients with diabetic neuropathy notice few symptoms, upon physical examination mild to moderately severe sensory loss may be noted by the physician. Idiopathic neuropathy has been known to precede the onset of type 2 diabetes.

  18. Oxaliplatin-induced hyperexcitation of rat sciatic nerve fibers: an intra-axonal study.

    Kagiava, Alexia; Kosmidis, Efstratios K; Theophilidis, George

    2013-02-01

    Oxaliplatin is an agent that is used extensively in gastrointestinal cancer chemotherapy. The agent's major dose-limiting toxicity is peripheral neuropathy that can manifest as a chronic or an acute syndrome. Oxaliplatin-induced acute neuropathy is purportedly caused by an alteration of the biophysical properties of voltage-gated sodium channels. However, sodium channel blockers have not been successful at preventing acute neuropathy in the clinical setting. We report intra-axonal recordings from the isolated rat sciatic nerve preparation under the effect of oxaliplatin. The depolarization phase of single action potentials remains intact with a duration of 0.52 ± 0.02 ms (n=68) before and 0.55 ± 0.01 ms (n=68) after 1-5 h of exposure to 150 μM oxaliplatin (unpaired t-test, P > 0.05) whereas there is a significant broadening of the repolarization phase (2.16 ± 0.10 ms, n=68, before and 5.90 ± 0.32 ms after, n=68, unpaired t-test, P < 0.05). Apart from changes in spike shape, oxaliplatin also had drastic concentration- and time-dependent effects on the firing responses of fibers to short stimuli. In the intra-axonal recordings, three groups of firing patterns were indentified. The first group shows bursting (internal frequency 90 - 130 Hz, n=88), the second shows a characteristic plateau (at -19.27�2.84 mV, n=31, with durations ranging from 45 - 140 ms depending on the exposure time), and the third combines a plateau and a bursting period. Our results implicate the voltage-gated potassium channels as additional oxaliplatin targets, opening up new perspectives for the pharmacological prevention of peripheral neuropathy. PMID:22721389

  19. Axon damage and repair in multiple sclerosis.

    Perry, V.H.; Anthony, D. C.

    1999-01-01

    It is well known that within long-standing multiple sclerosis (MS) lesions there is axonal loss but whether it is an early or late event has been more difficult to establish. The use of immunocytochemical methods that reveal axonal end-bulbs is a valuable approach to investigating acute axonal injury in human pathological material. The application of these techniques to multiple sclerosis tissue reveals evidence of axonal injury in acute lesions; the distribution of the end-bulbs in acute and...

  20. Rationale, Science, and Economics of Surgical Nerve Decompression for Diabetic Neuropathy Foot Complications.

    Nickerson, David Scott

    2016-04-01

    Nerve decompression is effective and safe for dealing with the pain and numbness symptoms of the frequent nerve compression entrapments in diabetic symmetric peripheral neuropathy (DSPN). Evidence has accumulated of balance and stability improvements and protection against diabetic foot ulceration, recurrence and its complication cascade. Nerve decompression proffers significant benefit versus the large socioeconomic costs of DSPN complications. Advancing understanding of the mechanism of nerve compression and altered axonal activity in diabetes clarifies the basis of clinical benefit. Clinicians should seek out and recognize nerve entrapments and consider advising nerve decompression for relief of DSPN symptoms and prevention of complications. PMID:27013417

  1. Lifestyle risk factors for ulnar neuropathy and ulnar neuropathy-like symptoms

    Frost, Poul; Johnsen, Birger; Fuglsang-Frederiksen, Anders; Svendsen, Susanne Wulff

    2013-01-01

    Introduction: We examined whether lifestyle factors differ between patients with ulnar neuropathy confirmed by electroneurography (ENG) and those with ulnar neuropathy-like symptoms with normal ulnar nerve ENG. Methods: Among patients examined by ENG for suspected ulnar neuropathy, we identified...... 546 patients with ulnar neuropathy and 633 patients with ulnar neuropathy-like symptoms. These groups were compared with 2 separate groups of matched community referents and to each other. Questionnaire information on lifestyle was obtained. The electrophysiological severity of neuropathy was also...... graded. We used conditional and unconditional logistic regression. Results: Responses were obtained from 59%. Ulnar neuropathy was related to smoking, adjusted odds ratio (OR) 4.31 (95% confidence interval [CI] 2.43–7.64) for >24 pack-years. Ulnar neuropathy-like symptoms were related to body mass index...

  2. Axonal transport of enzymes and labeled proteins in experimental axonopathy induced by p-bromophenylacetylurea

    Axonal transport was studied by several techniques in the sciatic nerves of adult male Sprague-Dawley rats with neuropathy induced by treatment with p-bromophenylacetylurea (BPAU) in dimethylsulfoxide solution. Control rats were treated with solvent alone. BPAU, 200 mg/kg, induced severe muscle weakness in the hindlimbs, beginning after a latent period of 1 week and progressing to near total paralysis by 2 weeks. Axonal transport of the endogenous transmitter enzymes, acetylcholinesterase, dopamine-β-hydroxylase and choline acetyltransferase, was normal at both 2 and 15 days after administration of BPAU, as judged by the accumulation of enzyme activity above and below a set of double ligatures on the sciatic nerve. The velocity of fast anterograde transport of [35S]methionine labeled protein was also unaffected by BPAU. However, 4 abnormalities of transport were detected in BPAU treated rats. These abnormalities are discussed. (Auth.)

  3. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

    2016-01-01

    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

  4. Cardiovascular autonomic neuropathy in diabetes

    Spallone, Vincenza; Ziegler, Dan; Freeman, Roy;

    2011-01-01

    Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control...... in the setting of diabetes after exclusion of other causes. The prevalence of confirmed CAN is around 20%, and increases up to 65% with age and diabetes duration. Established risk factors for CAN are glycaemic control in type 1 and a combination of hypertension, dyslipidemia, obesity and glycaemic control...... in type 2 diabetes. CAN is a risk marker of mortality and cardiovascular morbidity, and possibly a progression promoter of diabetic nephropathy. Criteria for CAN diagnosis and staging are: 1. one abnormal cardio-vagal test identifies possible or early CAN; 2. at least two abnormal cardio-vagal tests...

  5. Treatment of gastrointestinal autonomic neuropathy.

    Törnblom, Hans

    2016-03-01

    The symptoms caused by gastrointestinal autonomic neuropathy in diabetes mellitus is important to highlight since it affects a large proportion of people with diabetes, regardless of whether this is type 1 or type 2. Gastroparesis and general signs of bowel dysfunction, such as constipation, diarrhoea and abdominal pain are most often encountered and involve both pharmacological and non-pharmacological treatment options. This mini-review summarises a presentation given at the 'Diagnosis and treatment of autonomic diabetic neuropathy in the gut' symposium at the 2015 annual meeting of the EASD. It is accompanied by another mini-review on a topic from this symposium (by Azpiroz and Malagelada, DOI: 10.1007/s00125-015-3831-1 ) and a commentary by the Session Chair, Péter Kempler (DOI: 10.1007/s00125-015-3826-y ). PMID:26634570

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

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

  7. Genetics Home Reference: hereditary sensory neuropathy type IA

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

  8. Treatment of chronic inflammatory neuropathies

    Schaik, van, I.N.; Eftimov, F.

    2015-01-01

    This thesis focuses on the efficacy of existing and alternative treatments in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) and explores predictors of treatment response in patients with CIDP treated with corticosteroids. The efficacy of intravenous immunoglobulin (IVIg) in CIDP and MMN was confirmed in meta-analyses. In CIDP, IVIg efficacy was similar to the efficacy of plasma exchange, prednisolone and intravenous methylprednisolone. ...

  9. Animal Models of Autoimmune Neuropathy

    Soliven, Betty

    2014-01-01

    The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy h...

  10. Treatment of painful diabetic neuropathy

    Javed, Saad; Petropoulos, Ioannis N.; Alam, Uazman; Malik, Rayaz A.

    2015-01-01

    Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, tr...

  11. Cranial Neuropathy in Multiple Sclerosis

    Mine Hayriye Sorgun; Bilge Koçer; Funda Kaplan; Nesrin Yılmaz; Nezih Yücemen; Canan Yücesan

    2011-01-01

    OBJECTIVE: It has been reported that cranial neuropathy findings could be seen in the neurologic examination of multiple sclerosis (MS) patients, although brain magnetic resonance imaging (MRI) may not reveal any lesion responsible for the cranial nerve involvement. The aim of this study was to determine the frequency of brainstem and cranial nerve involvement, except for olfactory and optic nerves, during MS attacks, and to investigate the rate of an available explanation for the cranial neu...

  12. Dyslipidemia-Induced Neuropathy in Mice

    Vincent, Andrea M.; Hayes, John M.; McLean, Lisa L.; Vivekanandan-Giri, Anuradha; Pennathur, Subramaniam; Eva L Feldman

    2009-01-01

    OBJECTIVE Neuropathy is a frequent and severe complication of diabetes. Multiple metabolic defects in type 2 diabetic patients result in oxidative injury of dorsal root ganglia (DRG) neurons. Our previous work focused on hyperglycemia clearly demonstrates induction of mitochondrial oxidative stress and acute injury in DRG neurons; however, this mechanism is not the only factor that produces neuropathy in vivo. Dyslipidemia also correlates with the development of neuropathy, even in pre-diabet...

  13. Alpha-Lipoic Acid and Diabetic Neuropathy

    Vallianou, Natalia; Evangelopoulos, Angelos; Koutalas, Pavlos

    2009-01-01

    Diabetic neuropathy presents a major public health problem. It is defined by the symptoms and signs of peripheral nerve dysfunction in diabetic patients, in whom other causes of neuropathy have been excluded. Pathogenetic mechanisms that have been implicated in diabetic neuropathy are: a) increased flux through the polyol pathway, leading to accumulation of sorbitol, a reduction in myo-inositol, and an associated reduced Na+-K+-ATPase activity, and b) endoneurial microvascular damage and hypo...

  14. Uremic Neuropathy: Epiemiological Study in Hemodialysis Patients

    Ricci, Davide

    2012-01-01

    Background/Aims. Uremic Neuropathy (UN) highly limits the individual self-sufficiency causing near-continuous pain. An estimation of the actual UN prevalence among hemodialysis patients was the aim of the present work. Methods. We studied 225 prevalent dialysis patients from two Italian Centres. The Michigan Neuropathy Score Instrument (MNSI), already validated in diabetic neuropathy, was used for the diagnosis of UN. It consisted of a questionnaire (MNSI_Q) and a physical-clinical evaluat...

  15. Vincristine-Induced Cranial Neuropathy

    Ahmad TALEBIAN*

    2013-12-01

    Full Text Available How to Cite This Article: Talebian A, Goudarzi RM, Mohammadzadeh M , Mirzadeh AS. Vincristine-Induced Cranial Neuropathy. Iran J Child Neurol. 2014 Winter; 8(1:66-68. Abstract Vincristine (VCR is a vinca alkaloid that is used for treatment of many malignancies. The vinca alkaloids are neurotoxic, usually causing a peripheral neuropathy, but cranial neuropathies are rare as side effects. Described here is the case of a 2.5-year-old boy, a known case of Wilms’ tumor, treated by vincristine (0/067 mg/kg/day and dactinomycin (0/045 mg/kg/day after surgery. Three weeks after treatment, he presented with bilateral ptosis. Neurological examination revealed bilateral ptosis with normal pupillary reflex and eye movement. He received 3.015 mg cumulative dose of vincristine before development of ptosis. Treatment with pyridoxine (150 mg/m2 p.o. BID and pyridostigmine (3 mg/kg p.o. BID started as neuroprotective agents, and after 7 days the problem disappeared. The treatment continued for 6 weeks and there were no signs of ptosis or a recurrence in follow up 2 months later.

  16. Peripheral Nerve Diffusion Tensor Imaging: Assessment of Axon and Myelin Sheath Integrity.

    A Heckel

    Full Text Available To investigate the potential of diffusion tensor imaging (DTI parameters as in-vivo biomarkers of axon and myelin sheath integrity of the median nerve in the carpal tunnel as validated by correlation with electrophysiology.MRI examinations at 3T including DTI were conducted on wrists in 30 healthy subjects. After manual segmentation of the median nerve quantitative analysis of fractional anisotropy (FA as well as axial, radial and mean diffusivity (AD, RD, and MD was carried out. Pairwise Pearson correlations with electrophysiological parameters comprising sensory nerve action potential (SNAP and compound muscle action potential (CMAP as markers of axon integrity, and distal motor latency (dml and sensory nerve conduction velocity (sNCV as markers of myelin sheath integrity were computed. The significance criterion was set at P=0.05, Bonferroni corrected for multiple comparisons.DTI parameters showed a distinct proximal-to-distal profile with FA, MD, and RD extrema coinciding in the center of the carpal tunnel. AD correlated with CMAP (r=0.50, p=0.04, Bonf. corr. but not with markers of myelin sheath integrity. RD correlated with sNCV (r=-0.53, p=0.02, Bonf. corr. but not with markers of axon integrity. FA correlated with dml (r=-0.63, p=0.002, Bonf. corr. and sNCV (r=0.68, p=0.001, Bonf. corr. but not with markers of axon integrity.AD reflects axon integrity, while RD (and FA reflect myelin sheath integrity as validated by correlation with electrophysiology. DTI parameters consistently indicate a slight decrease of structural integrity in the carpal tunnel as a physiological site of median nerve entrapment. DTI is particularly sensitive, since these findings are observed in healthy participants. Our results encourage future studies to evaluate the potential of DTI in differentiating axon from myelin sheath injury in patients with manifest peripheral neuropathies.

  17. Dimethyl Fumarate Ameliorates Lewis Rat Experimental Autoimmune Neuritis and Mediates Axonal Protection.

    Kalliopi Pitarokoili

    Full Text Available Dimethyl fumarate is an immunomodulatory and neuroprotective drug, approved recently for the treatment of relapsing-remitting multiple sclerosis. In view of the limited therapeutic options for human acute and chronic polyneuritis, we used the animal model of experimental autoimmune neuritis in the Lewis rat to study the effects of dimethyl fumarate on autoimmune inflammation and neuroprotection in the peripheral nervous system.Experimental autoimmune neuritis was induced by immunization with the neuritogenic peptide (amino acids 53-78 of P2 myelin protein. Preventive treatment with dimethyl fumarate given at 45 mg/kg twice daily by oral gavage significantly ameliorated clinical neuritis by reducing demyelination and axonal degeneration in the nerve conduction studies. Histology revealed a significantly lower degree of inflammatory infiltrates in the sciatic nerves. In addition, we detected a reduction of early signs of axonal degeneration through a reduction of amyloid precursor protein expressed in axons of the peripheral nerves. This reduction correlated with an increase of nuclear factor (erythroid derived 2-related factor 2 positive axons, supporting the neuroprotective potential of dimethyl fumarate. Furthermore, nuclear factor (erythroid derived 2-related factor 2 expression in Schwann cells was only rarely detected and there was no increase of Schwann cells death during EAN.We conclude that immunomodulatory and neuroprotective dimethyl fumarate may represent an innovative therapeutic option in human autoimmune neuropathies.

  18. Imaging of neuropathies about the hip

    Neuropathies about the hip may be cause of chronic pain and disability. In most cases, these conditions derive from mechanical or dynamic compression of a segment of a nerve within a narrow osteofibrous tunnel, an opening in a fibrous structure, or a passageway close to a ligament or a muscle. Although the evaluation of nerve disorders primarily relies on neurological examination and electrophysiology, diagnostic imaging is currently used as a complement to help define the site and aetiology of nerve compression and exclude other disease possibly underlying the patient’ symptoms. Diagnosis of entrapment neuropathies about the hip with US and MR imaging requires an in-depth knowledge of the normal imaging anatomy and awareness of the anatomic and pathologic factors that may predispose or cause a nerve injury. Accordingly, the aim of this article is to provide a comprehensive review of hip neuropathies with an emphasis on the relevant anatomy, aetiology, clinical presentation, and their imaging appearance. The lateral femoral cutaneous neuropathy (meiralgia paresthetica), femoral neuropathy, sciatic neuropathy, obturator neuropathy, superior and inferior gluteal neuropathies and pudendal neuropathy will be discussed

  19. Imaging of neuropathies about the hip

    Martinoli, Carlo, E-mail: carlo.martinoli@unige.it [Radiologia – DISC, Università di Genova, Largo Rosanna Benzi 8, I-16132 Genoa (Italy); Miguel-Perez, Maribel [Unit of Human Anatomy and Embryology, Department of Pathology and Experimental Therapy, Faculty of Medicine (C Bellvitge), University of Barcelona, Barcelona (Spain); Padua, Luca [Fondazione Don Gnocchi Onlus and Department of Neurology, Policlinico “A. Gemelli”, Università Cattolica del Sacro Cuore, Rome (Italy); Gandolfo, Nicola [IM2S – Institut Monégasque de Médecine and Chirurgie Sportive, Montecarlo (Monaco); Zicca, Anna [Radiologia – DISC, Università di Genova, Largo Rosanna Benzi 8, I-16132 Genoa (Italy); Tagliafico, Alberto [Radiologia – National Institute for Cancer Research, Genoa (Italy)

    2013-01-15

    Neuropathies about the hip may be cause of chronic pain and disability. In most cases, these conditions derive from mechanical or dynamic compression of a segment of a nerve within a narrow osteofibrous tunnel, an opening in a fibrous structure, or a passageway close to a ligament or a muscle. Although the evaluation of nerve disorders primarily relies on neurological examination and electrophysiology, diagnostic imaging is currently used as a complement to help define the site and aetiology of nerve compression and exclude other disease possibly underlying the patient’ symptoms. Diagnosis of entrapment neuropathies about the hip with US and MR imaging requires an in-depth knowledge of the normal imaging anatomy and awareness of the anatomic and pathologic factors that may predispose or cause a nerve injury. Accordingly, the aim of this article is to provide a comprehensive review of hip neuropathies with an emphasis on the relevant anatomy, aetiology, clinical presentation, and their imaging appearance. The lateral femoral cutaneous neuropathy (meiralgia paresthetica), femoral neuropathy, sciatic neuropathy, obturator neuropathy, superior and inferior gluteal neuropathies and pudendal neuropathy will be discussed.

  20. Human intraretinal myelination: Axon diameters and axon/myelin thickness ratios

    FitzGibbon, Thomas; Nestorovski, Zoran

    2013-01-01

    Purpose: Human intraretinal myelination of ganglion cell axons occurs in about 1% of the population. We examined myelin thickness and axon diameter in human retinal specimens containing myelinated retinal ganglion cell axons. Materials and Methods: Two eyes containing myelinated patches were prepared for electron microscopy. Two areas were examined in one retina and five in the second retina. Measurements were compared to normal retinal and optic nerve samples and the rabbit retina, which normally contains myelinated axons. Measurements were made using a graphics tablet. Results: Mean axon diameter of myelinated axons at all locations were significantly larger than unmyelinated axons (P ≤ 0.01). Myelinated axons within the patches were significantly larger than axons within the optic nerve (P < 0.01). The relationship between axon diameter/fiber diameter (the G-ratio) seen in the retinal sites differed from that in the nerve. G-ratios were higher and myelin thickness was positively correlated to axon diameter (P < 0.01) in the retina but negatively correlated to axon diameter in the nerve (P < 0.001). Conclusion: Intraretinally myelinated axons are larger than non-myelinated axons from the same population and suggests that glial cells can induce diameter changes in retinal axons that are not normally myelinated. This effect is more dramatic on intraretinal axons compared with the normal transition zone as axons enter the optic nerve and these changes are abnormal. Whether intraretinal myelin alters axonal conduction velocity or blocks axonal conduction remains to be clarified and these issues may have different clinical outcomes. PMID:24212308

  1. Immunotherapy Prospects for Painful Small-fiber Sensory Neuropathies and Ganglionopathies.

    Oaklander, Anne Louise

    2016-01-01

    The best-known peripheral neuropathies are those affecting the large, myelinated motor and sensory fibers. These have well-established immunological causes and therapies. Far less is known about the somatic and autonomic "small fibers"; the unmyelinated C-fibers, thinly myelinated A-deltas, and postganglionic sympathetics. The small fibers sense pain and itch, innervate internal organs and tissues, and modulate the inflammatory and immune responses. Symptoms of small-fiber neuropathy include chronic pain and itch, sensory impairment, edema, and skin color, temperature, and sweating changes. Small-fiber polyneuropathy (SFPN) also causes cardiovascular, gastrointestinal, and urological symptoms, the neurologic origin of which often remains unrecognized. Routine electrodiagnostic study does not detect SFPN, so skin biopsies immunolabeled to reveal axons are recommended for diagnostic confirmation. Preliminary evidence suggests that dysimmunity causes some cases of small-fiber neuropathy. Several autoimmune diseases, including Sjögren and celiac, are associated with painful small-fiber ganglionopathy and distal axonopathy, and some patients with "idiopathic" SFPN have evidence of organ-specific dysimmunity, including serological markers. Dysimmune SFPN first came into focus in children and teenagers as they lack other risk factors, for example diabetes or toxic exposures. In them, the rudimentary evidence suggests humoral rather than cellular mechanisms and complement consumption. Preliminary evidence supports efficacy of corticosteroids and immunoglobulins in carefully selected children and adult patients. This paper reviews the evidence of immune causality and the limited data regarding immunotherapy for small-fiber-predominant ganglionitis, regional neuropathy (complex regional pain syndrome), and distal SFPN. These demonstrate the need to develop case definitions and outcome metrics to improve diagnosis, enable prospective trials, and dissect the mechanisms of

  2. Isolation and analyses of axonal ribonucleoprotein complexes.

    Doron-Mandel, Ella; Alber, Stefanie; Oses, Juan A; Medzihradszky, Katalin F; Burlingame, Alma L; Fainzilber, Mike; Twiss, Jeffery L; Lee, Seung Joon

    2016-01-01

    Cytoskeleton-dependent RNA transport and local translation in axons are gaining increased attention as key processes in the maintenance and functioning of neurons. Specific axonal transcripts have been found to play roles in many aspects of axonal physiology including axon guidance, axon survival, axon to soma communication, injury response and regeneration. This axonal transcriptome requires long-range transport that is achieved by motor proteins carrying transcripts as messenger ribonucleoprotein (mRNP) complexes along microtubules. Other than transport, the mRNP complex plays a major role in the generation, maintenance, and regulation of the axonal transcriptome. Identification of axonal RNA-binding proteins (RBPs) and analyses of the dynamics of their mRNPs are of high interest to the field. Here, we describe methods for the study of interactions between RNA and proteins in axons. First, we describe a protocol for identifying binding proteins for an RNA of interest by using RNA affinity chromatography. Subsequently, we discuss immunoprecipitation (IP) methods allowing the dissection of protein-RNA and protein-protein interactions in mRNPs under various physiological conditions. PMID:26794529

  3. Penicillamin-induced neuropathy in rheumatoid arthritis

    Pedersen, P B; Hogenhaven, H

    1990-01-01

    A case of penicillamin-induced severe polyradiculopathy in rheumatoid arthritis is presented. The neuropathy was of demyelinating type, purely motor, proximal and clinically fully reversible when the drug ceased. In case of a progressive neuropathy, during penicillamin treatment, this adverse...

  4. SEVERE PERIPHERAL NEUROPATHY SECONDARY TO VINCRISTIN THERAPY

    Ayşe Oytun Bayrak

    2007-01-01

    Full Text Available Patients with hereditary neuropathy being at high risk of severe vincristin neurotoxicity are well known. Here, along with the review of the literature, we described two patients with unrecognized hereditary neuropathy who developed foot drop following low dose vincristin therapy. With this report we wanted to emphasize the importance of detailed neurologic examination and history taking before initiating therapy.

  5. Sensory neuropathy in two Border collie puppies.

    Vermeersch, K; Van Ham, L; Braund, K G; Bhatti, S; Tshamala, M; Chiers, K; Schrauwen, E

    2005-06-01

    A peripheral sensory neuropathy was diagnosed in two Border collie puppies. Neurological, electrophysiological and histopathological examinations suggested a purely sensory neuropathy with mainly distal involvement. Urinary incontinence was observed in one of the puppies and histological examination of the vagus nerve revealed degenerative changes. An inherited disorder was suspected. PMID:15971901

  6. MR imaging of trigeminal neuropathy

    Kim, Si Yeon; Yoon, Pyeong Ho; Chung, Jin Il; Lee, Seung Ik; Kim, Dong Ik [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    2001-03-01

    The trigeminal nerve is the largest of the cranial nerves and has both sensory and motor functions. It can be divided into proximal (brainstem, preganglionic, gasserian ganglion, and cavernous sinus) and distal (extracranial opthalmic, maxillary, and mandibular) segments. Patients with trigeminal neuropathy present with a wide variety of symptoms, and lesions producing those symptoms may occur anywhere along the protracted course of the trigeminal nerve, from its distal facial branches to its nuclear columns in the brainstem. The purpose of this article is to illustrate the normal anatomy of the trigeminal nerve and associated various pathologic conditions. These are arranged anatomically according to their site of interaction with it.

  7. MR imaging of trigeminal neuropathy

    The trigeminal nerve is the largest of the cranial nerves and has both sensory and motor functions. It can be divided into proximal (brainstem, preganglionic, gasserian ganglion, and cavernous sinus) and distal (extracranial opthalmic, maxillary, and mandibular) segments. Patients with trigeminal neuropathy present with a wide variety of symptoms, and lesions producing those symptoms may occur anywhere along the protracted course of the trigeminal nerve, from its distal facial branches to its nuclear columns in the brainstem. The purpose of this article is to illustrate the normal anatomy of the trigeminal nerve and associated various pathologic conditions. These are arranged anatomically according to their site of interaction with it

  8. Neuronal involvement in cisplatin neuropathy

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H;

    2007-01-01

    Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...... processes of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of...

  9. The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Hereditary Sensory Neuropathy.

    Suriyanarayanan, Saranya; Auranen, Mari; Toppila, Jussi; Paetau, Anders; Shcherbii, Maria; Palin, Eino; Wei, Yu; Lohioja, Tarja; Schlotter-Weigel, Beate; Schön, Ulrike; Abicht, Angela; Rautenstrauss, Bernd; Tyynismaa, Henna; Walter, Maggie C; Hornemann, Thorsten; Ylikallio, Emil

    2016-03-01

    Hereditary sensory and autonomic neuropathy 1 (HSAN1) is an autosomal dominant disorder that can be caused by variants in SPTLC1 or SPTLC2, encoding subunits of serine palmitoyl-CoA transferase. Disease variants alter the enzyme's substrate specificity and lead to accumulation of neurotoxic 1-deoxysphingolipids. We describe two families with autosomal dominant HSAN1C caused by a new variant in SPTLC2, c.547C>T, p.(Arg183Trp). The variant changed a conserved amino acid and was not found in public variant databases. All patients had a relatively mild progressive distal sensory impairment, with onset after age 50. Small fibers were affected early, leading to abnormalities on quantitative sensory testing. Sural biopsy revealed a severe chronic axonal neuropathy with subtotal loss of myelinated axons, relatively preserved number of non-myelinated fibers and no signs for regeneration. Skin biopsy with PGP9.5 labeling showed lack of intraepidermal nerve endings early in the disease. Motor manifestations developed later in the disease course, but there was no evidence of autonomic involvement. Patients had elevated serum 1-deoxysphingolipids, and the variant protein produced elevated amounts of 1-deoxysphingolipids in vitro, which proved the pathogenicity of the variant. Our results expand the genetic spectrum of HSAN1C and provide further detail about the clinical characteristics. Sequencing of SPTLC2 should be considered in all patients presenting with mild late-onset sensory-predominant small or large fiber neuropathy. PMID:26573920

  10. SETX mutations are a frequent genetic cause of juvenile and adult onset cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein

    Nanetti, Lorenzo; Cavalieri, Simona; Pensato, Viviana; Erbetta, Alessandra; Pareyson, Davide; Panzeri, Marta; Zorzi, Giovanna; Antozzi, Carlo; Moroni, Isabella; Gellera, Cinzia; Brusco, Alfredo; Mariotti, Caterina

    2013-01-01

    Objectives/background Ataxia with oculomotor apraxia defines a group of genetically distinct recessive ataxias including ataxia-telangectasia (A-T, ATM gene), ataxia with oculomotor apraxia type 1 (AOA1, APTX gene) and type 2 (AOA2, SETX gene). Although, a few unique clinical features differentiate each of these forms, the patients also share common clinical signs, such as the presence of cerebellar atrophy, sensorimotor axonal neuropathy, and elevated alpha-fetoprotein (AFP) serum level. Mat...

  11. The relationship of nerve fibre pathology to sensory function in entrapment neuropathy.

    Schmid, Annina B; Bland, Jeremy D P; Bhat, Manzoor A; Bennett, David L H

    2014-12-01

    Surprisingly little is known about the impact of entrapment neuropathy on target innervation and the relationship of nerve fibre pathology to sensory symptoms and signs. Carpal tunnel syndrome is the most common entrapment neuropathy; the aim of this study was to investigate its effect on the morphology of small unmyelinated as well as myelinated sensory axons and relate such changes to somatosensory function and clinical symptoms. Thirty patients with a clinical and electrophysiological diagnosis of carpal tunnel syndrome [17 females, mean age (standard deviation) 56.4 (15.3)] and 26 age and gender matched healthy volunteers [18 females, mean age (standard deviation) 51.0 (17.3)] participated in the study. Small and large fibre function was examined with quantitative sensory testing in the median nerve territory of the hand. Vibration and mechanical detection thresholds were significantly elevated in patients with carpal tunnel syndrome (P0.13). A skin biopsy was taken from a median nerve innervated area of the proximal phalanx of the index finger. Immunohistochemical staining for protein gene product 9.5 and myelin basic protein was used to evaluate morphological features of unmyelinated and myelinated axons. Evaluation of intraepidermal nerve fibre density showed a striking loss in patients (P0.07). However, patients displayed a significant increase in the percentage of elongated nodes (Pchannel distribution. Whereas neither neurophysiology nor quantitative sensory testing correlated with patients' symptoms or function deficits, the presence of elongated nodes was inversely correlated with a number of functional and symptom related scores (Pcarpal tunnel syndrome does not exclusively affect large fibres but is associated with loss of function in modalities mediated by both unmyelinated and myelinated sensory axons. We also document for the first time that entrapment neuropathies lead to a clear reduction in intraepidermal nerve fibre density, which was

  12. Sorting of Dendritic and Axonal Vesicles at the Pre-axonal Exclusion Zone

    Ginny G. Farías

    2015-11-01

    Full Text Available Polarized sorting of newly synthesized proteins to the somatodendritic and axonal domains of neurons occurs by selective incorporation into distinct populations of vesicular transport carriers. An unresolved issue is how the vesicles themselves are sorted to their corresponding neuronal domains. Previous studies concluded that the axon initial segment (AIS is an actin-based filter that selectively prevents passage of somatodendritic vesicles into the axon. We find, however, that most somatodendritic vesicles fail to enter the axon at a more proximal region in the axon hillock, herein referred to as the pre-axonal exclusion zone (PAEZ. Forced coupling of a somatodendritic cargo protein to an axonally directed kinesin is sufficient to drive transport of whole somatodendritic vesicles through the PAEZ toward the distal axon. Based on these findings, we propose that polarized sorting of transport vesicles occurs at the PAEZ and depends on the ability of the vesicles to acquire an appropriately directed microtubule motor.

  13. Coordinating gene expression and axon assembly to control axon growth: potential role of GSK3 signaling

    Fengquan Zhou

    2012-02-01

    Full Text Available Axon growth requires coordinated regulation of gene expression in the neuronal soma, anterograde transport of synthesized raw materials along the axon, and assembly of cytoskeleton and membranes in the nerve growth cone. Glycogen synthase kinase 3 (GSK3 signaling has recently been shown to play key roles in regulation of axonal transport and cytoskeletal assembly during axon growth. GSK3 signaling is also known to regulate gene expression via controlling the functions of many transcription factors, suggesting that GSK3 may be an important regulator of gene transcription supporting axon growth. Here we will review signaling pathways that control local axon assembly at the growth cone and gene expression in the soma during developmental or regenerative axon growth and discuss the potential involvement of GSK3 signaling in these processes, with a particular focus on how GSK3 signaling modulates the function of axon growth-associated transcription factors.

  14. Mitochondrial Transport and Docking in Axons

    Cai, Qian; Sheng, Zu-Hang

    2009-01-01

    Proper transport and distribution of mitochondria in axons and at synapses are critical for the normal physiology of neurons. Mitochondria in axons display distinct motility patterns and undergo saltatory and bidirectional movement, where mitochondria frequently stop, start moving again, and change direction. While approximately one-third of axonal mitochondria are mobile in mature neurons, a large proportion remains stationary. Their net movement is significantly influenced by recruitment to...

  15. Autonomic neuropathy in diabetes mellitus

    Alberto eVerrotti

    2014-12-01

    Full Text Available 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 (CAN 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.

  16. Vincristine-Induced Cranial Neuropathy

    Ahmad TALEBIAN*

    2014-01-01

    Full Text Available How to Cite This Article: Talebian A, Goudarzi RM, Mohammadzadeh M , Mirzadeh AS. Vincristine-Induced Cranial Neuropathy. Iran J Child Neurol. 2014 Winter; 8(1:66-68. AbstractVincristine (VCR is a vinca alkaloid that is used for treatment of many malignancies.The vinca alkaloids are neurotoxic, usually causing a peripheral neuropathy, but cranial neuropathies are rare as side effects. Described here is the case of a 2.5-year-old boy, a known case of Wilms’ tumor, treated by vincristine (0/067 mg/kg/day and dactinomycin (0/045 mg/kg/day after surgery. Three weeks after treatment, he presented with bilateral ptosis.Neurological examination revealed bilateral ptosis with normal pupillary reflex and eye movement. He received 3.015 mg cumulative dose of vincristine before development of ptosis.Treatment with pyridoxine (150 mg/m2 p.o. BID and pyridostigmine (3 mg/kg p.o. BID started as neuroprotective agents, and after 7 days the problem disappeared.The treatment continued for 6 weeks and there were no signs of ptosis or a recurrence in follow up 2 months later. References:Toopchizade V, Hosseini M, et al. Electrophysiological signs of neuropathy caused by vincristine. Medical Journal of Tabriz University of Medical Sciences. 2010 Autumn;31(3; 19-25.Gursel E.S. Vincristine-Induced Unilateral Ptosis in a Child. Pediatr Neurol 2009; 41:461-463.Ngamphaiboon N, Sweeney R, Wetzler M, Wang ES. Pyridoxine treatment of vincristine-induced cranial polyneuropathy in an adult patient with acute lymphocytic leukemia: Case report and review of the literature. Leuk Res. 2010 Aug;34(8:e194-6.Lash SC, Williams CP, Marsh CS, Crithchley C, Hodgkins PR, Mackie EJ. Acute Sixth-Nerve Palsy After Vincristine Therapy. Journal of AAPOS 2004 Feb;8(1: 67-8.Bay A, Yilmaz C, Yilmaz N, Oner AF. Vincristine induced cranial polyneuropathy. Indian J Pediatr. 2006 Jun;73(6:531-3.Tuxen M K, Hansen SW. Complication of treatment, Neurotoxicity secondary to antineoplastic

  17. The effect of Ginkgo extract EGb761 in cisplatin-induced peripheral neuropathy in mice

    Neuroprotective effect of Ginkgo biloba extract EGb761 in cisplatin (cis-diamminedi-chloroplatinum, or CDDP)-induced peripheral neuropathy was investigated. Swiss albino mice were treated with CDDP, 2 mg/kg ip twice a week for nine times. One group of the animals also received EGb761 in the drinking water at an estimated dosage of 100 mg/kg per day. Two other groups received vehicle (control) or EGb761 only. Development of neuropathy was evaluated with changes in sensory nerve conduction velocity (NCV). Following the treatments, dorsal root ganglia (DRGs) were microscopically examined and some were cultured for 3 days. EGb761 proved effective in preventing the reduction in NCV (P < 0.0001) caused by CDDP. CDDP caused a decrease in the number of migrating cells (P < 0.01) and in the length of outgrowing axons (P < 0.01) while EGb761 treatment prevented the latter. CDDP led to smaller nuclear and somatic sizes in neurons (P < 0.01), while with EGb761 co-administration, both were close to control values. Animals having EGb761 only had similar results with controls. In conclusion, EGb761 was found to be effective in preventing some functional and morphological deteriorations in CDDP-induced peripheral neuropathy

  18. AxonSeg: Open Source Software for Axon and Myelin Segmentation and Morphometric Analysis.

    Zaimi, Aldo; Duval, Tanguy; Gasecka, Alicja; Côté, Daniel; Stikov, Nikola; Cohen-Adad, Julien

    2016-01-01

    Segmenting axon and myelin from microscopic images is relevant for studying the peripheral and central nervous system and for validating new MRI techniques that aim at quantifying tissue microstructure. While several software packages have been proposed, their interface is sometimes limited and/or they are designed to work with a specific modality (e.g., scanning electron microscopy (SEM) only). Here we introduce AxonSeg, which allows to perform automatic axon and myelin segmentation on histology images, and to extract relevant morphometric information, such as axon diameter distribution, axon density and the myelin g-ratio. AxonSeg includes a simple and intuitive MATLAB-based graphical user interface (GUI) and can easily be adapted to a variety of imaging modalities. The main steps of AxonSeg consist of: (i) image pre-processing; (ii) pre-segmentation of axons over a cropped image and discriminant analysis (DA) to select the best parameters based on axon shape and intensity information; (iii) automatic axon and myelin segmentation over the full image; and (iv) atlas-based statistics to extract morphometric information. Segmentation results from standard optical microscopy (OM), SEM and coherent anti-Stokes Raman scattering (CARS) microscopy are presented, along with validation against manual segmentations. Being fully-automatic after a quick manual intervention on a cropped image, we believe AxonSeg will be useful to researchers interested in large throughput histology. AxonSeg is open source and freely available at: https://github.com/neuropoly/axonseg. PMID:27594833

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

    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.

  20. Axonal regeneration through arterial grafts.

    Anderson, P. N.; Turmaine, M.

    1986-01-01

    The left common peroneal nerves of adult inbred mice were severed and allowed to regenerate through the lumina of Y-shaped tubes comprising grafts of abdominal aorta and its bifurcation. Very little regeneration took place within the grafts unless the distal nerve stump was inserted into one limb of the Y-tube. Using syngeneic grafts virtually all the axons regenerating through the lumen grew down the limb of the Y-tube containing the distal nerve. Using non-syngeneic grafts, however, a subst...

  1. Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy

    Khadilkar Satish

    2011-01-01

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

  2. Comparison of electrophysiological findings in axonal and demyelinating Guillain-Barre syndrome.

    Samira Yadegari

    2014-09-01

    Full Text Available Incidence and predominant subtype of Guillain-Barre syndrome (GBS differs geographically. Electrophysiology has an important role in early diagnosis and prediction of prognosis. This study is conducted to determine the frequent subtype of GBS in a large group of patients in Iran and compare nerve conduction studies in axonal and demyelinating forms of GBS.We retrospectively evaluated the medical records and electrodiagnostic study (EDS of 121 GBS patients who were managed in our hospital during 11 years. After regarding the exclusion criteria, patients classified as three groups: acute inflammatory demyelinating polyneuropathy (AIDP, acute motor axonal neuropathy (AMAN, and acute motor sensory axonal neuropathy (AMSAN. The most frequent subtype and then electrophysiological characteristic based on the time of EDS and their cerebrospinal fluid (CSF profile were assessed.Among 70 patients finally included in the study, 67% were men. About 63%, 23%, and 14% had AIDP, AMAN, and AMSAN, respectively. AIDP patients represented a wider range of ages compared with other groups. Higher levels of CSF protein, abnormal late responses and sural sparing were more frequent in AIDP subtype. Five AMSAN patients also revealed sural sparing. Conduction block (CB was observed in one AMAN patient. Prolonged F-wave latency was observed only in AIDP cases. CB and inexcitable sensory nerves were more frequent after 2 weeks, but reduced F-wave persistency was more prominent in the early phase.AIDP was the most frequent subtype. Although the electrophysiology and CSF are important diagnostic tools, classification should not be made based on a distinct finding.

  3. Axonal interferon responses and alphaherpesvirus neuroinvasion

    Song, Ren

    Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at a peripheral epithelial surface and continues into the peripheral nervous system (PNS) that innervates this tissue. Inflammatory responses are induced at the infected peripheral site prior to viral invasion of the PNS. PNS neurons are highly polarized cells with long axonal processes that connect to distant targets. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which include type I interferon (e.g. IFNbeta) and type II interferon (i.e. IFNgamma). IFNbeta can be produced by all types of cells, while IFNgamma is secreted by some specific types of immune cells. And both types of IFN induce antiviral responses in surrounding cells that express the IFN receptors. The fundamental question is how do PNS neurons respond to the inflammatory milieu experienced only by their axons. Axons must act as potential front-line barriers to prevent PNS infection and damage. Using compartmented cultures that physically separate neuron axons from cell bodies, I found that pretreating isolated axons with IFNbeta or IFNgamma significantly diminished the number of HSV-1 and PRV particles moving from axons to the cell bodies in an IFN receptor-dependent manner. Furthermore, I found the responses in axons are activated differentially by the two types of IFNs. The response to IFNbeta is a rapid, axon-only response, while the response to IFNgamma involves long distance signaling to the PNS cell body. For example, exposing axons to IFNbeta induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFNgamma induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated IFNgamma-, but not IFNbeta-mediated antiviral effects. Proteomic analysis of IFNbeta- or IFNgamma-treated axons identified several differentially regulated proteins. Therefore

  4. Neurofilament spacing, phosphorylation, and axon diameter in regenerating and uninjured lamprey axons.

    Pijak, D S; Hall, G F; Tenicki, P J; Boulos, A S; Lurie, D I; Selzer, M E

    1996-05-13

    It has been postulated that phosphorylation of the carboxy terminus sidearms of neurofilaments (NFs) increases axon diameter through repulsive electrostatic forces that increase sidearm extension and interfilament spacing. To evaluate this hypothesis, the relationships among NF phosphorylation, NF spacing, and axon diameter were examined in uninjured and spinal cord-transected larval sea lampreys (Petromyzon marinus). In untransected animals, axon diameters in the spinal cord varied from 0.5 to 50 microns. Antibodies specific for highly phosphorylated NFs labeled only large axons (> 10 microns), whereas antibodies for lightly phosphorylated NFs labeled medium-sized and small axons more darkly than large axons. For most axons in untransected animals, diameter was inversely related to NF packing density, but the interfilament distances of the largest axons were only 1.5 times those of the smallest axons. In addition, the lightly phosphorylated NFs of the small axons in the dorsal columns were widely spaced, suggesting that phosphorylation of NFs does not rigidly determine their spacing and that NF spacing does not rigidly determine axon diameter. Regenerating neurites of giant reticulospinal axons (GRAs) have diameters only 5-10% of those of their parent axons. If axon caliber is controlled by NF phosphorylation via mutual electrostatic repulsion, then NFs in the slender regenerating neurites should be lightly phosphorylated and densely packed (similar to NFs in uninjured small caliber axons), whereas NFs in the parent GRAs should be highly phosphorylated and loosely packed. However, although linear density of NFs (the number of NFs per micrometer) in these slender regenerating neurites was twice that in their parent axons, they were highly phosphorylated. Following sectioning of these same axons close to the cell body, axon-like neurites regenerated ectopically from dendritic tips. These ectopically regenerating neurites had NF linear densities 2.5 times those of

  5. Axon reflexes in human cold exposed fingers

    Daanen, H.A.M.; Ducharme, M.B.

    2000-01-01

    Exposure of fingers to severe cold induces cold induced vasodilation (CIVD). The mechanism of CIVD is still debated. The original theory states that an axon reflex causes CIVD. To test this hypothesis, axon reflexes were evoked by electrical stimulation of the middle fingers of hands immersed in wat

  6. Cable energy function of cortical axons.

    Ju, Huiwen; Hines, Michael L; Yu, Yuguo

    2016-01-01

    Accurate estimation of action potential (AP)-related metabolic cost is essential for understanding energetic constraints on brain connections and signaling processes. Most previous energy estimates of the AP were obtained using the Na(+)-counting method, which seriously limits accurate assessment of metabolic cost of ionic currents that underlie AP conduction along the axon. Here, we first derive a full cable energy function for cortical axons based on classic Hodgkin-Huxley (HH) neuronal equations and then apply the cable energy function to precisely estimate the energy consumption of AP conduction along axons with different geometric shapes. Our analytical approach predicts an inhomogeneous distribution of metabolic cost along an axon with either uniformly or nonuniformly distributed ion channels. The results show that the Na(+)-counting method severely underestimates energy cost in the cable model by 20-70%. AP propagation along axons that differ in length may require over 15% more energy per unit of axon area than that required by a point model. However, actual energy cost can vary greatly depending on axonal branching complexity, ion channel density distributions, and AP conduction states. We also infer that the metabolic rate (i.e. energy consumption rate) of cortical axonal branches as a function of spatial volume exhibits a 3/4 power law relationship. PMID:27439954

  7. Cable energy function of cortical axons

    Ju, Huiwen; Hines, Michael L.; Yu, Yuguo

    2016-01-01

    Accurate estimation of action potential (AP)-related metabolic cost is essential for understanding energetic constraints on brain connections and signaling processes. Most previous energy estimates of the AP were obtained using the Na+-counting method, which seriously limits accurate assessment of metabolic cost of ionic currents that underlie AP conduction along the axon. Here, we first derive a full cable energy function for cortical axons based on classic Hodgkin-Huxley (HH) neuronal equations and then apply the cable energy function to precisely estimate the energy consumption of AP conduction along axons with different geometric shapes. Our analytical approach predicts an inhomogeneous distribution of metabolic cost along an axon with either uniformly or nonuniformly distributed ion channels. The results show that the Na+-counting method severely underestimates energy cost in the cable model by 20–70%. AP propagation along axons that differ in length may require over 15% more energy per unit of axon area than that required by a point model. However, actual energy cost can vary greatly depending on axonal branching complexity, ion channel density distributions, and AP conduction states. We also infer that the metabolic rate (i.e. energy consumption rate) of cortical axonal branches as a function of spatial volume exhibits a 3/4 power law relationship. PMID:27439954

  8. Neuronal Development: SAD Kinases Make Happy Axons

    Xing, Lei; Newbern, Jason M.; Snider, William D

    2013-01-01

    The polarity proteins LKB1 and SAD-A/B are key regulators of axon specification in the developing cerebral cortex. Recent studies now show that this mechanism cannot be generalized to other classes of neurons: instead, SAD-A/B functions downstream of neurotrophin signaling in sensory neurons to mediate a later stage of axon development — arborization in the target field.

  9. Muscular atrophy in diabetic neuropathy

    Andersen, H; Gadeberg, P C; Brock, B;

    1997-01-01

    Diabetic patients with polyneuropathy develop motor dysfunction. To establish whether motor dysfunction is associated with muscular atrophy the ankle dorsal and plantar flexors of the non-dominant leg were evaluated with magnetic resonance imaging in 8 patients with symptomatic neuropathy, in 8 non......-neuropathic patients and in 16 individually matched control subjects. In the neuropathic patients the muscle strength of the ankle dorsal and plantar flexors was reduced by 41 % as compared to the non-neuropathic patients (p < 0.005). Volume of the ankle dorsal and plantar flexors was estimated with stereological...... confirmed that the atrophy predominated distally. We conclude that muscular atrophy underlies motor weakness at the ankle in diabetic patients with polyneuropathy and that the atrophy is most pronounced in distal muscles of the lower leg indicating that a length dependent neuropathic process explains the...

  10. Linezolid-induced optic neuropathy

    Divya Karuppannasamy

    2014-01-01

    Full Text Available Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment.

  11. Dynamics of mitochondrial transport in axons

    Robert Francis Niescier

    2016-05-01

    Full Text Available The polarized structure and long neurites of neurons pose a unique challenge for proper mitochondrial distribution. It is widely accepted that mitochondria move from the cell body to axon ends and vice versa; however, we have found that mitochondria originating from the axon ends moving in the retrograde direction never reach to the cell body, and only a limited number of mitochondria moving in the anterograde direction from the cell body arrive at the axon ends of mouse hippocampal neurons. Furthermore, we have derived a mathematical formula using the Fokker-Planck equation to characterize features of mitochondrial transport, and the equation could determine altered mitochondrial transport in axons overexpressing parkin. Our analysis will provide new insights into the dynamics of mitochondrial transport in axons of normal and unhealthy neurons.

  12. Dynamics of Mitochondrial Transport in Axons.

    Niescier, Robert F; Kwak, Sang Kyu; Joo, Se Hun; Chang, Karen T; Min, Kyung-Tai

    2016-01-01

    The polarized structure and long neurites of neurons pose a unique challenge for proper mitochondrial distribution. It is widely accepted that mitochondria move from the cell body to axon ends and vice versa; however, we have found that mitochondria originating from the axon ends moving in the retrograde direction never reach to the cell body, and only a limited number of mitochondria moving in the anterograde direction from the cell body arrive at the axon ends of mouse hippocampal neurons. Furthermore, we have derived a mathematical formula using the Fokker-Planck equation to characterize features of mitochondrial transport, and the equation could determine altered mitochondrial transport in axons overexpressing parkin. Our analysis will provide new insights into the dynamics of mitochondrial transport in axons of normal and unhealthy neurons. PMID:27242435

  13. Early events in axon/dendrite polarization.

    Cheng, Pei-lin; Poo, Mu-ming

    2012-01-01

    Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure. PMID:22715881

  14. Infectious optic neuropathies: a clinical update

    Kahloun R

    2015-09-01

    Full Text Available Rim Kahloun, Nesrine Abroug, Imen Ksiaa, Anis Mahmoud, Hatem Zeghidi, Sonia Zaouali, Moncef KhairallahDepartment of Ophthalmology, Fattouma Bourguiba University Hospital, Faculty of Medicine, University of Monastir, Monastir, TunisiaAbstract: Different forms of optic neuropathy causing visual impairment of varying severity have been reported in association with a wide variety of infectious agents. Proper clinical diagnosis of any of these infectious conditions is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular findings. Diagnosis is confirmed by serologic testing and polymerase chain reaction in selected cases. Treatment of infectious optic neuropathies involves the use of specific anti-infectious drugs and corticosteroids to suppress the associated inflammatory reaction. The visual prognosis is generally good, but persistent severe vision loss with optic atrophy can occur. This review presents optic neuropathies caused by specific viral, bacterial, parasitic, and fungal diseases.Keywords: optic neuropathy, viruses, bacteria, parasites, fungi, vaccination

  15. Bicycling induced pudendal nerve pressure neuropathy.

    Silbert, P L; Dunne, J W; Edis, R H; Stewart-Wynne, E G

    1991-01-01

    Pudendal neuropathies are well recognised as part of more generalised peripheral neuropathies; however, focal abnormalities of the pudendal nerve due to cycling-related injuries have been infrequently reported. We describe two patients who developed pudendal neuropathies secondary to pressure effects on the perineum from racing-bicycle saddles. Both were male competitive athletes, one of whom developed recurrent numbness of the penis and scrotum after prolonged cycling; the other developed numbness of the penis, an altered sensation of ejaculation, with disturbance of micturition and reduced awareness of defecation. Both patients improved with alterations in saddle position and riding techniques. We conclude that pudendal nerve pressure neuropathy can result from prolonged cycling, particularly when using a poor riding technique. PMID:1821826

  16. Sildenafil ameliorates long term peripheral neuropathy in type II diabetic mice.

    Lei Wang

    Full Text Available Diabetic peripheral neuropathy is a common complication of long-standing diabetes mellitus. To mimic clinical trials in which patients with diabetes enrolled have advanced peripheral neuropathy, we investigated the effect of sildenafil, a specific inhibitor of phosphodiesterase type 5 enzyme, on long term peripheral neuropathy in middle aged male mice with type II diabetes. Treatment of diabetic mice (BKS.Cg-m+/+Leprdb/J, db/db at age 36 weeks with sildenafil significantly increased functional blood vessels and regional blood flow in the sciatic nerve, concurrently with augmentation of intra-epidermal nerve fiber density in the skin and myelinated axons in the sciatic nerve. Functional analysis showed that the sildenafil treatment considerably improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal stimulus sensitivity compared with the saline treatment. In vitro studies showed that mouse dermal endothelial cells (MDE cultured under high glucose levels exhibited significant down regulation of angiopoietin 1 (Ang1 expression and reduction of capillary-like tube formation, which were completely reversed by sildenafil. In addition, incubation of dorsal root ganglia (DRG neurons with conditioned medium harvested from MDE under high glucose levels suppressed neurite outgrowth, where as conditional medium harvested from MDE treated with sildenafil under high glucose levels did not inhibit neurite outgrowth of DRG neurons. Moreover, blockage of the Ang1 receptor, Tie2, with a neutralized antibody against Tie2 abolished the beneficial effect of sildenafil on tube formation and neurite outgrowth. Collectively, our data indicate that sildenafil has a therapeutic effect on long term peripheral neuropathy of middle aged diabetic mice and that improvement of neurovascular dysfunction by sildenafil likely contributes to the amelioration of nerve function. The Ang1/Tie2 signaling pathway may play an important role in these

  17. Multiple cranial neuropathies following etanercept administration.

    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

  18. Optimal myelin elongation relies on YAP activation by axonal growth and inhibition by Crb3/Hippo pathway.

    Fernando, Ruani N; Cotter, Laurent; Perrin-Tricaud, Claire; Berthelot, Jade; Bartolami, Sylvain; Pereira, Jorge A; Gonzalez, Sergio; Suter, Ueli; Tricaud, Nicolas

    2016-01-01

    Fast nerve conduction relies on successive myelin segments that electrically isolate axons. Segment geometry-diameter and length-is critical for the optimization of nerve conduction and the molecular mechanisms allowing this optimized geometry are partially known. We show here that peripheral myelin elongation is dynamically regulated by stimulation of YAP (Yes-associated protein) transcription cofactor activity during axonal elongation and limited by inhibition of YAP activity via the Hippo pathway. YAP promotes myelin and non-myelin genes transcription while the polarity protein Crb3, localized at the tips of the myelin sheath, activates the Hippo pathway to temper YAP activity, therefore allowing for optimal myelin growth. Dystrophic Dy(2j/2j) mice mimicking human peripheral neuropathy with reduced internodal lengths have decreased nuclear YAP which, when corrected, leads to longer internodes. These data show a novel mechanism controlling myelin growth and nerve conduction, and provide a molecular ground for disease with short myelin segments. PMID:27435623

  19. Detection of neuropathy using a sudomotor test in type 2 diabetes

    Gandhi PG

    2015-01-01

    Full Text Available Pratiksha G Gandhi,1 Gundu HR Rao21IPC Heart Centre, Mumbai, India; 2University of Minnesota, Minneapolis, MN, USABackground: The sudomotor test is used to evaluate the postganglionic cholinergic sympathetic nervous system. The aim of this study was to evaluate the efficacy of a sudomotor testing device to detect peripheral distal neuropathy (PDN and cardiac autonomic neuropathy (CAN in patients with type 2 diabetes.Materials and methods: A total of 133 type 2 diabetic patients were included in the study. The patients underwent examination at the IPC Heart Care Centre (Mumbai, India in order to assess the diabetic neuropathy symptoms (DNS score, using a questionnaire, and the CAN score, using heart rate variability analysis and Ewing tests. In addition, patients were given a sudomotor test using the SudoPath™ system. The diagnosis of PDN is based on the DNS score. A DNS score of 1 or higher is defined as a positive result for PDN. According to the DNS score, the patients were separated into two groups: Group 1 comprised 35 patients (21 males, with the mean age of 66 years (standard deviation [SD] =12.1, who had a DNS score ≥1. Group 2 comprised 98 patients (65 males, with the mean age of 56 years (SD =9.6, who had a DNS score =0. The SudoPath system is a galvanic skin response device that uses the quantitative sudomotor axon reflex approach to assess for small and unmyelinated fiber neuropathy. The system provides a sudomotor response (SMR score based on these three measured sudomotor parameters. A statistical analysis was performed using the analysis of variance to compare mean differences between the groups as well as receiver operating characteristic (ROC curves, to determine the specificity and sensitivity of SMR score to detect PDN, comparing the diabetic groups 1 and 2, and the coefficient of correlation between the CAN score and the SMR score in all the subjects included in the study.Results: When comparing the diabetes groups 1 and 2

  20. Treatment of painful diabetic neuropathy.

    Javed, Saad; Petropoulos, Ioannis N; Alam, Uazman; Malik, Rayaz A

    2015-01-01

    Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. Proposed pathogenetic treatments include α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage in diabetes) and aldose-reductase inhibitors (reduces flux through the polyol pathway). There is a growing need for studies to evaluate the most potent drugs or combinations for the management of PDN to maximize pain relief and improve quality of life. A number of agents are potential candidates for future use in PDN therapy, including Nav 1.7 antagonists, N-type calcium channel blockers, NGF antibodies and angiotensin II type 2 receptor antagonists. PMID:25553239

  1. Traumatic Optic Neuropathy - A Conundrum.

    Selvaraj, Vinoth Kanna; Viswanathan, Ramachandran; Devanathan, Vasudevan

    2016-03-01

    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

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

    ... Me Understand Genetics Home Health Conditions NARP neuropathy, ataxia, and retinitis pigmentosa Enable Javascript to view the ... Download PDF Open All Close All Description Neuropathy, ataxia, and retinitis pigmentosa ( NARP ) is a condition that ...

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

    Helmich, R.C.G.; Laarhoven, H.W.M. van; Schoonderwaldt, H.C.; Janssen, M.C.H.

    2009-01-01

    Rhabdomyolysis and peripheral neuropathy are two distinct disease entities which are rarely encountered in combination. We present a woman with rhabdomyolysis and peripheral neuropathy 3 weeks postpartum. Her symptoms were caused by bilateral femoral artery thrombosis due to postpartum cardiomyopath

  4. The Relationship between Dyslipidemia and Acute Axonal Function in Type 2 Diabetes Mellitus In Vivo

    Kwai, Natalie C. G.; Nigole, William; Poynten, Ann M.; Brown, Christopher; Krishnan, Arun V.

    2016-01-01

    Objectives Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of diabetes mellitus. Treatment largely consists of symptom alleviation and there is a need to identify therapeutic targets for prevention and treatment of DPN. The objective of this study was to utilise novel neurophysiological techniques to investigate axonal function in patients with type 2 diabetes and to prospectively determine their relationship to serum lipids in type 2 diabetic patients. Methods Seventy-one patients with type 2 diabetes were consecutively recruited and tested. All patients underwent thorough clinical neurological assessments including nerve conduction studies, and median motor axonal excitability studies. Studies were also undertaken in age matched normal control subjects(n = 42). Biochemical studies, including serum lipid levels were obtained in all patients. Patient excitability data was compared to control data and linear regression analysis was performed to determine the relationship between serum triglycerides and low density lipoproteins and excitability parameters typically abnormal in type 2 diabetic patients. Results Patient mean age was 64.2±2.3 years, mean glycosylated haemoglobin (HbA1c%) was 7.8±0.3%, mean triglyceride concentration was 1.6±0.1 mmol/L and mean cholesterol concentration was 4.1±0.2mmol/L. Compared to age matched controls, median motor axonal excitability studies indicated axonal dysfunction in type 2 diabetic patients as a whole (T2DM) and in a subgroup of the patients without DPN (T2DM-NN). These included reduced percentage threshold change during threshold electrotonus at 10–20ms depolarising currents (TEd10–20ms)(controls 68.4±0.8, T2DM63.9±0.8, T2DM-NN64.8±1.6%,Pdiabetic patients: TEd(10–20ms)(1.2(-1.4,3.8);P = 0.4) and superexcitability (2.4(-0.05, 4.8);P = 0.06). Conclusions These findings suggest that serum triglyceride levels are not related to axonal function in type 2 diabetic patients. Additional

  5. DIABETIC NEUROPATHY PART 2: PROXIMAL AND ASSYMMETRIC PHENOTYPES

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

    2013-01-01

    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 n...

  6. Health State Preference Assessment in Diabetic Peripheral Neuropathy

    Sullivan, Sean D.; Doris P. Lew; E. Beth Devine; Zafar Hakim; Gayle E. Reiber; Veenstra, David L.

    2002-01-01

    Objective: To assess patient preferences for health states associated with diabetic peripheral neuropathy (DPN). Design and intervention: Seven health states describing varying stages of disease severity in DPN were developed: mild neuropathy, painful neuropathy, severe neuropathy, minor ulcer, severe ulcer, minor amputation and major amputation. Using a computer interview, both rating scale (RS) and standard gamble (SG) preference scores were elicited from 52 patients with diabetes mellitus....

  7. Animal Models of Peripheral Neuropathy Due to Environmental Toxicants

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

    2014-01-01

    Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at...

  8. Femoral compressive neuropathy from iliopsoas haematoma complicating dengue hemorrhagic fever

    Sneha Ganu; Yesha Mehta

    2013-01-01

    Dengue fever is a debilitating mosquito-borne disease caused by dengue virus. We reported a case of femoral compression neuropathy due to iliopsoas hematoma complicating dengue hemorrhagic fever. Iliopsoas muscle hematoma can cause femoral neuropathy with resultant pain and paralysis. Such manifestations are not well documented in the literature. The pathogenesis of hematoma and compressive neuropathy with its appropriate management is discussed.

  9. Blood pressure regulation in diabetic autonomic neuropathy

    Hilsted, J

    1985-01-01

    Defective blood pressure responses to standing, exercise and epinephrine infusions have been demonstrated in diabetic patients with autonomic neuropathy. The circulatory mechanisms underlying blood pressure responses to exercise and standing up in these patients are well characterized: In both...... which may contribute to exercise hypotension in these patients. During hypoglycemia, blood pressure regulation seems intact in patients with autonomic neuropathy. This is probably due to release of substantial amounts of catecholamines during these experiments. During epinephrine infusions a substantial...... blood pressure fall ensues in patients with autonomic neuropathy, probably due to excessive muscular vasodilation. It is unresolved why blood pressure regulation is intact during hypoglycemia and severely impaired--at similar catecholamine concentrations--during epinephrine infusions....

  10. Enteric neuropathy associated to diabetes mellitus

    José Antonio Uranga-Ocio

    2015-06-01

    Full Text Available Diabetes mellitus (DM is a group of diseases highly prevalent nowadays. Its different types produce very similar symptoms with acute and chronic complications. Amongst these, gastrointestinal (GI dysmotility, associated with the development of neuropathy in the enteric nervous system (ENS is recognized. The objective is to review the current knowledge on GI dysmotility and enteric neuropathy associated to diabetes mellitus. The different functional and structural alterations within the digestive tract in diabetic patients and animal models are described. Finally, the therapeutic and preventive strategies tested so far in the context of enteric diabetic neuropathy are briefly summarized. In conclusion, amongst the alterations described in DM, the loss of inhibitory intrinsic innervation of the gut is most remarkable. Different therapeutic and/or preventive strategies, including the use of insulin, nerve growth factor or antioxidants, as well as myenteric neuron transplantation, are proposed.

  11. Biomarkers and surrogate endpoints in the glaucomatous optic neuropathy: new developments and a review

    Niro Kasahara

    2015-08-01

    Full Text Available ABSTRACT Glaucoma is a group of progressive optic neuropathies that have in common a slow progressive degeneration of retinal ganglion cells and their axons, resulting in a distinct appearance of the optic disc and a concomitant pattern of visual loss. Biomarkers are characteristics objectively measured and evaluated as indication of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Several biological markers have been implicated with glaucoma, especially genetics, proteomics, autoimmune and other molecular biomarkers, although, most awaits clinical validation. There are clear potential benefits in using biomarkers. Information can be obtained earlier, faster, and less costly. This review summarizes the latest developments and approaches in glaucoma biomarkers and its possible uses in the diagnosis, staging, and as predictors of response to treatment.

  12. [Ischemic optic neuropathy after lumbar spine surgery].

    Bermejo-Alvarez, M A; Carpintero, M; García-Carro, G; Acebal, G; Fervienza, P; Cosío, F

    2007-12-01

    Ischemic optic neuropathy is the most common cause of visual complications after non-ophthalmic surgery. The incidence has varied in different case series, but prone-position spine surgery appears to be involved in most of the reports. We present the case of a 47-year-old woman who developed near total blindness in the left eye following lumbar spine fusion surgery involving the loss of 900 mL of blood. An ophthalmic examination including inspection of the ocular fundus, fluorescein angiography, and visual evoked potentials returned a diagnosis of retrolaminar optic neuropathy. Outcome was poor. PMID:18200998

  13. Impairment of retrograde neuronal transport in oxaliplatin-induced neuropathy demonstrated by molecular imaging.

    Dawid Schellingerhout

    Full Text Available BACKGROUND AND PURPOSE: The purpose of our study was to utilize a molecular imaging technology based on the retrograde axonal transport mechanism (neurography, to determine if oxaliplatin-induced neurotoxicity affects retrograde axonal transport in an animal model. MATERIALS AND METHODS: Mice (n = 8/group were injected with a cumulative dose of 30 mg/kg oxaliplatin (sufficient to induce neurotoxicity or dextrose control injections. Intramuscular injections of Tetanus Toxin C-fragment (TTc labeled with Alexa 790 fluorescent dye were done (15 ug/20 uL in the left calf muscles, and in vivo fluorescent imaging performed (0-60 min at baseline, and then weekly for 5 weeks, followed by 2-weekly imaging out to 9 weeks. Tissues were harvested for immunohistochemical analysis. RESULTS: With sham treatment, TTc transport causes fluorescent signal intensity over the thoracic spine to increase from 0 to 60 minutes after injection. On average, fluorescence signal increased 722%+/-117% (Mean+/-SD from 0 to 60 minutes. Oxaliplatin treated animals had comparable transport at baseline (787%+/-140%, but transport rapidly decreased through the course of the study, falling to 363%+/-88%, 269%+/-96%, 191%+/-58%, 121%+/-39%, 75%+/-21% with each successive week and stabilizing around 57% (+/-15% at 7 weeks. Statistically significant divergence occurred at approximately 3 weeks (p≤0.05, linear mixed-effects regression model. Quantitative immuno-fluorescence histology with a constant cutoff threshold showed reduced TTc in the spinal cord at 7 weeks for treated animals versus controls (5.2 Arbitrary Units +/-0.52 vs 7.1 AU +/-1.38, p0.56, T-test. CONCLUSION: We show-for the first time to our knowledge-that neurographic in vivo molecular imaging can demonstrate imaging changes in a model of oxaliplatin-induced neuropathy. Impaired retrograde neural transport is suggested to be an important part of the pathophysiology of oxaliplatin-induced neuropathy.

  14. Loss of myelinated axons is specific to the central nervous system in a mouse model of the fetal alcohol syndrome.

    Parson, S H; Sojitra, N M

    1995-12-01

    We have previously developed a mouse model of the fetal alcohol syndrome, the outcome of which is a late loss of myelinated axons in the optic nerve of offspring of alcohol-treated mice between 9 and 15 wk of age. We have extended this study to investigate whether this axon loss is stable and specific to the central nervous system. Pregnant female (C57BL/6/Wlds x CBA) F1 mice were injected intraperitoneally with a single dose of a 25% solution of ethanol (v:w), on d 12 of gestation. Control animals were given a similar volume of saline at the same time. Litters were taken at 12 (n = 18) and 23 (n = 26) wk of age. Optic nerves only from 12-wk-old, and optic, tibial and saphenous nerves from 23-wk-old mice were removed. A systematic, random sampling method was used to estimate the cross-sectional area of whole nerves from semi thin sections, and the numbers and diameters of myelinated axons from ultrathin sections. There were no differences for the optic nerves of 12-wk-old alcohol-treated and control animals. Optic nerves from the alcohol-treated group at 23 wk had smaller cross-sectional areas and approximately 17% fewer myelinated axons than control nerves. These results confirm that axon loss occurs between 12 and 15 wk, and demonstrate that there is no additional loss of myelinated axons between 15 and 23 wk. In contrast, there were no significant differences in cross-sectional area, number of myelinated axons or axon calibre spectra for the tibial and saphenous nerves between the alcohol-treated and control groups. There was thus no evidence of a peripheral neuropathy as has been observed in chronic alcoholic subjects. In this 'binge' model of the fetal alcohol syndrome, a carefully timed dose of alcohol is administered during pregnancy to coincide with a critical period of development of the visual system. The result is a teratogenic effect which is specific to the central nervous system, stable and reproducible, with no obvious effect on the peripheral

  15. Diagnosis and therapeutic options for peripheral vasculitic neuropathy.

    Blaes, Franz

    2015-04-01

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

  16. Assessment of diabetic peripheral neuropathy in streptozotocin-induced diabetic rats with magnetic resonance imaging

    To determine the role of magnetic resonance (MR) imaging and quantitative T2 value measurements in the assessment of diabetic peripheral neuropathy (DPN). Sequential MR imaging, T2 measurement, and quantitative sensory testing of sciatic nerves were performed in streptozotocin-induced diabetic rats (n = 6) and normal control rats (n = 6) over a 7-week follow-up period. Histological assessment was obtained from 48 diabetic rats and 48 control rats once weekly for 7 weeks (n = 6 for each group at each time point). Nerve signal abnormalities were observed, and the T2 values, mechanical withdrawal threshold (MWT), and histological changes were measured and compared between diabetic and control animals. Sciatic nerves in the diabetic rats showed a gradual increase in T2 values beginning at 2 weeks after the induction (P = 0.014), while a decrease in MWT started at 3 weeks after the induction (P = 0.001). Nerve T2 values had a similar time course to sensory functional deficit in diabetic rats. Histologically, sciatic nerves of diabetic rats demonstrated obvious endoneural oedema from 2 to 3 weeks after the induction, followed by progressive axonal degeneration, Schwann cell proliferation, and coexistent disarranged nerve regeneration. Nerve T2 measurement is potentially useful in detecting and monitoring diabetic neuropathy. (orig.)

  17. Assessment of diabetic peripheral neuropathy in streptozotocin-induced diabetic rats with magnetic resonance imaging

    Wang, Dongye; Zhang, Xiang; Lu, Liejing; Li, Haojiang; Zhang, Fang; Chen, Yueyao; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong (China)

    2014-09-10

    To determine the role of magnetic resonance (MR) imaging and quantitative T2 value measurements in the assessment of diabetic peripheral neuropathy (DPN). Sequential MR imaging, T2 measurement, and quantitative sensory testing of sciatic nerves were performed in streptozotocin-induced diabetic rats (n = 6) and normal control rats (n = 6) over a 7-week follow-up period. Histological assessment was obtained from 48 diabetic rats and 48 control rats once weekly for 7 weeks (n = 6 for each group at each time point). Nerve signal abnormalities were observed, and the T2 values, mechanical withdrawal threshold (MWT), and histological changes were measured and compared between diabetic and control animals. Sciatic nerves in the diabetic rats showed a gradual increase in T2 values beginning at 2 weeks after the induction (P = 0.014), while a decrease in MWT started at 3 weeks after the induction (P = 0.001). Nerve T2 values had a similar time course to sensory functional deficit in diabetic rats. Histologically, sciatic nerves of diabetic rats demonstrated obvious endoneural oedema from 2 to 3 weeks after the induction, followed by progressive axonal degeneration, Schwann cell proliferation, and coexistent disarranged nerve regeneration. Nerve T2 measurement is potentially useful in detecting and monitoring diabetic neuropathy. (orig.)

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

    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 symmetri...

  19. Late onset Leber's optic neuropathy: a case confused with ischaemic optic neuropathy.

    Borruat, F X; Green, W T; Graham, E M; Sweeney, M G.; Morgan-Hughes, J A; Sanders, M D

    1992-01-01

    A case is reported of a 63-year-old man with progressive central visual loss in one eye followed 11 months later by involvement of the fellow eye. A diagnosis of chronic ischaemic optic neuropathy was considered. However, despite a negative family history, the absence of electrocardiographic abnormalities, and minimal fundus changes a diagnosis of Leber's optic neuropathy was made on the basis of magnetic resonance imaging findings and the mitochondrial DNA mutation at base pair 11778.

  20. Unusual presentation of hereditary neuropathy with liability to pressure palsies

    Andary Michael T

    2008-01-01

    Full Text Available Abstract Background Hereditary neuropathy with liability to pressure palsies (HNPP is an autosomal-dominant painless peripheral neuropathy characterized by episodes of repeated focal pressure neuropathies at sites of entrapment/compression, with a considerable variability in the clinical course. Electrodiagnostic and genetic testing are important in the diagnostic evaluation of these patients. Case presentation We report an unusual HNPP phenotype, five compression neuropathies in four nerves in a patient with bilateral hand numbness. A 42-year-old female, presented with acute bilateral paresthesias and weakness in her hands after starting yoga exercises requiring hyperextension of her hands at the wrists. Her presentation was complicated by: a a remote history of acute onset foot drop and subsequent improvement, b previous diagnoses of demyelinating peripheral neuropathy, possibly Charcot-Marie-Tooth disease, and c exposure to leprosy. Electrodiagnostic testing showed 5 separate compression neuropathies in 4 nerves including: severe left and right ulnar neuropathies at the wrist, left and right median neuropathies at the wrist and left ulnar neuropathy at the elbow. There was a mild generalized, primarily demyelinating, peripheral polyneuropathy. Based on the clinical suspicion and electrodiagnostic findings, consistent with profound demyelination in areas of compression, genetic analysis was done which identified a deletion of the PMP-22 gene consistent with HNPP. Conclusion HNPP can present with unusual phenotypes, such as 5 separate mononeuropathies, bilateral ulnar and median neuropathies at the wrists and ulnar neuropathy at the elbow with mild peripheral demyelinating polyneuropathy associated with the PMP-22 gene deletion.

  1. Cellular function of neuropathy target esterase in lysophosphatidylcholine action

    Neuropathy target esterase (NTE) plays critical roles in embryonic development and maintenance of peripheral axons. It is a secondary target of some organophosphorus toxicants including analogs of insecticides and chemical warfare agents. Although the mechanistic role of NTE in vivo is poorly defined, it is known to hydrolyze lysophosphatidylcholine (LPC) in vitro and may protect cell membranes from cytotoxic accumulation of LPC. To determine the cellular function of NTE, Neuro-2a and COS-7 cells were transfected with a full-length human NTE-containing plasmid yielding recombinant NTE (rNTE). We find the same inhibitor sensitivity and specificity profiles for rNTE assayed with LPC or phenyl valerate (a standard NTE substrate) and that this correlation extends to the LPC hydrolases of human brain, lymphocytes and erythrocytes. All of these LPC hydrolases are therefore very similar to each other in respect to a conserved inhibitor binding site conformation. NTE is expressed in brain and lymphocytes and contributes to LPC hydrolase activities in these tissues. The enzyme or enzymes responsible for erythrocyte LPC hydrolase activity remain to be identified. We also show that rNTE protects Neuro-2a and COS-7 cells from exogenous LPC cytotoxicity. Expression of rNTE in Neuro-2a cells alters their phospholipid balance (analyzed by liquid chromatography-mass spectrometry with single ion monitoring) by lowering LPC-16:0 and LPC-18:0 and elevating glycerophosphocholine without a change in phosphatidylcholine-16:0/18:1 or 16:0/18:2. NTE therefore serves an important function in LPC homeostasis and action

  2. Protein phosphorylation: Localization in regenerating optic axons

    A number of axonal proteins display changes in phosphorylation during goldfish optic nerve regeneration. (1) To determine whether the phosphorylation of these proteins was closely linked to their synthesis in the retinal ganglion cell body, cycloheximide was injected intraocularly into goldfish whose optic nerves had been regenerating for 3 weeks. Cycloheximide reduced the incorporation of [3H]proline and 32P orthophosphate into total nerve protein by 84% and 46%, respectively. Of the 20 individual proteins examined, 17 contained less than 15% of the [3H]proline label measured in corresponding controls, whereas 18 proteins contained 50% or more of the 32P label, suggesting that phosphorylation was largely independent of synthesis. (2) To determine whether the proteins were phosphorylated in the ganglion cell axons, axonal transport of proteins was blocked by intraocular injection of vincristine. Vincristine reduced [3H]proline labeling of total protein by 88% and 32P labeling by 49%. Among the individual proteins [3H]proline labeling was reduced by 90% or more in 18 cases but 32P labeling was reduced only by 50% or less. (3) When 32P was injected into the cranial cavity near the ends of the optic axons, all of the phosphoproteins were labeled more intensely in the optic tract than in the optic nerve. These results suggest that most of the major phosphoproteins that undergo changes in phosphorylation in the course of regeneration are phosphorylated in the optic axons

  3. How Schwann Cells Sort Axons: New Concepts.

    Feltri, M Laura; Poitelon, Yannick; Previtali, Stefano Carlo

    2016-06-01

    Peripheral nerves contain large myelinated and small unmyelinated (Remak) fibers that perform different functions. The choice to myelinate or not is dictated to Schwann cells by the axon itself, based on the amount of neuregulin I-type III exposed on its membrane. Peripheral axons are more important in determining the final myelination fate than central axons, and the implications for this difference in Schwann cells and oligodendrocytes are discussed. Interestingly, this choice is reversible during pathology, accounting for the remarkable plasticity of Schwann cells, and contributing to the regenerative potential of the peripheral nervous system. Radial sorting is the process by which Schwann cells choose larger axons to myelinate during development. This crucial morphogenetic step is a prerequisite for myelination and for differentiation of Remak fibers, and is arrested in human diseases due to mutations in genes coding for extracellular matrix and linkage molecules. In this review we will summarize progresses made in the last years by a flurry of reverse genetic experiments in mice and fish. This work revealed novel molecules that control radial sorting, and contributed unexpected ideas to our understanding of the cellular and molecular mechanisms that control radial sorting of axons. PMID:25686621

  4. Severe porphyric neuropathy--importance of screening for porphyria in Guillain-Barré syndrome.

    Schutte, Clara-Maria; van der Meyden, Cornelius H; van Niekerk, Linette; Kakaza, Mandisa; van Coller, Riaan; Ueckermann, Veronica; Oosthuizen, Nicky M

    2016-01-01

    The hepatic porphyrias are a group of rare metabolic disorders, each of which is associated with a specific enzymatic alteration in the haem biosynthesis pathway. In South Africa (SA), a high incidence of variegate porphyria (VP) is seen as a result of a founder effect, but acute intermittent porphyria (AIP) is also encountered. The development of acute neurovisceral attacks is related to environmental factors, including medications, hormones and diet. A possible manifestation of a severe attack is rapidly progressing quadriparesis, which may mimic Guillain-Barré syndrome. We present four such cases, highlighting that acute porphyria should be considered in the differential diagnosis of Guillain-Barré syndrome. Three patients presented to Steve Biko Academic Hospital, Pretoria, SA, with progressive quadriparesis, and one to a private hospital with acute abdominal pain followed by rapidly progressive quadriparesis. Two patients had started antiretroviral therapy before the development of symptoms, and one had started antituberculosis therapy. All patients had marked weakness with depressed reflexes, and showed varying degrees of confusion. An initial diagnosis of Guillain-Barré syndrome led to administration of intravenous immunoglobulins in two patients. On testing for porphyria, it was found that two patients had AIP and two VP. Electrophysiological investigations revealed severe mainly motor axonal neuropathy in all. Two patients deteriorated to the point of requiring mechanical ventilation, and one of them died due to complications of critical illness. Haemin was administered to three patients, but the process of obtaining this medication was slow, which delayed the recommended early administration. The surviving patients showed minimal recovery and remained severely disabled. Porphyric neuropathy should always be considered as a differential diagnosis in a patient with an acute neuropathy, especially in SA. Absence of abdominal pain does not exclude the

  5. Calpain activity promotes the sealing of severed giant axons

    Godell, Christopher M.; Smyers, Mark E.; Eddleman, Christopher S.; Ballinger, Martis L.; Fishman, Harvey M.; Bittner, George D.

    1997-01-01

    A barrier (seal) must form at the cut ends of a severed axon if a neuron is to survive and eventually regenerate. Following severance of crayfish medial giant axons in physiological saline, vesicles accumulate at the cut end and form a barrier (seal) to ion and dye diffusion. In contrast, squid giant axons do not seal, even though injury-induced vesicles form after axonal transection and accumulate at cut axonal ends. Neither axon seals in Ca2+-free salines. The addition of calpain to the bat...

  6. Idiopathic trigeminal neuropathy in a poodle

    Carlos Eduardo Aparicio

    2010-12-01

    Full Text Available A seven years old, male poodle is examined presenting acute mandible paralysis (dropped jaw, drooling and difficulty for the apprehension and chewing; not evidence of an other alteration of cranial nerves. The muscular biopsy rules out a myositisof masticatory muscles. The disorder is resolved completely in 3 weeks confirming diagnosis of idiopathic trigeminal neuropathy.

  7. Suboccipital neuropathy after bone conduction device placement

    Faber, H.T.; Ru, J.A. de

    2013-01-01

    OBJECTIVE: To describe the clinical characteristics of a 70-year-old female with occipital neuropathy following bone conduction device surgery. DESCRIPTION: A 65-year-old woman underwent bone conduction device placement surgery on the left temporal bone. Postoperatively she progressively developed c

  8. Poisoning by organophosphorus insecticides and sensory neuropathy

    Moretto, A; M. Lotti

    1998-01-01

    OBJECTIVES—Poisoning by organophosphate insecticides causes cholinergic toxicity. Organophosphate induced delayed polyneuropathy (OPIDP) is a sensory-motor distal axonopathy which usually occurs after ingestion of large doses of certain organophosphate insecticides and has so far only been reported in patients with preceding cholinergic toxicity. Surprisingly, it was recently reported by other authors that an exclusively sensory neuropathy developed in eight patients afte...

  9. Microfluidic device for unidirectional axon growth

    Malishev, E.; Pimashkin, A.; Gladkov, A.; Pigareva, Y.; Bukatin, A.; Kazantsev, V.; Mukhina, I.; Dubina, M.

    2015-11-01

    In order to better understand the communication and connectivity development of neuron networks, we designed microfluidic devices with several chambers for growing dissociated neuronal cultures from mice fetal hippocampus (E18). The chambers were connected with microchannels providing unidirectional axonal growth between “Source” and “Target” neural sub-networks. Experiments were performed in a hippocampal cultures plated in a poly-dimethylsiloxane (PDMS) microfluidic chip, aligned with a 60 microelectrode array (MEA). Axonal growth through microchannels was observed with brightfield, phase-contrast and fluorescence microscopy, and after 7 days in vitro electrical activity was recorded. Visual inspection and spike propagation analysis showed the predominant axonal growth in microchannels in a direction from “Source” to “Target”.

  10. Diverse modes of axon elaboration in the developing neocortex.

    2005-08-01

    Full Text Available The development of axonal arbors is a critical step in the establishment of precise neural circuits, but relatively little is known about the mechanisms of axonal elaboration in the neocortex. We used in vivo two-photon time-lapse microscopy to image axons in the neocortex of green fluorescent protein-transgenic mice over the first 3 wk of postnatal development. This period spans the elaboration of thalamocortical (TC and Cajal-Retzius (CR axons and cortical synaptogenesis. Layer 1 collaterals of TC and CR axons were imaged repeatedly over time scales ranging from minutes up to days, and their growth and pruning were analyzed. The structure and dynamics of TC and CR axons differed profoundly. Branches of TC axons terminated in small, bulbous growth cones, while CR axon branch tips had large growth cones with numerous long filopodia. TC axons grew rapidly in straight paths, with frequent interstitial branch additions, while CR axons grew more slowly along tortuous paths. For both types of axon, new branches appeared at interstitial sites along the axon shaft and did not involve growth cone splitting. Pruning occurred via retraction of small axon branches (tens of microns, at both CR and TC axons or degeneration of large portions of the arbor (hundreds of microns, for TC axons only. The balance between growth and retraction favored overall growth, but only by a slight margin. Given the identical layer 1 territory upon which CR and TC axons grow, the differences in their structure and dynamics likely reflect distinct intrinsic growth programs for axons of long projection neurons versus local interneurons.

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

    James Gilchrist

    2012-08-01

    Full Text Available 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.

  12. Automated Axon Counting in Rodent Optic Nerve Sections with AxonJ

    Zarei, Kasra; Scheetz, Todd E.; Christopher, Mark; Miller, Kathy; Hedberg-Buenz, Adam; Tandon, Anamika; Anderson, Michael G.; Fingert, John H.; Abràmoff, Michael David

    2016-01-01

    We have developed a publicly available tool, AxonJ, which quantifies the axons in optic nerve sections of rodents stained with paraphenylenediamine (PPD). In this study, we compare AxonJ’s performance to human experts on 100x and 40x images of optic nerve sections obtained from multiple strains of mice, including mice with defects relevant to glaucoma. AxonJ produced reliable axon counts with high sensitivity of 0.959 and high precision of 0.907, high repeatability of 0.95 when compared to a gold-standard of manual assessments and high correlation of 0.882 to the glaucoma damage staging of a previously published dataset. AxonJ allows analyses that are quantitative, consistent, fully-automated, parameter-free, and rapid on whole optic nerve sections at 40x. As a freely available ImageJ plugin that requires no highly specialized equipment to utilize, AxonJ represents a powerful new community resource augmenting studies of the optic nerve using mice. PMID:27226405

  13. Axonal transport of ribonucleoprotein particles (vaults).

    Li, J Y; Volknandt, W; Dahlstrom, A; Herrmann, C; Blasi, J; Das, B; Zimmermann, H

    1999-01-01

    RNA was previously shown to be transported into both dendritic and axonal compartments of nerve cells, presumably involving a ribonucleoprotein particle. In order to reveal potential mechanisms of transport we investigated the axonal transport of the major vault protein of the electric ray Torpedo marmorata. This protein is the major protein component of a ribonucleoprotein particle (vault) carrying a non-translatable RNA and has a wide distribution in the animal kingdom. It is highly enriched in the cholinergic electromotor neurons and similar in size to synaptic vesicles. The axonal transport of vaults was investigated by immunofluorescence, using the anti-vault protein antibody as marker, and cytofluorimetric scanning, and was compared to that of the synaptic vesicle membrane protein SV2 and of the beta-subunit of the F1-ATPase as a marker for mitochondria. Following a crush significant axonal accumulation of SV2 proximal to the crush could first be observed after 1 h, that of mitochondria after 3 h and that of vaults after 6 h, although weekly fluorescent traces of accumulations of vault protein were observed in the confocal microscope as early as 3 h. Within the time-period investigated (up to 72 h) the accumulation of all markers increased continuously. Retrograde accumulations also occurred, and the immunofluorescence for the retrograde component, indicating recycling, was weaker than that for the anterograde component, suggesting that more than half of the vaults are degraded within the nerve terminal. High resolution immunofluorescence revealed a granular structure-in accordance with the biochemical characteristics of vaults. Of interest was the observation that the increase of vault immunoreactivity proximal to the crush accelerated with time after crushing, while that of SV2-containing particles appeared to decelerate, indicating that the crush procedure with time may have induced perikaryal alterations in the production and subsequent export to the axon

  14. MSC p43 required for axonal development in motor neurons

    Zhu, Xiaodong; Liu, Yang; Yin, Yanqing; Shao, Aiyun; Zhang, Bo; Kim, Sunghoon; Zhou, Jiawei

    2009-01-01

    Neuron connectivity and correct neural function largely depend on axonal integrity. Neurofilaments (NFs) constitute the main cytoskeletal network maintaining the structural integrity of neurons and exhibit dynamic changes during axonal and dendritic growth. However, the mechanisms underlying axonal development and maintenance remain poorly understood. Here, we identify that multisynthetase complex p43 (MSC p43) is essential for NF assembly and axon maintenance. The MSC p43 protein was predominantly expressed in central neurons and interacted with NF light subunit in vivo. Mice lacking MSC p43 exhibited axon degeneration in motor neurons, defective neuromuscular junctions, muscular atrophy, and motor dysfunction. Furthermore, MSC p43 depletion in mice caused disorganization of the axonal NF network. Mechanistically, MSC p43 is required for maintaining normal phosphorylation levels of NFs. Thus, MSC p43 is indispensable in maintaining axonal integrity. Its dysfunction may underlie the NF disorganization and axon degeneration associated with motor neuron degenerative diseases. PMID:19717447

  15. Functions of axon guidance molecules in synapse formation

    Chen, Shih-Yu; Cheng, Hwai-Jong

    2009-01-01

    Axon guidance and synapse formation are important developmental events for establishing a functional neuronal circuitry. These two related cellular processes occur in a coordinated fashion but previous studies from multiple model organisms seemed to suggest that axon guidance and synapse formation are mediated by distinct molecular cues. Thus, axon guidance molecules are responsible for guiding the navigating axon toward its target area, while other adhesion or ligand-receptor molecules speci...

  16. Morphometry of Axons in Optic Nerves of Siamese's Twins

    Xinzu Gu; Zhenping Zhang; Qi Lin; Jiongji Liang; Wenyu Lu; Xiulan Ye; A A Sadun

    2002-01-01

    Purpose: To observe the development of optic nerve, we examined four optic nerves from Siameses Twins by absolute counts of axons.Methods: Mean axon diameter, mean axon density, totally axonal population and optic nerve area were noted for each optic nerve. The mean axon diameter and the mean axon density were compared between paraxial (inner sectors)and cortical (outer sectors)areas of the nerves.Results: More myelinated axons were seen in the inner sectors as compared to the outer sectors(average 11 axons/1 000 μm2 in inner sectors and 34 axons/l 000 μm2 in outer sectors( P=0. 036) . The myelinated fibers were also smaller(63 microns) in the outer sectors as compared to the inner sectors(72 microns) ( P = 0. 001 ). The average cross sectors area for the four 40 week stage optical nerves of Siamese Twins was 3.32 × 103 as compared to 1 million axons for 32-week-old normals.Conclusion: Our finding of fewer axonal number and small myelinated fibers in the Siamese Twins suggests hypoplasia. Myelination was more abnormal in the paraxial optic nerve than that in the peripheral sectors, suggesting anomalous development of optic nerve peripherally and delayed developnent centrally. Axonal density is higher in inner sectors than that in outer sectors, suggesting delayed development of the outer nerve sector.

  17. Electrokinetic confinement of axonal growth for dynamically configurable neural networks.

    Honegger, Thibault; Scott, Mark A; Yanik, Mehmet F; Voldman, Joel

    2013-02-21

    Axons in the developing nervous system are directed via guidance cues, whose expression varies both spatially and temporally, to create functional neural circuits. Existing methods to create patterns of neural connectivity in vitro use only static geometries, and are unable to dynamically alter the guidance cues imparted on the cells. We introduce the use of AC electrokinetics to dynamically control axonal growth in cultured rat hippocampal neurons. We find that the application of modest voltages at frequencies on the order of 10(5) Hz can cause developing axons to be stopped adjacent to the electrodes while axons away from the electric fields exhibit uninhibited growth. By switching electrodes on or off, we can reversibly inhibit or permit axon passage across the electrodes. Our models suggest that dielectrophoresis is the causative AC electrokinetic effect. We make use of our dynamic control over axon elongation to create an axon-diode via an axon-lock system that consists of a pair of electrode 'gates' that either permit or prevent axons from passing through. Finally, we developed a neural circuit consisting of three populations of neurons, separated by three axon-locks to demonstrate the assembly of a functional, engineered neural network. Action potential recordings demonstrate that the AC electrokinetic effect does not harm axons, and Ca(2+) imaging demonstrated the unidirectional nature of the synaptic connections. AC electrokinetic confinement of axonal growth has potential for creating configurable, directional neural networks. PMID:23314575

  18. Spatial temperature gradients guide axonal outgrowth

    Black, Bryan; Vishwakarma, Vivek; Dhakal, Kamal; Bhattarai, Samik; Pradhan, Prabhakar; Jain, Ankur; Kim, Young-Tae; Mohanty, Samarendra

    2016-07-01

    Formation of neural networks during development and regeneration after injury depends on accuracy of axonal pathfinding, which is primarily believed to be influenced by chemical cues. Recently, there is growing evidence that physical cues can play crucial role in axonal guidance. However, detailed mechanism involved in such guidance cues is lacking. By using weakly-focused near-infrared continuous wave (CW) laser microbeam in the path of an advancing axon, we discovered that the beam acts as a repulsive guidance cue. Here, we report that this highly-effective at-a-distance guidance is the result of a temperature field produced by the near-infrared laser light absorption. Since light absorption by extracellular medium increases when the laser wavelength was red shifted, the threshold laser power for reliable guidance was significantly lower in the near-infrared as compared to the visible spectrum. The spatial temperature gradient caused by the near-infrared laser beam at-a-distance was found to activate temperature-sensitive membrane receptors, resulting in an influx of calcium. The repulsive guidance effect was significantly reduced when extracellular calcium was depleted or in the presence of TRPV1-antagonist. Further, direct heating using micro-heater confirmed that the axonal guidance is caused by shallow temperature-gradient, eliminating the role of any non-photothermal effects.

  19. Axonal PPARγ promotes neuronal regeneration after injury.

    Lezana, Juan Pablo; Dagan, Shachar Y; Robinson, Ari; Goldstein, Ronald S; Fainzilber, Mike; Bronfman, Francisca C; Bronfman, Miguel

    2016-06-01

    PPARγ is a ligand-activated nuclear receptor best known for its involvement in adipogenesis and glucose homeostasis. PPARγ activity has also been associated with neuroprotection in different neurological disorders, but the mechanisms involved in PPARγ effects in the nervous system are still unknown. Here we describe a new functional role for PPARγ in neuronal responses to injury. We found both PPAR transcripts and protein within sensory axons and observed an increase in PPARγ protein levels after sciatic nerve crush. This was correlated with increased retrograde transport of PPARγ after injury, increased association of PPARγ with the molecular motor dynein, and increased nuclear accumulation of PPARγ in cell bodies of sensory neurons. Furthermore, PPARγ antagonists attenuated the response of sensory neurons to sciatic nerve injury, and inhibited axonal growth of both sensory and cortical neurons in culture. Thus, axonal PPARγ is involved in neuronal injury responses required for axonal regeneration. Since PPARγ is a major molecular target of the thiazolidinedione (TZD) class of drugs used in the treatment of type II diabetes, several pharmaceutical agents with acceptable safety profiles in humans are available. Our findings provide motivation and rationale for the evaluation of such agents for efficacy in central and peripheral nerve injuries. PMID:26446277

  20. Early cellular signaling responses to axonal injury

    Wang Ai

    2009-03-01

    Full Text Available Abstract Background We have used optic nerve injury as a model to study early signaling events in neuronal tissue following axonal injury. Optic nerve injury results in the selective death of retinal ganglion cells (RGCs. The time course of cell death takes place over a period of days with the earliest detection of RGC death at about 48 hr post injury. We hypothesized that in the period immediately following axonal injury, there are changes in the soma that signal surrounding glia and neurons and that start programmed cell death. In the current study, we investigated early changes in cellular signaling and gene expression that occur within the first 6 hrs post optic nerve injury. Results We found evidence of cell to cell signaling within 30 min of axonal injury. We detected differences in phosphoproteins and gene expression within the 6 hrs time period. Activation of TNFα and glutamate receptors, two pathways that can initiate cell death, begins in RGCs within 6 hrs following axonal injury. Differential gene expression at 6 hrs post injury included genes involved in cytokine, neurotrophic factor signaling (Socs3 and apoptosis (Bax. Conclusion We interpret our studies to indicate that both neurons and glia in the retina have been signaled within 30 min after optic nerve injury. The signals are probably initiated by the RGC soma. In addition, signals activating cellular death pathways occur within 6 hrs of injury, which likely lead to RGC degeneration.

  1. Patterns of growth, axonal extension and axonal arborization of neuronal lineages in the developing Drosophila brain

    Larsen, Camilla; Shy, Diana; Spindler, Shana R; Fung, Siaumin; Pereanu, Wayne; Younossi -Hartenstein, Amelia; Hartenstein, Volker

    2009-01-01

    The Drosophila central brain is composed of approximately 100 paired lineages, with most lineages comprising 100–150 neurons. Most lineages have a number of important characteristics in common. Typically, neurons of a lineage stay together as a coherent cluster and project their axons into a coherent bundle visible from late embryo to adult. Neurons born during the embryonic period form the primary axon tracts (PATs) that follow stereotyped pathways in the neuropile. Apoptotic cell death remo...

  2. Diagnosing ulnar neuropathy at the elbow using magnetic resonance neurography

    Early diagnosis of ulnar neuropathy at the elbow is important. Magnetic resonance neurography (MRN) images peripheral nerves. We evaluated the usefulness of elbow MRN in diagnosing ulnar neuropathy at the elbow. The MR neurograms of 21 patients with ulnar neuropathy were reviewed retrospectively. MRN was performed prospectively on 10 normal volunteers. The MR neurograms included axial T1 and axial T2 fat-saturated and/or axial STIR sequences. The sensitivity and specificity of MRN in detecting ulnar neuropathy were determined. The mean ulnar nerve size in the symptomatic and normal groups was 0.12 and 0.06 cm2 (P 2, sensitivity was 95% and specificity was 80%. Ulnar nerve size and signal intensity were greater in patients with ulnar neuropathy. MRN is a useful test in evaluating ulnar neuropathy at the elbow. (orig.)

  3. Tumefactive Brain Demyelination Accompanying MADSAM Neuropathy

    Şefik Evren Erdener

    2015-09-01

    Full Text Available Multifocal acquired demyelinating sensory and motor (MADSAM neuropathy is characterized by asymmetric multifocal motor and sensory loss and conduction blocks in peripheral nerves. Peripheral demyelinating diseases may be accompanied by demyelination in central nervous system (CNS. In this report, a MADSAM patient with a solitary tumefactive demyelinating lesion in brain is presented. Neuroimaging due to a visual field defect revealed a right parietooccipital lesion, which was initially misdiagnosed as a tumor. Pathological examination showed that it was demyelinating in nature. Peripheral nervous symptoms of the patient developed two years later and she was then diagnosed with MADSAM. There was prominent clinical and electrophysiological response to steroid treatment. Tumefactive brain involvement was not previously reported for MADSAM neuropathy, although it was documented in a single case with typical chronic inflammatory demyelinating polyneuropathy (CIDP. CNS involvement should therefore be considered in MADSAM patients.

  4. Suprascapular Nerve Neuropathy: A Case Report

    Cengiz BAHADIR

    2008-10-01

    Full Text Available Isolated suprascapular nerve ınjury is rarely seen. It may cause shoulder pain and functional limitation. This neuropathy should be considered in the differential diagnosis of shoulder pain with glenohumeral instability, rotator cuff disease, cervical radiculopathies, tendinitis, adhesive capsulitis, trauma and degenerative disease. Trauma, repetitive abnormal motions of scapula and iatrogenic causes take place in etiology. Injury of the nerve due to traction and elongation is the most probable pathomechanism. Shoulder pain and limitation of motion are the symptoms that may help to define the nerve damage before devoloping muscle atrophy. While tumoral lesions that can cause nerve entrapment and avulsions due to traction are treated surgically; overuse and elongation ınjuries are treated with physical theraphy modalities. In this report, a case with the complaints of shoulder pain and weakness due to isolated suprascapular neuropathy was discussed. Turk J Phys Med Rehab 2008;54:118-21.

  5. Cardiovascular autonomic neuropathy in the diabetic patients.

    Maria Eugenia Niño Mantilla

    2007-11-01

    Full Text Available the dysfunction of the autonomic nervous system is a serious problem in diabetic patients. The cardiovacular autonomic neuropathy is the most important autonomic dysfuntion for it´s implication in the increasesof the mortality rate in diabetis patients. tis ethiopatogenesis is the result of a multifactorial process caused by chronic hyperglycemia, ending up in damage of the autonomic fibers thet innervate the heart and blood vessels, leading to dysfuntional hearth rate control and abnormal vascular dynamics. the associated clinical manifestations include orthotatic hypotension, excecise intolerance, intraoperative cardiovascular liability and silent myocardial ischemia. Being important its recognition, quantitative test to evaluate the cardiovascular funtion, to value its evolution and the effects of the treatment ahould be done, being the most used, the hearth rate response to standing test, and teh valsalva maneuver. the handling of this entity is done improving control of glucose blood levels its the most effective way to prevent the cardiovascular autonomic neuropathy in the diabetic patients.

  6. White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis

    Cambron, Melissa; D'Haeseleer, Miguel; Laureys, Guy; Clinckers, Ralph; Debruyne, Jan; De Keyser, Jacques

    2012-01-01

    In patients with multiple sclerosis (MS), a diffuse axonal degeneration occurring throughout the white matter of the central nervous system causes progressive neurologic disability. The underlying mechanism is unclear. This review describes a number of pathways by which dysfunctional astrocytes in MS might lead to axonal degeneration. White-matter astrocytes in MS show a reduced metabolism of adenosine triphosphate-generating phosphocreatine, which may impair the astrocytic sodium potassium pump and lead to a reduced sodium-dependent glutamate uptake. Astrocytes in MS white matter appear to be deficient in β2 adrenergic receptors, which are involved in stimulating glycogenolysis and suppressing inducible nitric oxide synthase (NOS2). Glutamate toxicity, reduced astrocytic glycogenolysis leading to reduced lactate and glutamine production, and enhanced nitric oxide (NO) levels may all impair axonal mitochondrial metabolism, leading to axonal degeneration. In addition, glutamate-mediated oligodendrocyte damage and impaired myelination caused by a decreased production of N-acetylaspartate by axonal mitochondria might also contribute to axonal loss. White-matter astrocytes may be considered as a potential target for neuroprotective MS therapies. PMID:22214904

  7. Mislocalization of neuronal mitochondria reveals regulation of Wallerian degeneration and NMNAT/WLDS-mediated axon protection independent of axonal mitochondria

    Kitay, Brandon M.; McCormack, Ryan; Wang, Yunfang; Tsoulfas, Pantelis; Zhai, R. Grace

    2013-01-01

    Axon degeneration is a common and often early feature of neurodegeneration that correlates with the clinical manifestations and progression of neurological disease. Nicotinamide mononucleotide adenylytransferase (NMNAT) is a neuroprotective factor that delays axon degeneration following injury and in models of neurodegenerative diseases suggesting a converging molecular pathway of axon self-destruction. The underlying mechanisms have been under intense investigation and recent reports suggest...

  8. AxonQuant: A Microfluidic Chamber Culture-Coupled Algorithm That Allows High-Throughput Quantification of Axonal Damage

    Yang Li

    2014-02-01

    Full Text Available Published methods for imaging and quantitatively analyzing morphological changes in neuronal axons have serious limitations because of their small sample sizes, and their time-consuming and nonobjective nature. Here we present an improved microfluidic chamber design suitable for fast and high-throughput imaging of neuronal axons. We developed the AxonQuant algorithm, which is suitable for automatic processing of axonal imaging data. This microfluidic chamber-coupled algorithm allows calculation of an ‘axonal continuity index' that quantitatively measures axonal health status in a manner independent of neuronal or axonal density. This method allows quantitative analysis of axonal morphology in an automatic and nonbiased manner. Our method will facilitate large-scale high-throughput screening for genes or therapeutic compounds for neurodegenerative diseases involving axonal damage. When combined with imaging technologies utilizing different gene markers, this method will provide new insights into the mechanistic basis for axon degeneration. Our microfluidic chamber culture-coupled AxonQuant algorithm will be widely useful for studying axonal biology and neurodegenerative disorders. © 2014 S. Karger AG, Basel

  9. Traumatic neuropathy of second cervical spinal nerves.

    Behrman, S

    1983-01-01

    The second cervical spinal nerves are unduly vulnerable to forcible approximation of the arches of the atlas and axis and to excessive rotation of the atlas on the axis. Sequelae of such injury include sensory aberrations ranging from loss of feeling to severe neuralgia and disorders of balance. Diagnosis of second cervical neuropathy may be difficult when there are multiple injuries to the cervical spine, but most cases clear up spontaneously within one to three years.

  10. Infectious optic neuropathies: a clinical update

    Kahloun R; Abroug N; Ksiaa I; Mahmoud A; Zeghidi H; Zaouali S; Khairallah M

    2015-01-01

    Rim Kahloun, Nesrine Abroug, Imen Ksiaa, Anis Mahmoud, Hatem Zeghidi, Sonia Zaouali, Moncef KhairallahDepartment of Ophthalmology, Fattouma Bourguiba University Hospital, Faculty of Medicine, University of Monastir, Monastir, TunisiaAbstract: Different forms of optic neuropathy causing visual impairment of varying severity have been reported in association with a wide variety of infectious agents. Proper clinical diagnosis of any of these infectious conditions is based on epidemiological data...

  11. Cranial nerve involvement in patients with leprous neuropathy

    Kumar Sudhir; Alexander Mathew; Gnanamuthu Chandran

    2006-01-01

    Background: Leprosy is one of the most common causes of peripheral neuropathy, perhaps closely matched by diabetic neuropathy. Patterns of peripheral neuropathy in leprosy can be varied, which may include mononeuropathy, mononeuritis multiplex and symmetric polyneuropathy. Cranial nerves, especially facial and trigeminal nerves, are also commonly involved in leprosy. Aims: To find out the pattern and spectrum of cranial nerve involvement in a consecutive series of patients with leprous neu...

  12. Optic neuropathy in a patient with pyruvate dehydrogenase deficiency

    Small, Juan E. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Gonzalez, Guido E. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States); Clinica Alemana de Santiago, Departmento de Imagenes, Santiago (Chile); Nagao, Karina E.; Walton, David S. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Ophthalmology, Boston, MA (United States); Caruso, Paul A. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2009-10-15

    Pyruvate dehydrogenase (PDH) deficiency is a genetic disorder of mitochondrial metabolism. The clinical manifestations range from severe neonatal lactic acidosis to chronic neurodegeneration. Optic neuropathy is an uncommon clinical sequela and the imaging findings of optic neuropathy in these patients have not previously been described. We present a patient with PDH deficiency with bilateral decreased vision in whom MRI demonstrated bilateral optic neuropathy and chiasmopathy. (orig.)

  13. The role of autonomic neuropathy in diabetic foot ulceration.

    M.E. Ahmed; Delbridge, L; Le Quesne, L P

    1986-01-01

    Five standard, non-invasive tests of cardiovascular, autonomic function were performed in each of four groups of 30 subjects: controls, group 1, diabetics without clinical evidence of neuropathy; group 2, diabetics with neuropathy, but without foot ulceration; group 3, diabetics with neuropathic ulceration of the foot. The results showed a significant impairment of autonomic function in diabetics without clinically demonstrable somatic neuropathy compared with controls diabetics with somatic ...

  14. Diagnosis and therapeutic options for peripheral vasculitic neuropathy

    Blaes, Franz

    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, ...

  15. Auditory Neuropathy Spectrum Disorder Masquerading as Social Anxiety

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

    2015-01-01

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

  16. Effect of Tinospora cordifolia on experimental diabetic neuropathy

    Pratibha D Nadig

    2012-01-01

    Conclusions: Tinospora cordifolia prevents the hyperalgesia in experimental diabetic neuropathy. It has an aldose reductase inhibitory activity in-vitro which may contribute to the beneficial effects.

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

    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. PMID:23642718

  18. Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases

    Fang Cheng

    2012-06-01

    Full Text Available Abstract Background Reactive oxygen species (ROS released by microglia and other inflammatory cells can cause axonal degeneration. A reduction in axonal transport has also been implicated as a cause of axonal dystrophies and neurodegeneration, but there is a paucity of experimental data concerning the effects of ROS on axonal transport. We used live cell imaging to examine the effects of hydrogen peroxide on the axonal transport of mitochondria and Golgi-derived vesicles in cultured rat hippocampal neurons. Results Hydrogen peroxide rapidly inhibited axonal transport, hours before any detectable changes in mitochondrial morphology or signs of axonal degeneration. Mitochondrial transport was affected earlier and was more severely inhibited than the transport of Golgi-derived vesicles. Anterograde vesicle transport was more susceptible to peroxide inhibition than retrograde transport. Axonal transport partially recovered following removal of hydrogen peroxide and local application of hydrogen peroxide inhibited transport, suggesting that the effects were not simply a result of nerve cell death. Sodium azide, an ATP synthesis blocker, had similar effects on axonal transport, suggesting that ATP depletion may contribute to the transport inhibition due to hydrogen peroxide. Conclusions These results indicate that inhibition of axonal transport is an early consequence of exposure to ROS and may contribute to subsequent axonal degeneration.

  19. Axon Membrane Skeleton Structure is Optimized for Coordinated Sodium Propagation

    Zhang, Yihao; Li, He; Tzingounis, Anastasios V; Lykotrafitis, George

    2016-01-01

    Axons transmit action potentials with high fidelity and minimal jitter. This unique capability is likely the result of the spatiotemporal arrangement of sodium channels along the axon. Super-resolution microscopy recently revealed that the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under entropic tension. Sodium channels also exhibit a periodic distribution pattern, as they bind to ankyrin G, which associates with spectrin. Here, we elucidate the relationship between the axon membrane skeleton structure and the function of the axon. By combining cytoskeletal dynamics and continuum diffusion modeling, we show that spectrin filaments under tension minimize the thermal fluctuations of sodium channels and prevent overlap of neighboring channel trajectories. Importantly, this axon skeletal arrangement allows for a highly reproducible band-like activation of sodium channels leading to coordinated sodium propagation along the axon.

  20. Axon position within the corpus callosum determines contralateral cortical projection.

    Zhou, Jing; Wen, Yunqing; She, Liang; Sui, Ya-Nan; Liu, Lu; Richards, Linda J; Poo, Mu-Ming

    2013-07-16

    How developing axons in the corpus callosum (CC) achieve their homotopic projection to the contralateral cortex remains unclear. We found that axonal position within the CC plays a critical role in this projection. Labeling of nearby callosal axons in mice showed that callosal axons were segregated in an orderly fashion, with those from more medial cerebral cortex located more dorsally and subsequently projecting to more medial contralateral cortical regions. The normal axonal order within the CC was grossly disturbed when semaphorin3A/neuropilin-1 signaling was disrupted. However, the order in which axons were positioned within the CC still determined their contralateral projection, causing a severe disruption of the homotopic contralateral projection that persisted at postnatal day 30, when the normal developmental refinement of contralateral projections is completed in wild-type (WT) mice. Thus, the orderly positioning of axons within the CC is a primary determinant of how homotopic interhemispheric projections form in the contralateral cortex. PMID:23812756

  1. Synaptic Democracy and Vesicular Transport in Axons

    Bressloff, Paul C.; Levien, Ethan

    2015-04-01

    Synaptic democracy concerns the general problem of how regions of an axon or dendrite far from the cell body (soma) of a neuron can play an effective role in neuronal function. For example, stimulated synapses far from the soma are unlikely to influence the firing of a neuron unless some sort of active dendritic processing occurs. Analogously, the motor-driven transport of newly synthesized proteins from the soma to presynaptic targets along the axon tends to favor the delivery of resources to proximal synapses. Both of these phenomena reflect fundamental limitations of transport processes based on a localized source. In this Letter, we show that a more democratic distribution of proteins along an axon can be achieved by making the transport process less efficient. This involves two components: bidirectional or "stop-and-go" motor transport (which can be modeled in terms of advection-diffusion), and reversible interactions between motor-cargo complexes and synaptic targets. Both of these features have recently been observed experimentally. Our model suggests that, just as in human societies, there needs to be a balance between "efficiency" and "equality".

  2. Psychophysical testing in rodent models of glaucomatous optic neuropathy.

    Grillo, Stephanie L; Koulen, Peter

    2015-12-01

    Processing of visual information begins in the retina, with photoreceptors converting light stimuli into neural signals. Ultimately, signals are transmitted to the brain through signaling networks formed by interneurons, namely bipolar, horizontal and amacrine cells providing input to retinal ganglion cells (RGCs), which form the optic nerve with their axons. As part of the chronic nature of glaucomatous optic neuropathy, the increasing and irreversible damage and ultimately loss of neurons, RGCs in particular, occurs following progressive damage to the optic nerve head (ONH), eventually resulting in visual impairment and visual field loss. There are two behavioral assays that are typically used to assess visual deficits in glaucoma rodent models, the visual water task and the optokinetic drum. The visual water task can assess an animal's ability to distinguish grating patterns that are associated with an escape from water. The optokinetic drum relies on the optomotor response, a reflex turning of the head and neck in the direction of the visual stimuli, which usually consists of rotating black and white gratings. This reflex is a physiological response critical for keeping the image stable on the retina. Driven initially by the neuronal input from direction-selective RGCs, this reflex is comprised of a number of critical sensory and motor elements. In the presence of repeatable and defined stimuli, this reflex is extremely well suited to analyze subtle changes in the circuitry and performance of retinal neurons. Increasing the cycles of these alternating gratings per degree, or gradually reducing the contrast of the visual stimuli, threshold levels can be determined at which the animal is no longer tracking the stimuli, and thereby visual function of the animal can be determined non-invasively. Integrating these assays into an array of outcome measures that determine multiple aspects of visual function is a central goal in vision research and can be realized, for

  3. Anterior ischemic optic neuropathy in patients undergoing hemodialysis

    DoorenbosBot, ACC; Geerlings, W; Houtman, IA

    1996-01-01

    Four patients are discussed who underwent hemodialysis and developed anterior ischemic optic neuropathy (AION). Three patients had been treated by hemodialysis for several years. One patient developed bilateral optic neuropathy after the first hemodialysis session, So far, only four hemodialysis pat

  4. Lithium-Induced Motor Neuropathy: An Unusual Presentation

    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.

  5. Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

    de Jager, AEJ; van der Hoeven, JH

    1998-01-01

    Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually

  6. Lithium-induced motor neuropathy: An unusual presentation

    Satyakam Mohapatra; Manas Ranjan Sahoo; Neelmadhav Rath

    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.

  7. Herpes zoster motor neuropathy in a patient with previous motor paresis secondary to Vogt-Koyanagi-Harada disease.

    Sifuentes Giraldo, Walter Alberto; de la Puente Bujidos, Carlos; de Blas Beorlegui, Gema; López San Román, Antonio; Peña Arrebola, Andrés

    2013-04-01

    Motor involvement in herpes zoster is very infrequent, occurring in 3%-5% of cases, and it is caused by extension of the inflammatory process to the anterior horn motor neurons, with the subsequent development of segmental motor paralysis. The authors report a 37-yr-old woman with history of paresis in both lower limbs secondary to spinal cord atrophy associated with Vogt-Koyanagi-Harada disease and immunosuppression caused by chronic corticosteroid and azathioprine treatment of ulcerative colitis, who developed worsening of her baseline residual muscle strength in the right lower limb shortly after herpes zoster eruption. Electromyography revealed acute denervation in territories corresponding to L3-L4 and moderate widespread axonal polyneuropathy affecting both lower limbs. The patient recovered her baseline muscle strength after this event. To the best of the authors' knowledge, this is the first reported case of herpes zoster motor neuropathy in a patient with a previous motor sequel. PMID:23221673

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

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

    1996-01-01

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

  9. Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency

    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

  10. Sciatic neuropathy developed after injection during curettage.

    Altıntaş, Ayşe; Gündüz, Ayşegül; Kantarcı, Fatih; Gözübatık Çelik, Gökçen; Koçer, Naci; Kızıltan, Meral E

    2016-01-01

    Intramuscular injections are likely the most common cause of sciatic nerve injury in developing countries. Less common causes include piriformis syndrome, primary tumors of the sciatic nerve, metastatic tumors invading or compressing the nerve, endometriosis, vascular malformations, and prolonged immobilization or positioning. While the most reliable diagnostic and prognostic methods include nerve conduction studies and electromyography, magnetic resonance imaging has been suggested as an alternative method of determining type of lesion, establishing location, and investigating level of nerve involvement. A case of sciatic neuropathy that developed after intramuscular injection, with patient in prolonged lithotomy position and under sedation, is described. PMID:27225613

  11. Focal axonal swellings and associated ultrastructural changes attenuate conduction velocity in central nervous system axons: a computer modeling study.

    Kolaric, Katarina V; Thomson, Gemma; Edgar, Julia M; Brown, Angus M

    2013-08-01

    The constancy of action potential conduction in the central nervous system (CNS) relies on uniform axon diameter coupled with fidelity of the overlying myelin providing high-resistance, low capacitance insulation. Whereas the effects of demyelination on conduction have been extensively studied/modeled, equivalent studies on the repercussions for conduction of axon swelling, a common early pathological feature of (potentially reversible) axonal injury, are lacking. The recent description of experimentally acquired morphological and electrical properties of small CNS axons and oligodendrocytes prompted us to incorporate these data into a computer model, with the aim of simulating the effects of focal axon swelling on action potential conduction. A single swelling on an otherwise intact axon, as occurs in optic nerve axons of Cnp1 null mice caused a small decrease in conduction velocity. The presence of single swellings on multiple contiguous internodal regions (INR), as likely occurs in advanced disease, caused qualitatively similar results, except the dimensions of the swellings required to produce equivalent attenuation of conduction were significantly decreased. Our simulations of the consequences of metabolic insult to axons, namely, the appearance of multiple swollen regions, accompanied by perturbation of overlying myelin and increased axolemmal permeability, contained within a single INR, revealed that conduction block occurred when the dimensions of the simulated swellings were within the limits of those measured experimentally, suggesting that multiple swellings on a single axon could contribute to axonal dysfunction, and that increased axolemmal permeability is the decisive factor that promotes conduction block. PMID:24303138

  12. Early ultrastructural defects of axons and axon-glia junctions in mice lacking expression of Cnp1.

    Edgar, Julia M; McLaughlin, Mark; Werner, Hauke B; McCulloch, Mailis C; Barrie, Jennifer A; Brown, Angus; Faichney, Andrew Blyth; Snaidero, Nicolas; Nave, Klaus-Armin; Griffiths, Ian R

    2009-12-01

    Most axons in the central nervous system (CNS) are surrounded by a multilayered myelin sheath that promotes fast, saltatory conduction of electrical impulses. By insulating the axon, myelin also shields the axoplasm from the extracellular milieu. In the CNS, oligodendrocytes provide support for the long-term maintenance of myelinated axons, independent of the myelin sheath. Here, we use electron microscopy and morphometric analyses to examine the evolution of axonal and oligodendroglial changes in mice deficient in 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and in mice deficient in both CNP and proteolipid protein (PLP/DM20). We show that CNP is necessary for the formation of a normal inner tongue process of oligodendrocytes that myelinate small diameter axons. We also show that axonal degeneration in Cnp1 null mice is present very early in postnatal life. Importantly, compact myelin formed by transplanted Cnp1 null oligodendrocytes induces the same degenerative changes in shiverer axons that normally are dysmyelinated but structurally intact. Mice deficient in both CNP and PLP develop a more severe axonal phenotype than either single mutant, indicating that the two oligodendroglial proteins serve distinct functions in supporting the myelinated axon. These observations support a model in which the trophic functions of oligodendrocytes serve to offset the physical shielding of axons by myelin membranes. PMID:19459211

  13. Dynamics of axon fasciculation in the presence of neuronal turnover

    Chaudhuri, Debasish; Mohanty, P K; Zapotocky, Martin

    2008-01-01

    We formulate and characterize a model aiming to describe the formation of fascicles of axons mediated by contact axon-axon interactions. The growing axons are represented as interacting directed random walks in two spatial dimensions. To mimic axonal turnover in the mammalian olfactory system, the random walkers are injected and removed at specified rates. In the dynamical steady state, the position-dependent distribution of fascicle sizes obeys a scaling law. We identify several distinct time scales that emerge from the dynamics, are sensitive functions of the microscopic parameters of the model, and can exceed the average axonal lifetime by orders of magnitude. We discuss our findings in terms of an analytically tractable, effective model of fascicle dynamics.

  14. Axonal Protein Synthesis and the Regulation of Local Mitochondrial Function

    2009-01-01

    Axons and presynaptic nerve terminals of both invertebrate and mammalian SCG neurons contain a heterogeneous population of nuclear-encoded mitochondrial mRNAs and a local cytosolic protein synthetic system. Nearly one quarter of the total protein synthesized in these structural/functional domains of the neuron is destined for mitochondria. Acute inhibition of axonal protein synthesis markedly reduces the functional activity of mitochondria. The blockade of axonal protein into mitochondria had...

  15. Axonal protein synthesis and the regulation of local mitochondrial function

    Kaplan, B.B.; Gioio, A.E.; Hillefors, M.; Aschrafi, A.

    2009-01-01

    Axons and presynaptic nerve terminals of both invertebrate and mammalian SCG neurons contain a heterogeneous population of nuclear-encoded mitochondrial mRNAs and a local cytosolic protein synthetic system. Nearly one quarter of the total protein synthesized in these structural/functional domains of the neuron is destined for mitochondria. Acute inhibition of axonal protein synthesis markedly reduces the functional activity of mitochondria. The blockade of axonal protein into mitochondria had...

  16. Action potentials reliably invade axonal arbors of rat neocortical neurons

    Cox, Charles L.; Denk, Winfried; Tank, David W.; Svoboda, Karel

    2000-01-01

    Neocortical pyramidal neurons have extensive axonal arborizations that make thousands of synapses. Action potentials can invade these arbors and cause calcium influx that is required for neurotransmitter release and excitation of postsynaptic targets. Thus, the regulation of action potential invasion in axonal branches might shape the spread of excitation in cortical neural networks. To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon...

  17. Axon diameter mapping in crossing fibers with diffusion MRI

    Zhang, Hui; Dyrby, Tim B; Alexander, Daniel C

    2011-01-01

    tissue than measures derived from diffusion tensor imaging. Most existing techniques for axon diameter mapping assume a single axon orientation in the tissue model, which limits their application to only the most coherently oriented brain white matter, such as the corpus callosum, where the single...... technique by establishing reasonable axon diameter indices in the crossing region at the interface of the cingulum and the corpus callosum....

  18. Axon target matching in the developing visual system

    Osterhout, Jessica A.

    2015-01-01

    The central nervous system (CNS) is made up of trillions of connections between specific sets of highly specialized neurons. How each individual neuron finds and connects to the correct synaptic partner remains an important and unresolved issue in neuroscience. Using the mouse visual system as a model I probed the cellular and molecular mechanisms that govern one of the key steps leading to CNS development: axon target matching. Axon target matching is the process by which axons to find and i...

  19. Axon Regeneration in the Peripheral and Central Nervous Systems

    Huebner, Eric A.; Strittmatter, Stephen M

    2009-01-01

    Axon regeneration in the mature mammalian central nervous system (CNS) is extremely limited after injury. Consequently, functional deficits persist after spinal cord injury (SCI), traumatic brain injury, stroke, and related conditions that involve axonal disconnection. This situation differs from that in the mammalian peripheral nervous system (PNS), where long- distance axon regeneration and substantial functional recovery can occur in the adult. Both extracellular molecules and the intrinsi...

  20. Myelin sheath survival after guanethidine-induced axonal degeneration

    1992-01-01

    Membrane-membrane interactions between axons and Schwann cells are required for initial myelin formation in the peripheral nervous system. However, recent studies of double myelination in sympathetic nerve have indicated that myelin sheaths continue to exist after complete loss of axonal contact (Kidd, G. J., and J. W. Heath. 1988. J. Neurocytol. 17:245-261). This suggests that myelin maintenance may be regulated either by diffusible axonal factors or by nonaxonal mechanisms. To test these hy...

  1. Treating Painful Diabetic Peripheral Neuropathy: An Update.

    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

  2. Mitotoxicity in distal symmetrical sensory peripheral neuropathies

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

    2016-01-01

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

  3. Computer aided diagnosis of diabetic peripheral neuropathy

    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.

  4. Early diabetic neuropathy: Triggers and mechanisms

    Maxim Dobretsov; Dmitry Romanovsky; Joseph R Stimers

    2007-01-01

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

  5. Axonal autophagy during regeneration of the rat sciatic nerve

    Kangrong Lu; Zhongxian Piao; Zhenxi Liu; Weiwang Gu; Wanshan Wang; Nngjie Piao

    2008-01-01

    BACKGROUND: The removal of degenerated axonal debris during Wallerian degeneration is very important for nerve regeneration. However, the mechanism by which debris is removed is not been completely understood. Considerable controversy remains as to the clearance pathway and cells that are involved. OBJECTIVE: To investigate axonal autophagy during removal of degenerated axonal debris by transecting the sciatic nerve in a rat Wallerian degeneration model.DESIGN, TIME AND SETTING: Experimental neuropathological analysis. The experiment was conducted at the Laboratory Animal Service Center of the Southern Medical University between January and June 2005. MATERIALS: Fifty-four adult, Wistar rats of either sex, weighing 180-250 g, were obtained from the Laboratory Animal Service Center of the Southern Medical University. Animals were randomly divided into nine groups of six rats. METHODS: Wallerian degeneration was induced by transecting the rat sciatic nerve, and tissue samples from the distal stump were obtained 0.2, 0.4, 1, 2, 3, 4, 7, 10, and 15 days post-transection. Ultrathin sections were prepared for electron microscopy to study ultrastructure and enzyme cytochemistry staining. MAIN OUTCOME MEASURES: Ultrastructure (axon body, autophagic body, and cystoskeleton) of axons and myelin sheaths observed with electron microscopy; acidic phosphatase activity detected by Gomori staining using electron microscopy. RESULTS: The major changes of degenerating axons after transection were axoplasm swelling and separation of axons from their myelin sheath between five hours and two days post-transection. At four days post-transection, the axoplasm condensed and axons were completely separated from the myelin sheath, forming dissociative axon bodies. Vacuoles of different sizes formed in axons during the early phase after lesion. Larger dissociative axon bodies were formed when the axons were completely separated from the myelin sheath during a late phase. The axolemma

  6. Localization of Axonal Motor Molecules Machinery in Neurodegenerative Disorders

    Fulvio Florenzano

    2012-04-01

    Full Text Available Axonal transport and neuronal survival depend critically on active transport and axon integrity both for supplying materials and communication to different domains of the cell body. All these actions are executed through cytoskeleton, transport and regulatory elements that appear to be disrupted in neurodegenerative diseases. Motor-driven transport both supplies and clears distal cellular portions with proteins and organelles. This transport is especially relevant in projection and motor neurons, which have long axons to reach the farthest nerve endings. Thus, any disturbance of axonal transport may have severe consequences for neuronal function and survival. A growing body of literature indicates the presence of alterations to the motor molecules machinery, not only in expression levels and phosphorylation, but also in their subcellular distribution within populations of neurons, which are selectively affected in the course of neurodegenerative diseases. The implications of this altered subcellular localization and how this affects axon survival and neuronal death still remain poorly understood, although several hypotheses have been suggested. Furthermore, cytoskeleton and transport element localization can be selectively disrupted in some disorders suggesting that specific loss of the axonal functionality could be a primary hallmark of the disorder. This can lead to axon degeneration and neuronal death either directly, through the functional absence of essential axonal proteins, or indirectly, through failures in communication among different cellular domains. This review compares the localization of cytoskeleton and transport elements in some neurodegenerative disorders to ask what aspects may be essential for axon survival and neuronal death.

  7. Progression of motor axon dysfunction and ectopic Nav1.8 expression in a mouse model of Charcot-Marie-Tooth disease 1B.

    Rosberg, Mette R; Alvarez, Susana; Klein, Dennis; Nielsen, Finn Cilius; Martini, Rudolf; Levinson, S Rock; Krarup, Christian; Moldovan, Mihai

    2016-09-01

    Mice heterozygously deficient for the myelin protein P0 gene (P0+/-) develop a slowly progressing neuropathy modeling demyelinating Charcot-Marie-Tooth disease (CMT1B). The aim of the study was to investigate the long-term progression of motor dysfunction in P0+/- mice at 3, 7, 12 and 20months. By comparison with WT littermates, P0+/- showed a decreasing motor performance with age. This was associated with a progressive reduction in amplitude and increase in latency of the plantar compound muscle action potential (CMAP) evoked by stimulation of the tibial nerve at ankle. This progressive functional impairment was in contrast to the mild demyelinating neuropathy of the tibial nerve revealed by histology. "Threshold-tracking" studies showed impaired motor axon excitability in P0+/- from 3months. With time, there was a progressive reduction in threshold deviations during both depolarizing and hyperpolarizing threshold electrotonus associated with increasing resting I/V slope and increasing strength-duration time constant. These depolarizing features in excitability in P0+/- as well as the reduced CMAP amplitude were absent in P0+/- NaV1.8 knockouts, and could be acutely reversed by selective pharmacologic block of NaV1.8 in P0+/-. Mathematical modeling indicated an association of altered passive cable properties with a depolarizing shift in resting membrane potential and increase in the persistent Na(+) current in P0+/-. Our data suggest that ectopic NaV1.8 expression precipitates depolarizing conduction failure in CMT1B, and that motor axon dysfunction in demyelinating neuropathy is pharmacologically reversible. PMID:27215377

  8. Neuro-vascular-desmal relationship disturbances in peripheral nerves, dorsal root ganglions and motor segmental centers in the etoposide-induced neuropathy.

    Gerashchenko S.B.

    2007-01-01

    Full Text Available The purpose of work was to determine the mechanisms of pathologic morphogenesis of the toxic neuropathy caused by etoposide taking into consideration all complex the neuro-vascular-desmal relationship disturbances in peripheral nerves, their motor and sensor segmental centers. It has been shown in the experiments on 86 white rats that single intravenous injection of etoposide at dose of 22 mg/kg body weight induse peripheral neuropathy. The complex of morphologic methods included the neurohistological and electronic microscopic methods of the research, the histochemical markers for study transmissivity of the vessels of the circulatory bed on the light microscopic and ultrastructural levels was used. The recommendations of the Interagency Committee of Neurotoxicology were considered to choose the methods of the research. The presence of 3 stages of morphogenesis has been established - phase of primary axonal reaction (3d day of experiment, phase of disturbance of the microcirculation of peripheral nerves and their segmental centers (7th day of experiment, phase of degenerative changes (15th day. Etoposide-indused neuropathy features are determined by a singularity of interdependent reactive changes, alteration and compensation processes in sensory and motor neurons, glial cells, microcirculatory bed and connective tissue.

  9. Immediate and delayed cochlear neuropathy after noise exposure in pubescent mice.

    Jane Bjerg Jensen

    Full Text Available Moderate acoustic overexposure in adult rodents is known to cause acute loss of synapses on sensory inner hair cells (IHCs and delayed degeneration of the auditory nerve, despite the completely reversible temporary threshold shift (TTS and morphologically intact hair cells. Our objective was to determine whether a cochlear synaptopathy followed by neuropathy occurs after noise exposure in pubescence, and to define neuropathic versus non-neuropathic noise levels for pubescent mice. While exposing 6 week old CBA/CaJ mice to 8-16 kHz bandpass noise for 2 hrs, we defined 97 dB sound pressure level (SPL as the threshold for this particular type of neuropathic exposure associated with TTS, and 94 dB SPL as the highest non-neuropathic noise level associated with TTS. Exposure to 100 dB SPL caused permanent threshold shift although exposure of 16 week old mice to the same noise is reported to cause only TTS. Amplitude of wave I of the auditory brainstem response, which reflects the summed activity of the cochlear nerve, was complemented by synaptic ribbon counts in IHCs using confocal microscopy, and by stereological counts of peripheral axons and cell bodies of the cochlear nerve from 24 hours to 16 months post exposure. Mice exposed to neuropathic noise demonstrated immediate cochlear synaptopathy by 24 hours post exposure, and delayed neurodegeneration characterized by axonal retraction at 8 months, and spiral ganglion cell loss at 8-16 months post exposure. Although the damage was initially limited to the cochlear base, it progressed to also involve the cochlear apex by 8 months post exposure. Our data demonstrate a fine line between neuropathic and non-neuropathic noise levels associated with TTS in the pubescent cochlea.

  10. Focal axonal swellings and associated ultrastructural changes attenuate conduction velocity in central nervous system axons: a computer modeling study

    Kolaric, Katarina V; Thomson, Gemma; Edgar, Julia M; Brown, Angus M.

    2013-01-01

    The constancy of action potential conduction in the central nervous system (CNS) relies on uniform axon diameter coupled with fidelity of the overlying myelin providing high-resistance, low capacitance insulation. Whereas the effects of demyelination on conduction have been extensively studied/modeled, equivalent studies on the repercussions for conduction of axon swelling, a common early pathological feature of (potentially reversible) axonal injury, are lacking. The recent description of ex...

  11. Patterns of growth, axonal extension and axonal arborization of neuronal lineages in the developing Drosophila brain.

    Larsen, Camilla; Shy, Diana; Spindler, Shana R; Fung, Siaumin; Pereanu, Wayne; Younossi-Hartenstein, Amelia; Hartenstein, Volker

    2009-11-15

    The Drosophila central brain is composed of approximately 100 paired lineages, with most lineages comprising 100-150 neurons. Most lineages have a number of important characteristics in common. Typically, neurons of a lineage stay together as a coherent cluster and project their axons into a coherent bundle visible from late embryo to adult. Neurons born during the embryonic period form the primary axon tracts (PATs) that follow stereotyped pathways in the neuropile. Apoptotic cell death removes an average of 30-40% of primary neurons around the time of hatching. Secondary neurons generated during the larval period form secondary axon tracts (SATs) that typically fasciculate with their corresponding primary axon tract. SATs develop into the long fascicles that interconnect the different compartments of the adult brain. Structurally, we distinguish between three types of lineages: PD lineages, characterized by distinct, spatially separate proximal and distal arborizations; C lineages with arborizations distributed continuously along the entire length of their tract; D lineages that lack proximal arborizations. Arborizations of many lineages, in particular those of the PD type, are restricted to distinct neuropile compartments. We propose that compartments are "scaffolded" by individual lineages, or small groups thereof. Thereby, the relatively small number of primary neurons of each primary lineage set up the compartment map in the late embryo. Compartments grow during the larval period simply by an increase in arbor volume of primary neurons. Arbors of secondary neurons form within or adjacent to the larval compartments, resulting in smaller compartment subdivisions and additional, adult specific compartments. PMID:19538956

  12. The frequency of peripheral neuropathy in a group of HIV positive patients in Brazil Freqüência da neuropatia periférica no Brasil em um grupo de pacientes HIV positivo

    Claudia Zanetti

    2004-06-01

    Full Text Available Peripheral neuropathy is a common neurological complication occurring in asymptomatic and symptomatic stages of HIV infection. The most common syndromes are distal symmetric polyneuropathy, inflammatory demielinating polyneuropathy, poliradiculopathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy. PURPOSE: To evaluate the frequency of peripheral neuropathy in a group of HIV seropositive outpatients in São Paulo, Brazil. METHOD: Over a period of 17 months, 49 HIV+ patients where evaluated clinically. Laboratory analysis and electroneuromyography were requested to all patients. RESULTS: >Thirty four (69.4% of the 49 patients had the diagnosis of peripheral neuropathy established on clinical grounds. The most common sign was impairment (97.1% of sensibility. Thirteen (33.3% of the 39 that were subjected to electroneuromyography had features of peripheral neuropathy, being a sensitive-motor axonal neuropathy the most common. No abnormalities were found in the laboratory analysis performed in 42 patients, except in four who had VDRL positive. CONCLUSION: A peripheral neuropathy was frequently found upon clinical examination in our group of HIV positive individuals.A neuropatia periférica é complicação neurológica comum, podendo ocorrer nas fases assintomáticas e sintomáticas da infecção pelo vírus da imunodeficiência humana (HIV. As síndromes mais comuns são a polineuropatia distal simétrica, polineuropatia desmielinizante inflamatória, polirradiculopatia, mononeuropatia, mononeuropatia múltipla e neuropatia autonômica. OBJETIVO: Avaliar a freqüência da neuropatia periférica em um grupo de pacientes HIV positivo em São Paulo, Brasil. MÉTODO: Em um período de 17 meses, foram avaliados clinicamente 49 pacientes HIV positivos. Foram solicitados exames laboratoriais e eletroneuromiografia (ENMG para todos os pacientes. RESULTADOS: Foi estabelecido o diagnóstico clínico de neuropatia periférica em 34 (69

  13. Neurofilament gene expression: a major determinant of axonal caliber

    Within the wide spectrum of axonal diameters occurring in mammalian nerve fibers, each class of neurons has a relatively restricted range of axonal calibers. The control of caliber has functional significance because diameter is the principal determinant of conduction velocity in myelinated nerve fibers. Previous observations support the hypothesis that neurofilaments (NF) are major intrinsic determinants of axonal caliber in large myelinated nerve fibers. Following interruption of axons (axotomy) by crushing or cutting a peripheral nerve, caliber is reduced in the proximal axonal stumps, which extend from the cell bodies to the site of axotomy. This reduction in axonal caliber in the proximal stumps is associated with a selective diminution in the amount of NF protein undergoing slow axonal transport in these axons, with a decrease in axonal NF content, and with reduced conduction velocity. The present report demonstrates that changes in axonal caliber after axotomy correlate with a selective alteration in NF gene expression. Hybridization with specific cDNAs was used to measure levels of mRNA encoding the 68-kDa neurofilament protein (NF68), β-tubulin, and actin in lumbar sensory neurons of rat at various times after crushing the sciatic nerve. Between 4 and 42 days after axotomy by nerve crush, the levels of NF68 mRNA were reduced 2- to 3-fold. At the same times, the levels of tubulin and actin mRNAs were increased several-fold. These findings support the hypothesis that the expression of a single set of neuron-specific genes (encoding NF) directly determines axonal caliber, a feature neuronal morphology with important consequences for physiology and behavior

  14. Spheniodal mucocele causing bilateral optic neuropathy and ophthalmoplegia

    Ambika Selvakumar

    2014-01-01

    Full Text Available 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.

  15. Tolerability and efficacy study of P2X7 inhibition in experimental Charcot-Marie-Tooth type 1A (CMT1A) neuropathy.

    Sociali, Giovanna; Visigalli, Davide; Prukop, Thomas; Cervellini, Ilaria; Mannino, Elena; Venturi, Consuelo; Bruzzone, Santina; Sereda, Michael W; Schenone, Angelo

    2016-11-01

    Charcot-Marie-Tooth 1A (CMT1A) is a demyelinating hereditary neuropathy for which pharmacological treatments are not yet available. An abnormally high intracellular Ca(2+) concentration was observed in Schwann cells (SC) from CMT1A rats, caused by the PMP22-mediated overexpression of the P2X7 purinoceptor. The purpose of this study was to investigate the tolerability and therapeutic potential of a pharmacological antagonist of the P2X7 receptor (A438079) in CMT1A. A438079 ameliorated in vitro myelination of organotypic DRG cultures from CMT1A rats. Furthermore, we performed an experimental therapeutic trial in PMP22 transgenic and in wild-type rats. A preliminary dose-escalation trial showed that 3mg/kg A438079 administered via intraperitoneal injection every 24h for four weeks was well tolerated by wild type and CMT1A rats. Affected rats treated with 3mg/kg A438079 revealed a significant improvement of the muscle strength, when compared to placebo controls. Importantly, histologic analysis revealed a significant increase of the total number of myelinated axons in tibial nerves. Moreover, a significant decrease of the hypermyelination of small caliber axons and a significant increase of the frequency and diameter of large caliber myelinated axons was highlighted. An improved distal motor latencies was recorded, whereas compound muscle action potentials (CMAP) remained unaltered. A438079 reduced the SC differentiation defect in CMT1A rats. These results show that pharmacological inhibition of the P2X7 receptor is well tolerated in CMT1A rats and represents a proof-of-principle that antagonizing this pathway may correct the molecular derangements and improve the clinical phenotype in the CMT1A neuropathy. PMID:27431093

  16. Neuropathy-Inducing Effects of Eribulin Mesylate Versus Paclitaxel in Mice with Preexisting Neuropathy

    Wozniak, Krystyna M; Wu, Ying; Farah, Mohamed H.; Littlefield, Bruce A.; Nomoto, Kenichi; Barbara S Slusher

    2013-01-01

    Eribulin mesylate (E7389, INN:eribulin mesilate Halaven®) is a non-taxane microtubule dynamics inhibitor currently in clinical use for advanced breast cancer. Other microtubule-targeting agents for breast cancer, including paclitaxel and ixabepilone, display a common treatment dose-limiting toxicity of peripheral neuropathy (PN). In an earlier study, we found eribulin mesylate had a lower propensity to induce PN in mice than either paclitaxel or ixabepilone. In the current study, we compared ...

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

    Aristide Merola

    2016-01-01

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

  18. New insights into mRNA trafficking in axons

    Gumy, Laura; Katrukha, Eugene; Kapitein, Lukas; Hoogenraad, Casper

    2014-01-01

    In recent years, it has been demonstrated that mRNAs localize to axons of young and mature central and peripheral nervous system neurons in culture and in vivo. Increasing evidence is supporting a fundamental role for the local translation of these mRNAs in neuronal function by regulating axon growt

  19. Idebenone for Leber's hereditary optic neuropathy.

    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

  20. Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies.

    Auer-Grumbach, Michaela; Toegel, Stefan; Schabhüttl, Maria; Weinmann, Daniela; Chiari, Catharina; Bennett, David L H; Beetz, Christian; Klein, Dennis; Andersen, Peter M; Böhme, Ilka; Fink-Puches, Regina; Gonzalez, Michael; Harms, Matthew B; Motley, William; Reilly, Mary M; Renner, Wilfried; Rudnik-Schöneborn, Sabine; Schlotter-Weigel, Beate; Themistocleous, Andreas C; Weishaupt, Jochen H; Ludolph, Albert C; Wieland, Thomas; Tao, Feifei; Abreu, Lisa; Windhager, Reinhard; Zitzelsberger, Manuela; Strom, Tim M; Walther, Thomas; Scherer, Steven S; Züchner, Stephan; Martini, Rudolf; Senderek, Jan

    2016-09-01

    Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade β-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment. PMID:27588448

  1. Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease

    Laurent P. Bogdanik

    2013-05-01

    Charcot-Marie-Tooth disease (CMT is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P. Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.

  2. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons.

    Bei, Fengfeng; Lee, Henry Hing Cheong; Liu, Xuefeng; Gunner, Georgia; Jin, Hai; Ma, Long; Wang, Chen; Hou, Lijun; Hensch, Takao K; Frank, Eric; Sanes, Joshua R; Chen, Chinfei; Fagiolini, Michela; He, Zhigang

    2016-01-14

    Although a number of repair strategies have been shown to promote axon outgrowth following neuronal injury in the mammalian CNS, it remains unclear whether regenerated axons establish functional synapses and support behavior. Here, in both juvenile and adult mice, we show that either PTEN and SOCS3 co-deletion, or co-overexpression of osteopontin (OPN)/insulin-like growth factor 1 (IGF1)/ciliary neurotrophic factor (CNTF), induces regrowth of retinal axons and formation of functional synapses in the superior colliculus (SC) but not significant recovery of visual function. Further analyses suggest that regenerated axons fail to conduct action potentials from the eye to the SC due to lack of myelination. Consistent with this idea, administration of voltage-gated potassium channel blockers restores conduction and results in increased visual acuity. Thus, enhancing both regeneration and conduction effectively improves function after retinal axon injury. PMID:26771493

  3. Receptor Tyrosine Kinases: Molecular Switches Regulating CNS Axon Regeneration

    Vasanthy Vigneswara

    2012-01-01

    Full Text Available The poor or lack of injured adult central nervous system (CNS axon regeneration results in devastating consequences and poor functional recovery. The interplay between the intrinsic and extrinsic factors contributes to robust inhibition of axon regeneration of injured CNS neurons. The insufficient or lack of trophic support for injured neurons is considered as one of the major obstacles contributing to their failure to survive and regrow their axons after injury. In the CNS, many of the signalling pathways associated with neuronal survival and axon regeneration are regulated by several classes of receptor tyrosine kinases (RTK that respond to a variety of ligands. This paper highlights and summarises the most relevant recent findings pertinent to different classes of the RTK family of molecules, with a particular focus on elucidating their role in CNS axon regeneration.

  4. SnoN facilitates axonal regeneration after spinal cord injury.

    Jiun L Do

    Full Text Available Adult CNS neurons exhibit a reduced capacity for growth compared to developing neurons, due in part to downregulation of growth-associated genes as development is completed. We tested the hypothesis that SnoN, an embryonically regulated transcription factor that specifies growth of the axonal compartment, can enhance growth in injured adult neurons. In vitro, SnoN overexpression in dissociated adult DRG neuronal cultures significantly enhanced neurite outgrowth. Moreover, TGF-β1, a negative regulator of SnoN, inhibited neurite outgrowth, and SnoN over-expression overcame this inhibition. We then examined whether SnoN influenced axonal regeneration in vivo: indeed, expression of a mutant form of SnoN resistant to degradation significantly enhanced axonal regeneration following cervical spinal cord injury, despite peri-lesional upregulation of TGF-β1. Thus, a developmental mechanism that specifies extension of the axonal compartment also promotes axonal regeneration after adult CNS injury.

  5. Effects of Lipoic Acid on Acrylamide Induced Testicular Damage

    Lebda, Mohamed; Gad, Shereen; Gaafar, Hossam

    2014-01-01

    Introduction: Acrylamide is very toxic to various organs and associated with significant increase of oxidative stress and depletion of antioxidants. Alpha-lipoic acid enhances cellular antioxidant defense capacity, thereby protecting cells from oxidative stress. Aim of the study: This study aimed to evaluate the protective role of alpha-lipoic acid on the oxidative damage induced by acrylamide in testicular and epididymal tissues. Material and methods: Forty adult male rats were divided into ...

  6. Modulation Of Acrylamide-Induced Biochemical Alterations In Albino Rats

    Acrylamide (ACR) is an industrial neurotoxic chemical that has been recently found in carbohydrate rich foods cooked at high temperature. The objective of the current study is to evaluate the protective effects of rosemary extract against ACR-induced toxicity in rats. The experimental rats were divided into four groups included a control group, a group treated orally with rosemary extract by supercritical fluid extractor (150 mg/kg/day) for 14 days, a group treated orally with ACR (50 mg/kg/day) for 14 days and a group treated orally with rosemary extract + acrylamide for 14 days. The results indicated that treatment with ACR alone resulted in a significant decrease in the haematological parameters, triglycerides, insulin, creatine kinase and choline esterase while the concentrations of urea, creatinine, ALT, AST and alkaline phosphatase were increased. Treatment with rosemary extract during ACR treatment reduced the effects induced by ACR. It could be concluded that rosemary extract exhibited a protective action against ACR-induced biochemical alterations in rats. For this reason, rosemary is recommended to be used in cooked food due to its palatable taste and prophylactic effect.

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

    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

  8. A case report of congenital sensory neuropathy with anhidrosis

    Congenital sensory neuropathy with anhidrosis is rare disease and may be confused with other cause of pain insensitivity or indifference. Other cause of pain insensitivity include congenital indifference to pain, congenital sensory neuropathy, hereditary sensory radicular neuropathy, nonprogressive sensory radicular neuropathy, syringomyelia, and hysterical analgesia. It is hereditary disease which is transmitted with autosomal recessive trait. The patient is 8 years old Korean male with complaint of swelling and local heat on right knee joint. Generalized analgesia is noted on physical examination. The skin is dry and coarse with no evidence of sweating. Delayed motor development was noted on early children. Mental development is retarded. On past history, patient showed unpredictable rises of temperature, though the general condition remained good. Multiple painless fracture on right humerus and right metatasal bone was occurred. Rt.knee radiograms show marked swelling of soft tissue and periosteal calcification on distal femru,which are resemble with neurotrophic joint

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

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

    2016-01-01

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

  10. Hepatitis C virus infection, cryoglobulinemia, and peripheral neuropathy: a case report

    Vigani A.G.

    2005-01-01

    Full Text Available Hepatitis C virus (HCV is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy, cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week and ribavirin (500 mg orally, twice a day for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.

  11. Brain injury tolerance limit based on computation of axonal strain.

    Sahoo, Debasis; Deck, Caroline; Willinger, Rémy

    2016-07-01

    Traumatic brain injury (TBI) is the leading cause of death and permanent impairment over the last decades. In both the severe and mild TBIs, diffuse axonal injury (DAI) is the most common pathology and leads to axonal degeneration. Computation of axonal strain by using finite element head model in numerical simulation can enlighten the DAI mechanism and help to establish advanced head injury criteria. The main objective of this study is to develop a brain injury criterion based on computation of axonal strain. To achieve the objective a state-of-the-art finite element head model with enhanced brain and skull material laws, was used for numerical computation of real world head trauma. The implementation of new medical imaging data such as, fractional anisotropy and axonal fiber orientation from Diffusion Tensor Imaging (DTI) of 12 healthy patients into the finite element brain model was performed to improve the brain constitutive material law with more efficient heterogeneous anisotropic visco hyper-elastic material law. The brain behavior has been validated in terms of brain deformation against Hardy et al. (2001), Hardy et al. (2007), and in terms of brain pressure against Nahum et al. (1977) and Trosseille et al. (1992) experiments. Verification of model stability has been conducted as well. Further, 109 well-documented TBI cases were simulated and axonal strain computed to derive brain injury tolerance curve. Based on an in-depth statistical analysis of different intra-cerebral parameters (brain axonal strain rate, axonal strain, first principal strain, Von Mises strain, first principal stress, Von Mises stress, CSDM (0.10), CSDM (0.15) and CSDM (0.25)), it was shown that axonal strain was the most appropriate candidate parameter to predict DAI. The proposed brain injury tolerance limit for a 50% risk of DAI has been established at 14.65% of axonal strain. This study provides a key step for a realistic novel injury metric for DAI. PMID:27038501

  12. Nutritional optic and peripheral neuropathy: a case report

    Nightingale, Laura M; Paviour, Dominic C.

    2009-01-01

    Introduction The link between nutritional status and either optic or peripheral neuropathies is well established with tobacco, ethanol, deficiencies in thiamine, vitamin A, B12, B3 and B6 and protein-energy malnutrition all being causative. Case presentation We describe the case of a 32-year-old Afro-Caribbean of Jamaican origin presenting with blurred vision and a painful burning sensation in his feet. The clinical features were consistent with optic and peripheral neuropathy. Conclusions Th...

  13. Ischaemic optic neuropathy with painful ophthalmoplegia in diabetes mellitus.

    Jabs, D A; Miller, N. R.; Green, W R

    1981-01-01

    Two patients with mild, adult-onset diabetes mellitus developed a painful ophthalmoplegia and ipsilateral optic neuropathy that was relatively unresponsive to steroids. Histopathological study of the optic nerve of one patient revealed an extensive ischaemic infarct. There was ultimate recovery from the cranial nerve palsies in both patients and the optic neuropathy in one patient. Ischaemic polyneuropathy involving the cranial nerves may cause an orbital apex/cavernous sinus syndrome in pati...

  14. Therapeutische Überlegungen bei sensomotorischer diabetischer Neuropathie

    Bührlen M

    2013-01-01

    Der Begriff der sensomotorischen diabetischen Neuropathie beschreibt einen heterogenen Beschwerdekomplex, der auf einer diabetesbedingten Schädigung des peripheren Nervensystems beruht. Bis zu 50 % der Menschen mit Diabetes mellitus leiden im Verlauf ihrer Erkrankung an Symptomen einer sensomotorischen Neuropathie. Chronische Schmerzen, Dysund Parästhesien sowie die Komplikation des diabetischen Fußsyndroms stellen für die Betroffenen gravierende Folgen dar. Die Optimierung der met...

  15. The clinical spectrum of inflammatory-angiopathic neuropathy.

    Harati, Y; Niakan, E

    1986-01-01

    Thirty-three patients with inflammatory-angiopathic neuropathy diagnosed by sural nerve biopsy, were investigated to determine the underlying disease. Twenty-six patients had symmetrical sensorimotor polyneuropathy and seven had mononeuropathy multiplex. An aetiology for inflammatory-angiopathic neuropathy was found in only eight patients: typical collagen vascular disease in five and malignant tumour in three. Sixteen patients received prednisone and/or immunosuppressive drug therapy and 12 ...

  16. The pathological basis of conduction block in human neuropathies.

    Feasby, T E; Brown, W F; Gilbert, J J; Hahn, A F

    1985-01-01

    Conduction block was detected in patients with neuropathy by measuring a decrease in the size of the compound muscle action potential of more than 20% on proximal versus distal stimulation of the peroneal, median or ulnar nerve in the absence of excess temporal dispersion of the potential. The teased fibre analyses of nerve biopsies from four patients with "definite" and six patients with "probable" conduction block and from seven patients with neuropathy but without conduction block were com...

  17. An unusual case of suprascapular nerve neuropathy: a case report

    Kyriakides Theodoros; Christodoulou Loizos; Economides Charalambos P; Soteriades Elpidoforos S

    2011-01-01

    Abstract Introduction Suprascapular nerve neuropathy constitutes an unusual cause of shoulder weakness, with the most common etiology being nerve compression from a ganglion cyst at the suprascapular or spinoglenoid notch. We present a puzzling case of a man with suprascapular nerve neuropathy that may have been associated with an appendectomy. The case was attributed to nerve injury as the most likely cause that may have occurred during improper post-operative patient mobilization. Case pres...

  18. Subclinical Ulnar Neuropathy at the Elbow in Diabetic Patients

    Jang, Ji Eun; Kim, Yun Tae; Park, Byung Kyu; Cheong, In Yae; Kim, Dong Hwee

    2014-01-01

    Objective To demonstrate the prevalence and characteristics of subclinical ulnar neuropathy at the elbow in diabetic patients. Methods One hundred and five patients with diabetes mellitus were recruited for the study of ulnar nerve conduction analysis. Clinical and demographic characteristics were assessed. Electrodiagnosis of ulnar neuropathy at the elbow was based on the criteria of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM1 and AANEM2). The inching test ...

  19. Oxidative Injury and Neuropathy in Diabetes and Impaired Glucose Tolerance

    Russell, James W.; Berent-Spillson, Alison; Vincent, Andrea M.; Freimann, Catherine L.; Sullivan, Kelli A; Eva L Feldman

    2008-01-01

    Clinical studies suggest that impaired glucose tolerance (IGT) is associated with the development of neuropathy. The aim of the current study was to determine if neuropathy developed in the female Zucker Diabetic Fatty (ZDF) rat, an animal model of IGT and type 2 diabetes. The ZDF rat develops impaired glucose tolerance (IGT) when fed a control diet, and frank diabetes when fed a high fat diet. Following 10 weeks of hyperglycemia, sensory nerve action potentials (SNAP) and compound motor acti...

  20. HIV peripheral neuropathy progression: protection with glucose-lowering drugs?

    Evans, Scott R.; Lee, Anthony J.; Ellis, Ronald J.; Chen, Huichao; Wu, Kunling; Bosch, Ronald J.; Clifford, David B.

    2012-01-01

    The purpose of this study is to evaluate risk factors for progression from asymptomatic peripheral neuropathy (APN) to symptomatic peripheral neuropathy (SPN). Antiretroviral therapy (ART)-naïve patients initiating combination ART were followed longitudinally and screened for signs/ symptoms of PN. Having APN was associated with higher odds of future SPN (odds ratio (OR)=1.58, 95 % confidence interval (CI)=(1.08, 2.29), p=0.027). Neurotoxic ART use was associated with increased odds of progre...

  1. Reversal of dysthyroid optic neuropathy following orbital fat decompression

    Kazim, M; Trokel, S; Acaroglu, G; Elliott, A

    2000-01-01

    AIMS—To document the successful treatment of five patients with dysthyroid optic neuropathy by orbital fat decompression instead of orbital bone decompression after failed medical therapy.
METHODS—Eight orbits of five patients with dysthyroid optic neuropathy were selected for orbital fat decompression as an alternative to bone removal decompression. Treatment with systemic corticosteroids and/or orbital radiotherapy was either unsuccessful or contraindicated in each case. All patients satisf...

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

    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%) develope...

  3. Neuropathie bei Patienten mit Diabetes mellitus in Tansania

    Michaelsen, Jens Kersten

    2011-01-01

    Ziel der Studie ist es Daten bezüglich Eigenschaften, Stoffwechseleinstellung, den Prävalenzen von Neuropathien und Komplikationen bei Patienten mit Diabetes mellitus in Tansania zu sammeln. Im Kilimanjaro Christian Medical Centre werden 96 - Typ 1 und Typ 2 - Diabetiker im Alter von 13 bis 95 Jahren untersucht. Der HbA1c- Wert wird gemessen und anhand des Neuropathy Symptome Score (NSS) und Neuropathy Deficit Score (NDS) der Neuropathiegrad bestimmt. Ergebnis: Die mittlere Diabete...

  4. Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

    Kannan, Anusha; Srinivasan, Sivasubramanian [Khoo Teck Puat Hospital, Singapore (Singapore)

    2012-09-15

    We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.

  5. 4S RNA is transported axonally in normal and regenerating axons of the sciatic nerves of rats

    Experiments were designed to determine if following injection of [3H]uridine into the lumbar spinal cord of the rat, [3H]RNA could be demonstrated within axons of the sciatic nerve, and if 4S RNA is the predominant predominant RNA species present in these axons. (Auth.)

  6. Diagnosing ulnar neuropathy at the elbow using magnetic resonance neurography

    Keen, Nayela N.; Chin, Cynthia T.; Saloner, David; Steinbach, Lynne S. [University of California San Francisco, Dept of Radiology and Biomedical Imaging, San Francisco, CA (United States); Engstrom, John W. [University of California San Francisco, Department of Neurology, San Francisco, CA (United States)

    2012-04-15

    Early diagnosis of ulnar neuropathy at the elbow is important. Magnetic resonance neurography (MRN) images peripheral nerves. We evaluated the usefulness of elbow MRN in diagnosing ulnar neuropathy at the elbow. The MR neurograms of 21 patients with ulnar neuropathy were reviewed retrospectively. MRN was performed prospectively on 10 normal volunteers. The MR neurograms included axial T1 and axial T2 fat-saturated and/or axial STIR sequences. The sensitivity and specificity of MRN in detecting ulnar neuropathy were determined. The mean ulnar nerve size in the symptomatic and normal groups was 0.12 and 0.06 cm{sup 2} (P < 0.001). The mean relative signal intensity in the symptomatic and normal groups was 2.7 and 1.4 (P < 0.01). When using a size of 0.08 cm{sup 2}, sensitivity was 95% and specificity was 80%. Ulnar nerve size and signal intensity were greater in patients with ulnar neuropathy. MRN is a useful test in evaluating ulnar neuropathy at the elbow. (orig.)

  7. Potential risk factors for diabetic neuropathy: a case control study

    Nooraei Mahdi

    2005-12-01

    Full Text Available Abstract Background Diabetes mellitus type II afflicts at least 2 million people in Iran. Neuropathy is one of the most common complications of diabetes and lowers the patient's quality of life. Since neuropathy often leads to ulceration and amputation, we have tried to elucidate the factors that can affect its progression. Methods In this case-control study, 110 diabetic patients were selected from the Shariati Hospital diabetes clinic. Michigan Neuropathic Diabetic Scoring (MNDS was used to differentiate cases from controls. The diagnosis of neuropathy was confirmed by nerve conduction studies (nerve conduction velocity and electromyography. The multiple factors compared between the two groups included consumption of angiotensin converting enzyme inhibitors (ACEI, blood pressure, serum lipid level, sex, smoking, method of diabetes control and its quality. Results Statistically significant relationships were found between neuropathy and age, gender, quality of diabetes control and duration of disease (P values in the order: 0.04, 0.04, Conclusion In this study, hyperglycemia was the only modifiable risk factor for diabetic neuropathy. Glycemic control reduces the incidence of neuropathy, slows its progression and improves the diabetic patient's quality of life. More attention must be paid to elderly male diabetic patients with poor diabetes control with regard to regular foot examinations and more practical education.

  8. Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons

    Balaštík, Martin; Zhou, X.Z.; Alberich-Jorda, Meritxell; Weissová, Romana; Žiak, Jakub; Pazyra-Murphy, M.F.; Cosker, K.E.; Machoňová, Olga; Kozmiková, Iryna; Chen, CH.; Pastorino, L.; Asara, J.M.; Cole, A.; Sutherland, C.; Segal, R. A.; Lu, K.P.

    2015-01-01

    Roč. 13, č. 4 (2015), s. 812-828. ISSN 2211-1247 R&D Projects: GA MŠk(CZ) LK11213; GA MŠk LK21307; GA ČR GA15-03796S; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : Pin1 * axon guidance * Semaphorin 3A Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.358, year: 2014

  9. Clinical features of diffuse axonal injury

    2001-01-01

    Objective: To analyze the mechanism of diffuse axonal injury (DAI) and study the relationship between DAI and brain concussion, brain contusion, and primary brain stem injury.Methods: The clinical data and iconographic characteristics of 56 patients with DAI were analyzed retrospectively.Results: Traffic accidents were the main cause of DAI. Among the 56 cases, 34 were injured for at least twice, and 71.43% of the patients were complicated with contusion.Conclusions: It is considered that DAI is a common pattern of primary brain injury, which is often underestimated. And DAI includes cerebral concussion and primary brain injury, and is often complicated by cerebral cortex contusion. Therefore, it is very simple and practical to divide primary brain injuries into local and diffuse injuries.

  10. Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene.

    Sanmaneechai, Oranee; Feely, Shawna; Scherer, Steven S; Herrmann, David N; Burns, Joshua; Muntoni, Francesco; Li, Jun; Siskind, Carly E; Day, John W; Laura, Matilde; Sumner, Charlotte J; Lloyd, Thomas E; Ramchandren, Sindhu; Shy, Rosemary R; Grider, Tiffany; Bacon, Chelsea; Finkel, Richard S; Yum, Sabrina W; Moroni, Isabella; Piscosquito, Giuseppe; Pareyson, Davide; Reilly, Mary M; Shy, Michael E

    2015-11-01

    We aimed to characterize genotype-phenotype correlations and establish baseline clinical data for peripheral neuropathies caused by mutations in the myelin protein zero (MPZ) gene. MPZ mutations are the second leading cause of Charcot-Marie-Tooth disease type 1. Recent research makes clinical trials for patients with MPZ mutations a realistic possibility. However, the clinical severity varies with different mutations and natural history data on progression is sparse. We present cross-sectional data to begin to define the phenotypic spectrum and clinical baseline of patients with these mutations. A cohort of patients with MPZ gene mutations was identified in 13 centres of the Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC-RDCRC) between 2009 and 2012 and at Wayne State University between 1996 and 2009. Patient phenotypes were quantified by the Charcot-Marie-Tooth disease neuropathy score version 1 or 2 and the Charcot-Marie-Tooth disease paediatric scale outcome instruments. Genetic testing was performed in all patients and/or in first- or second-degree relatives to document mutation in MPZ gene indicating diagnosis of Charcot-Marie-Tooth disease type 1B. There were 103 patients from 71 families with 47 different MPZ mutations with a mean age of 40 years (range 3-84 years). Patients and mutations were separated into infantile, childhood and adult-onset groups. The infantile onset group had higher Charcot-Marie-Tooth disease neuropathy score version 1 or 2 and slower nerve conductions than the other groups, and severity increased with age. Twenty-three patients had no family history of Charcot-Marie-Tooth disease. Sixty-one patients wore foot/ankle orthoses, 19 required walking assistance or support, and 10 required wheelchairs. There was hearing loss in 21 and scoliosis in 17. Forty-two patients did not begin walking until after 15 months of age. Half of the infantile onset patients then required ambulation aids or wheelchairs for

  11. Membrane turnover and receptor trafficking in regenerating axons.

    Hausott, Barbara; Klimaschewski, Lars

    2016-02-01

    Peripheral axonal regeneration requires surface-expanding membrane addition. The continuous incorporation of new membranes into the axolemma allows the pushing force of elongating microtubules to drive axonal growth cones forwards. Hence, a constant supply of membranes and cytoskeletal building blocks is required, often for many weeks. In human peripheral nerves, axonal tips may be more than 1 m away from the neuronal cell body. Therefore, in the initial phase of regeneration, membranes are derived from pre-existing vesicles or synthesised locally. Only later stages of axonal regeneration are supported by membranes and proteins synthesised in neuronal cell bodies, considering that the fastest anterograde transport mechanisms deliver cargo at 20 cm/day. Whereas endocytosis and exocytosis of membrane vesicles are balanced in intact axons, membrane incorporation exceeds membrane retrieval during regeneration to compensate for the loss of membranes distal to the lesion site. Physiological membrane turnover rates will not be established before the completion of target reinnervation. In this review, the current knowledge on membrane traffic in axonal outgrowth is summarised, with a focus on endosomal vesicles as the providers of membranes and carriers of growth factor receptors required for initiating signalling pathways to promote the elongation and branching of regenerating axons in lesioned peripheral nerves. PMID:26222895

  12. Astrocyte scar formation aids central nervous system axon regeneration.

    Anderson, Mark A; Burda, Joshua E; Ren, Yilong; Ao, Yan; O'Shea, Timothy M; Kawaguchi, Riki; Coppola, Giovanni; Khakh, Baljit S; Deming, Timothy J; Sofroniew, Michael V

    2016-04-14

    Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration. PMID:27027288

  13. Intra-axonal myosin and actin in nerve regeneration.

    McQuarrie, Irvine G; Lund, Linda M

    2009-10-01

    A focused review of sciatic nerve regeneration in the rat model, based on research conducted by the authors, is presented. We examine structural proteins carried distally in the axon by energy-requiring motor enzymes, using protein chemistry and molecular biology techniques in combination with immunohistochemistry. Relevant findings from other laboratories are cited and discussed. The general conclusion is that relatively large amounts of actin and tubulin are required to construct a regenerating axon and that these materials mainly originate in the parent axon. The motor enzymes that carry these proteins forward as macromolecules include kinesin and dynein but probably also include myosin. PMID:19927086

  14. Axon guidance and neuronal migration research in China

    2010-01-01

    Proper migration of neuronal somas and axonal growth cones to designated locations in the developing brain is essential for the assembly of functional neuronal circuits.Rapid progress in research of axon guidance and neuronal migration has been made in the last twenty years.Chinese researchers began their exploration in this field ten years ago and have made significant contributions in clarifying the signal transduction of axon guidance and neuronal migration.Several unique experimental approaches,including the migration assay of single isolated neurons in response to locally delivered guidance cues,have been developed by Chinese neuroscientists to investigate the molecular machinery underlying these guidance events.

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

    Saidha, Shiv

    2010-04-19

    Abstract Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4%) had neuropathies remote from procedural sites and 36 patients (54.5%) had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15\\/30) developed following relatively short procedures. In 27% of cases (8\\/30) remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7\\/30: 23.3%), making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12\\/36, 33.3%) accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF) formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation.

  16. Frequency of sensory motor neuropathy in type 2 diabetics

    To determine the frequency of sensory motor neuropathy in type 2 diabetics at the time of presentation to the hospital. The study was conducted at Medical Unit-1, Jinnah Postgraduate Medical Center, Karachi, from November 2005 to April 2006. Patients of different ages and either gender with history of confirmed diabetes for ten years and above, on regular follow up were included. Those with non-diabetic causes of hyperglycemia or neuropathy were excluded. Relevant features like age, gender, treatment, symptoms , signs, nerve conduction study (NCS) results, duration of Diabetes mellitus (DM), fasting blood sugar (FBS) and serum values of glycosylated hemoglobin (HB1Ac) were recorded. Out of a total of 300 patients, there were 111 female and 189 male patients. Mean age was 58 +- 11.23 years. Mean duration of diabetes was 13.6+-5.48 years. One hundred and twenty three patients had symptoms of neuropathy. Clinical examination revealed mixed sensory and motor signs in 135 (45%) patients. Nerve conduction studies revealed abnormalities in 159 (53%) patients. Among patients having an abnormal NCS, the fasting blood glucose (FBS) was 120mg/dl in 147 (91%) patients. The glycosylated hemoglobin ranged from 4-15% with mean of 8.1% and standard deviation of 2.5%. This showed significant association (p <0.001) of peripheral neuropathy with abnormal FBS, HB1Ac and duration of diabetes. NCS diagnosed the neuropathy in more than half of the total number of patients, including both symptomatic and asymptomatic patients. Majority of the patients revealed symmetrical and a mixed type (motor and sensory) polyneuropathy. This shows that nerve conduction may not be concordant with the clinical signs and symptoms. NCS detects neuropathy much earlier, before it becomes evident clinically. The neuropathy is associated with abonromal fasting blood sugar, HBIAC and duration of diabetes. (author)

  17. Painful Diabetic Neuropathy: Prevention or Suppression?

    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

  18. CURRENT THERAPEUTIC STRATEGY IN DIABETIC NEUROPATHY

    Kaur Parminder

    2012-03-01

    Full Text Available Diabetic neuropathy (DN is a group of multifactorial disorder in diabetic patients, which affects neuronal function of the whole body and is accompanied by nephropathy and angiopathy. Its prevalence increases with duration of diabetes and hyperglycaemia which can induce oxidative stress resulting in activation of multiple pathways which can damage the neurons alone or in combination. Symptoms of DN are prominent early in type 2 than in type 1. Neuropathic pain which can occur continuously only in 20-30% of the patients, otherwise pain was not reported. The drugs available for DN were not able to cure the disease but provide only symptomatic relief and were also associated with major side effects. Current therapy provided in this review alleviates the symptoms in clinical trials and thus will be recommended in order to stop the progression of disease. Despite the recent understanding regarding the pathogenesis of disease, till date only two drugs were approved by FDA for DN, α-lipoic acid is available in several countries and epalrestat in Japan, which is also associated with side effects but they are tolerable.

  19. Traumatic Optic Neuropathy – A Conundrum

    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.

  20. Diabetic neuropathy and plasma glucose control.

    Porte, D; Graf, R J; Halter, J B; Pfeifer, M A; Halar, E

    1981-01-01

    Diabetic neuropathy is defined, and theories of its pathogenesis are reviewed. Recent studies designed to investigate the influence of plasma glucose on nerve function in noninsulin-dependent diabetic patients are summarized. Motor nerve conduction velocities in the median and peroneal nerves were measured using a double-stimulus technique, and sensory conduction velocity was measured by conventional methods before and after therapy with oral agents or insulin. The degree of hyperglycemia was assessed by measurement of fasting plasma glucose and glycosylated hemoglobin concentrations. The degree of slowing in motor nerve conduction velocity in untreated patients was found to correlate with the fasting plasma glucose and glycosylated hemoglobin concentrations, but sensory nerve function, although abnormal, did not show such correlation. Reduction of hyperglycemia was associated with improvement in motor nerve conduction velocity in the peroneal and median motor nerves of these patients, but sensory nerve conduction velocity showed no such improvement. Improvement in median motor nerve conduction velocity was directly related to the degree of reduction in fasting plasma glucose concentration. These findings suggest that metabolic factors related to hyperglycemia are important in the impaired motor nerve function seen in noninsulin-dependent patients with maturity-onset diabetes. PMID:7457487

  1. Toxic optic neuropathy: An unusual cause

    Hema L Ramkumar

    2014-01-01

    Full Text Available A 60-year-old woman with a history of chronic alcoholism and tobacco use presented with the complaint of a painless decrease in vision in both eyes. She lost vision first in the left eye then in the right eye. She admitted consuming at least one 16 ounce bottle of over the counter mouthwash daily and denied consumption of any other alcohols, methanol, or antifreeze. She stated that her vision had been continuing to deteriorate in both eyes. Her best-corrected visual acuity was 4/200 in each eye. Color vision was nil in each eye. Her pupils were sluggish bilaterally, and her optic discs were flat and hyperemic with peripapillary hemorrhages. Her visual fields revealed central scotomas bilaterally. The magnetic resonance imaging of the brain and lumbar puncture were within normal limits. Antinuclear antibody, human leukocyte antigen-B27 genotyping, and B12 were normal; serum thiamine was low. While continuing to ingest mouthwash, her vision decreased to count fingers at 2 feet, and maculopapillary bundle pallor developed. She was started on folate and thiamine supplementation. Once she discontinued mouthwash, her vision improved to 20/400 bilaterally, and her central scotomas improved. This case demonstrates an alcohol-induced toxic optic neuropathy from mouthwash ingestion with some visual recovery after discontinuation of the offending agent.

  2. Phenotypic variability of TRPV4 related neuropathies

    Evangelista, Teresinha; Bansagi, Boglarka; Pyle, Angela; Griffin, Helen; Douroudis, Konstantinos; Polvikoski, Tuomo; Antoniadi, Thalia; Bushby, Kate; Straub, Volker; Chinnery, Patrick F.; Lochmüller, Hanns; Horvath, Rita

    2015-01-01

    Mutations in the transient receptor potential vanilloid 4 (TRPV4) gene have been associated with autosomal dominant skeletal dysplasias and peripheral nervous system syndromes (PNSS). PNSS include Charcot–Marie–Tooth disease (CMT) type 2C, congenital spinal muscular atrophy and arthrogryposis and scapuloperoneal spinal muscular atrophy. We report the clinical, electrophysiological and muscle biopsy findings in two unrelated patients with two novel heterozygous missense mutations in the TRPV4 gene. Whole exome sequencing was carried out on genomic DNA using Illumina TruseqTM 62Mb exome capture. Patient 1 harbours a de novo c.805C > T (p.Arg269Cys) mutation. Clinically, this patient shows signs of both scapuloperoneal spinal muscular atrophy and skeletal dysplasia. Patient 2 harbours a novel c.184G > A (p.Asp62Asn) mutation. While the clinical phenotype is compatible with CMT type 2C with the patient's muscle harbours basophilic inclusions. Mutations in the TRPV4 gene have a broad phenotypic variability and disease severity and may share a similar pathogenic mechanism with Heat Shock Protein related neuropathies. PMID:25900305

  3. Strategies and Methods for the Treatment of Diabetic Neuropathy Using Integrative Chinese and Western Medicine

    HENG Xian-pei

    2008-01-01

    @@ Diabetic neuropathy (DN) is the most common metabolic neuropathy in clinics, not only in diabetes patients (>60%), but also in pre-diabetic (8%) and normal persons (5%)(1). Its pathogenesis has not been fully understood up to now.

  4. Internodal function in normal and regenerated mammalian axons

    Moldovan, M; Krarup, C

    2007-01-01

    AIM: Following Wallerian degeneration, peripheral myelinated axons have the ability to regenerate and, given a proper pathway, establish functional connections with targets. In spite of this capacity, the clinical outcome of nerve regeneration remains unsatisfactory. Early studies have found that...

  5. Syndecan Promotes Axon Regeneration by Stabilizing Growth Cone Migration

    Tyson J. Edwards

    2014-07-01

    Full Text Available Growth cones facilitate the repair of nervous system damage by providing the driving force for axon regeneration. Using single-neuron laser axotomy and in vivo time-lapse imaging, we show that syndecan, a heparan sulfate (HS proteoglycan, is required for growth cone function during axon regeneration in C. elegans. In the absence of syndecan, regenerating growth cones form but are unstable and collapse, decreasing the effective growth rate and impeding regrowth to target cells. We provide evidence that syndecan has two distinct functions during axon regeneration: (1 a canonical function in axon guidance that requires expression outside the nervous system and depends on HS chains and (2 an intrinsic function in growth cone stabilization that is mediated by the syndecan core protein, independently of HS. Thus, syndecan is a regulator of a critical choke point in nervous system repair.

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

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

    2016-05-01

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

  7. Treadmill Training Promotes Axon Regeneration in Injured Peripheral Nerves

    Sabatier, Manning J.; Redmon, Natalie; Schwartz, Gail; English, Arthur W.

    2008-01-01

    Physical activity after spinal cord injury promotes improvements in motor function, but its effects following peripheral nerve injury are less clear. Although axons in peripheral nerves are known to regenerate better than those in the CNS, methods of accelerating regeneration are needed due to the slow overall rate of growth. Therefore we studied the effect of two weeks of treadmill locomotion on the growth of regenerating axons in peripheral nerves following injury. The common fibular nerves...

  8. Modality-Specific Axonal Regeneration: Towards selective regenerative neural interfaces

    Mario I Romero

    2011-10-01

    Full Text Available Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, sensory and motor axons at the neural interface are of mixed submodality types, which difficult the specific recording from motor axons and the eliciting of precise sensory modalities through selective stimulation. Here we evaluated the possibility of using type-specific neurotrophins to preferentially entice the regeneration of defined axonal populations from transected peripheral nerves into separate compartments. Segregation of mixed sensory fibers from dorsal root ganglion neurons was evaluated in vitro by compartmentalized diffusion delivery of nerve growth factor (NGF and neurotrophin-3 (NT-3, to preferentially entice the growth of TrkA+ nociceptive and TrkC+ proprioceptive subsets of sensory neurons, respectively. The average axon length in the NGF channel increased 2.5 fold compared to that in saline or NT-3, whereas the number of branches increased 3 fold in the NT-3 channels. These results were confirmed using a 3-D “Y”-shaped in vitro assay showing that the arm containing NGF was able to entice a 5-fold increase in axonal length of unbranched fibers. To address if such segregation can be enticed in vivo, a “Y”-shaped tubing was used to allow regeneration of the transected adult rat sciatic nerve into separate compartments filled with either NFG or NT-3. A significant increase in the number of CGRP+ pain fibers were attracted towards the sural nerve, while N-52+ large diameter axons were observed in the tibial and NT-3 compartments. This study demonstrates the guided enrichment of sensory axons in specific regenerative chambers, and supports the notion that neurotrophic factors can be used to segregate sensory and perhaps motor axons in separate peripheral interfaces.

  9. Axonal integrity predicts cortical reorganisation following cervical injury

    Freund, P.; Wheeler-Kingshott, C.A.; Nagy, Z.; Gorgoraptis, N.; N. Weiskopf; Friston, K.; Thompson, A J; Hutton, C.

    2012-01-01

    Background Traumatic spinal cord injury (SCI) leads to disruption of axonal architecture and macroscopic tissue loss with impaired information flow between the brain and spinal cord—the presumed basis of ensuing clinical impairment. Objective The authors used a clinically viable, multimodal MRI protocol to quantify the axonal integrity of the cranial corticospinal tract (CST) and to establish how microstructural white matter changes in the CST are related to cross-sectional spinal cord area a...

  10. Changes in prefrontal axons may disrupt the network in autism

    Zikopoulos, Basilis; Barbas, Helen

    2010-01-01

    Neural communication is disrupted in autism by unknown mechanisms. Here we examined whether in autism there are changes in axons, which are the conduit for neural communication. We investigated single axons and their ultrastructure in the white matter of post-mortem human brain tissue below the anterior cingulate cortex (ACC), orbitofrontal (OFC), and lateral (LPFC) prefrontal cortices, which are associated with attention, social interactions, and emotions and have been consistently implicate...

  11. Axonal maintenance, glia, exosomes, and heat shock proteins

    Michael Tytell; Lasek, Raymond J.; Harold Gainer

    2016-01-01

    Of all cellular specializations, the axon is especially distinctive because it is a narrow cylinder of specialized cytoplasm called axoplasm with a length that may be orders of magnitude greater than the diameter of the cell body from which it originates. Thus, the volume of axoplasm can be much greater than the cytoplasm in the cell body. This fact raises a logistical problem with regard to axonal maintenance. Many of the components of axoplasm, such as soluble proteins and cytoskeleton, are...

  12. The effects of Capillary Dysfunction on Oxygen and Glucose extraction in Diabetic Neuropathy

    Østergaard, Leif; Finnerup, Nanna Brix; Terkelsen, Astrid J.; Aamand, Rasmus; Drasbek, Kim Ryun; Knudsen, Lone; Jespersen, Sune Nørhøj; Frystyk, Jan; Charles, Morten; Thomsen, Reimar W.; Christiansen, Jens Sandahl; Beck-Nielsen, Henning; Jensen, Troels Staehelin; Andersen, Henning

    2015-01-01

    development of diabetic neuropathy in humans, and in manifest neuropathy, reductions in nerve conduction velocity correlate with the level of endoneurial hypoxia. The idea that microvascular changes cause diabetic neuropathy is contradicted, however, by reports of elevated endoneurial blood flow in early...... neuropathy, and whether the observed relation between endoneurial blood flow and nerve function is consistent with increasingly disturbed capillary flow patterns. The analysis suggests testable relations between capillary dysfunction, tissue hypoxia, aldose reductase activity, oxidative stress, tissue...

  13. Focal and multifocal diabetic neuropathies Neuropatia diabética focal e multifocal

    Gérard Said

    2007-01-01

    Diabetic neuropathy is the most common neuropathy in industrialized countries, with a remarkable range of clinical manifestations. The vast majority of the patients with clinical diabetic neuropathy have a distal symmetrical form that progress following a fiber-length dependent pattern, with predominant sensory and autonomic manifestations. This pattern of neuropathy is associated with a progressive distal axonopathy. Patients are exposed to trophic changes in the feet, pains and autonomic di...

  14. THEORETICAL PRINCIPLES UNDERLYING OPTICAL STIMULATION OF MYELINATED AXONS EXPRESSING CHANNELRHODOPSIN-2

    ARLOW, R. L.; FOUTZ, T. J.; MCINTYRE, C. C.

    2013-01-01

    Numerous clinical conditions can be treated by neuromodulation of the peripheral nervous system (PNS). Typical electrical PNS therapies activate large diameter axons at lower electrical stimulus thresholds than small diameter axons. However, recent animal experiments with peripheral optogenetic neural stimulation (PONS) of myelinated axons expressing channelrhodopsin-2 (ChR2) have shown that this technique activates small diameter axons at lower irradiances than large diameter axons. We hypot...

  15. Spinal irradiation does not inhibit distal axonal sprouting

    In an attempt to determine the relative importance of the nerve cell body and of the axon in initiating and controlling axonal regeneration, nerve cell bodies were irradiated and the ability of the distal axon to sprout was examined. Mice were subjected to either 25 or 50 Gray (Gy) of x-irradiation localized to the lumbar spinal cord. After times varying from 1 day to 6 months after irradiation, a sublethal dose of botulinum toxin (BoTx) was injected into the calf muscles of one leg. The soleus muscle was examined histologically after times varying from 1 week to 6 months after injection, and BoTx-induced ultraterminal axonal sprouting was assessed by the number of motor endplates showing sprouts, the length of the sprouts, and the long term endplate morphology. Apart from some irradiated subgroups having slightly shorter sprout lengths, no significant differences were found between irradiated and nonirradiated groups. The results suggest either that the processes in the nerve cell body responsible for initiating and supporting axonal growth are resistant to large doses of irradiation, or that growth regulatory mechanisms in the distal axon are under local control

  16. Dynamics of signal propagation and collision in axons

    Follmann, Rosangela; Rosa, Epaminondas; Stein, Wolfgang

    2015-09-01

    Long-range communication in the nervous system is usually carried out with the propagation of action potentials along the axon of nerve cells. While typically thought of as being unidirectional, it is not uncommon for axonal propagation of action potentials to happen in both directions. This is the case because action potentials can be initiated at multiple "ectopic" positions along the axon. Two ectopic action potentials generated at distinct sites, and traveling toward each other, will collide. As neuronal information is encoded in the frequency of action potentials, action potential collision and annihilation may affect the way in which neuronal information is received, processed, and transmitted. We investigate action potential propagation and collision using an axonal multicompartment model based on the Hodgkin-Huxley equations. We characterize propagation speed, refractory period, excitability, and action potential collision for slow (type I) and fast (type II) axons. In addition, our studies include experimental measurements of action potential propagation in axons of two biological systems. Both computational and experimental results unequivocally indicate that colliding action potentials do not pass each other; they are reciprocally annihilated.

  17. Axon-glia interaction and membrane traffic in myelin formation

    Robin eWhite

    2014-01-01

    Full Text Available In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialised glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarisation followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasising the central role of the Src-family kinase Fyn during CNS myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of PLP (proteolipid protein transport by SNARE proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  18. The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy

    Hansen, C. S.; Jensen, T.M.; Jensen, J S;

    2015-01-01

    peripheral neuropathy was assessed by vibration detection threshold (n = 319), 10 g monofilament (n = 543) and the Michigan Neuropathy Screening Instrument questionnaire (n = 966). Painful diabetic neuropathy was assessed using the Brief Pain Inventory short form (n = 882). RESULTS: No associations between...

  19. [Acro-osteolysis with hereditary sensory ulcero-mutilating neuropathy. Apropos of an atypical case].

    Carabelli, A; Ruggeri, R; Pessina, R; Cerri, D; Bertani, E

    1989-01-01

    The authors report an acroosteolysis case with sensory radicular ulcero-mutilating neuropathy. The differential diagnosis are discussed and the case is presented as an intermediate form between the congenital sensory neuropathy, type II, according to Otha classification, and the non-progressive, sporadical sensory neuropathy. PMID:2638645

  20. Ultrastructural observation of effect of moderate hypothermia on axonal damage in an animal model of diffuse axonal injury

    孙晓川; 唐文渊; 郑履平

    2002-01-01

    Objective: To investigate the effect of moderate hypothermia on responses of axonal cytoskeleton to axonal injury in the acute stage of injury. Methods: Of fifteen adult guinea pigs, twelve animals were subjected to stretch injury to the right optic nerves and divided into the normothermic group (n=6) in which the animal's core temperature was maintained at 36.0-37.5℃ and the hypothermia group (n=6) in which the core temperature was reduced to 32.0-32.5℃ after stretch injury. Remaining three animals sustained no injury to the right optic nerves and served as control group. Half of injured animals (n=3) of either normothermic group or hypothermic group were killed at either 2 hours or 4 hours after injury. The ultrastructural changes of axonal cytoskeleton of the right optic nerve fibers from the animals were examined under a transmission electron microscope and analyzed by quantitative analysis with a computer image analysis system. Results: At 2 hours after stretch injury, there was a significant reduction in the mean number of microtubules (P<0.001), and a significant increase in the mean intermicrotubule spacing (P<0.05 or P<0.01) in axons of all sizes in normothermic animals. The mean number of neurofilaments also decreased statistically (P<0.01) in large and medium subgroups of axons in the same experimental group at 2 hours. By 4 hours, the large subgroup of axons in normothermic animals still demonstrated a significant decline in the mean number of microtubules (P<0.01) and an increase in the mean intermicrotubule spacing (P<0.05), while the medium and small subgroups of axons displayed a significant increase in the mean number of neurofilaments (P<0.05) and reduction in the mean interneurofilament spacing (P<0.05). On the contrary, either the mean number of microtubules and the mean intermicrotubule spacing, or the mean number of neurofilaments and interneurofilament spacing in axons of all sizes in hypothermic stretch-injured animals was not

  1. UTILITY OF F WAVE MINIMAL LATENCY FOR DIAGNOSIS OF DIABETIC NEUROPATHY

    Gargate

    2014-12-01

    Full Text Available BACKGROUND: Diabetes mellitus (DM is a metabolic disorder which has become a major public health problem worldwide. Its commonest complication is diabetic peripheral neuropathy (DPN. DPN is characterized by combining axonal loss and demyelinating sensory motor peripheral neuropathy. To investigate this condition nerve conduction studies with determination of latency and velocity are commonly used as they are considered to be the most sensitive, reliable, non-invasive and objective means. DPN is believed to affect mainly distal nerve segments. However, it has been recently reported that F-wave study in diabetic patients is very reliable. AIM: Aim of the present study was to find out whether F-wave minimal latency (FWML is having more sensitivity compared to motor nerve conduction study for diagnosis of DPN. METHODS AND MATERIALS: Motor and sensory nerve conduction and F-wave studies of upper and lower extremity nerves were carried out bilaterally in 60 clinically diagnosed patients with Type II diabetes mellitus. These parameters were also studied in 45 age matched controls. RESULTS: Sensitivity for distal motor latency (DML was 53.33% in median, 26.31% in ulnar, 25.8% in peroneal and 41.17% in tibial nerves. Sensitivity for motor amplitude- compound muscle action potential (CMAP was 56.66% in the median, 66.66% in ulnar, 80.64% in personnel and 72.54% in tibial nerves. Sensitivity for motor conduction velocity (MNCV was 50% in the median, 47.36% in ulnar, 77.41% in personnel and 72.55% in tibial nerves. Sensitivity for distal sensory latency (DSL was 37.97% in the median, 23.8% in ulnar, 41.5% in sural nerves. Sensitivity for sensory amplitude (SNAP was 8.01% in the median, 64.28% in ulnar and 60.37% in sural nerves. Sensitivity for sensory conduction velocity (SNCV was 40.5% in median, 26.19% in ulnar and 58.49% in Sural nerves. Prolonged FWMLs were found in 73.87% of median, 69% of ulnar, 72.72% of peroneal and 68.96% of tibial nerves. The

  2. Symmetrical Femoral Neuropathy and Rhabdomyolysis Complicating Carbon Monoxide Poisoning

    Shih-Hua Kuo

    2006-08-01

    Full Text Available Although carbon monoxide (CO is a common cause of morbidity due to poisoning,peripheral neuropathy following CO poisoning has rarely been reported. Furthermore, rhabdomyolysiscaused of CO poisoning is also uncommon. The report focuses on a patient withsymmetrical femoral neuropathy and rhabdomyolysis associated with CO poisoning.A 32-year-old male was admitted to hospital in a deep coma following CO poisoning.On admission, rhabdomylosis was also identified (total creatinine phosphokinase, 19662IU/L; CK-MB, 272 IU/L. After receiving hyperbaric oxygen, the patient regained consciousness;however, bilateral hip flexors and knee extensors were still weak in accordanceto the manual muscle test. Lumbar spine magnetic resonance imaging (MRI was performedand did not reveal any abnormal lesions. Nerve conduction examination and electromyographyresults indicated symmetrical femoral neuropathy. After taking the rehabilitation programfor peripheral and central nervous system lesions, the patient achieved functionalimprovement in ambulation, endurance and balance.

  3. Antiretroviral therapy-induced Leber’s hereditary optic neuropathy

    Anand Moodley

    2014-05-01

    Full Text Available Optic neuropathy in HIV-infected patients results from the HIV infection itself, post-infectious auto-immune disease, opportunistic infections and drugs. Nucleoside reverse transcriptase inhibitors (NRTIs such as zidovudine and stavudine have known mitochondrial toxicity and can cause mitochondrial myopathies, neuropathies, hyperlactataemia, and can induce mitochondrial genetic disorders. Individuals with the mutation for Leber’s hereditary optic neuropathy (LHON, a mitochondrial disorder, are usually asymptomatic but develop visual loss when exposed to external triggers such as smoking. We report on two HIV-infected patients with LHON mutations (m.14484T>C and m.11778G>A who developed profound visual loss with antiretroviral therapy. We postulate that the phenotypic expression of LHON in these genetically predisposed individuals was triggered by NRTI drugs lamivudine and tenofovir when used in combination, despite their relatively weak mitochondrial toxic effects. 

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

    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

  5. HIV-related neuropathy: current perspectives

    Schütz SG

    2013-09-01

    Full Text Available Sonja G Schütz, Jessica Robinson-Papp Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA Abstract: Distal symmetric polyneuropathy (DSP related to human immunodeficiency virus (HIV is one of the most common neurologic complications of HIV, possibly affecting as many as 50% of all individuals infected with HIV. Two potentially neurotoxic mechanisms have been proposed to play a crucial role in the pathogenesis of HIV DSP: neurotoxicity resulting from the virus and its products; as well as adverse neurotoxic effects of medications used in the treatment of HIV. Clinically, HIV DSP is characterized by a combination of signs and symptoms that include decreased deep tendon reflexes at the ankles and decreased sensation in the distal extremities as well as paresthesias, dysesthesias, and pain in a symmetric stocking–glove distribution. These symptoms are generally static or slowly progressive over time, and depending on the severity, may interfere significantly with the patient's daily activities. In addition to the clinical picture, nerve conduction studies and skin biopsies are often pursued to support the diagnosis of HIV DSP. Anticonvulsants, antidepressants, topical agents, and nonspecific analgesics may help relieve neuropathic pain. Specifically, gabapentin, lamotrigine, pregabalin, amitriptyline, duloxetine, and high-dose topical capsaicin patches have been used in research and clinical practice. Further research is needed to elucidate the pathogenesis of HIV DSP, thus facilitating the development of novel treatment strategies. This review discusses the epidemiology, pathophysiology, clinical findings, diagnosis, and management of DSP in the setting of HIV. Keywords: neuropathy, human immunodeficiency virus, acquired immunodeficiency syndrome, AIDS, distal symmetric polyneuropathy, DSP, pain

  6. Regeneration of motor axons in the rat sciatic nerve studied by labeling with axonally transported radioactive proteins

    Labeling regenerating axons with axonally transported radioactive proteins provides information about the location of the entire range of axons from the fastest growing ones to those which are trapped in the scar. This technique has been used to study the regeneration of motor axons in the rat sciatic nerve after a crush lesion. From 2 to 14 days after the crush the lumbar spinal cord was exposed by laminectomy and multiple injections of [3H]proline were made stereotactically in the ventral horn. Twenty-four hours later the nerves were removed and the distribution of radioactivity along the nerve was measured by liquid scintillation counting. There was a peak of radioactivity in the regenerating axons distal to the crush due to an accumulation of label in the tips of these axons. After a delay of 3.2 +- 0.2 (S.E.) days, this peak advanced down the nerve at a rate of 3.0 +- 0.1 (S.E.) mm/day. The leading edge of this peak, which marks the location of the endings of the most rapidly growing labeled fibers, moved down the nerve at a rate of 4.4 +- 0.2 mm/day after a delay of 2.1 +- 0.2 days; this is the same time course as that of the most rapidly regenerating sensory axons in the rat sciatic nerve, measured by the pinch test. Another peak of radioactivity at the crush site, presumed to represent the ends of unregenerated axons or misdirected sprouts, declined rapidly during the first week, and more slowly thereafter. (Auth.)

  7. Nonarteritic ischemic optic neuropathy developed after capsular block syndrome

    Volkan Hurmeric

    2014-01-01

    Full Text Available A 65-year-old man developed capsular block syndrome in the early postoperative period, following phacoemulsification surgery. After neodymium-doped yttrium aluminum garnet (Nd:YAG laser anterior capsulotomy, the intraocular pressure remained elevated for 4 days despite antiglaucomatous medication. On the postoperative fifth day, nonarteritic ischemic optic neuropathy was diagnosed. To the best of our knowledge, this is the first report of a case with nonarteritic ischemic optic neuropathy associated with early postoperative capsular block syndrome after phacoemulsification surgery.

  8. Multiple Crush Concept Applied to Multiple Nerves in Leprous Neuropathy.

    Dellon, A Lee

    2016-04-01

    There is a large reservoir of leprosy patients, no longer contagious, due to multidrug therapy, who are considered cured and are becoming increasingly disabled due to progressive chronic nerve entrapment in the upper and lower extremities. After a review of the history of understanding leprous neuropathy, an approach is outlined based on the approach taken to relieve pain and restore sensation that prevents ulcers and amputations in diabetics with neuropathy and superimposed nerve compressions. The results of the first application of this approach in an indigenous area for leprosy, Guayaquil, Ecuador, is discussed with implications for international care of this neglected patient population. PMID:27013412

  9. Four cases of radiation retinopathy and optic neuropathy

    We observed retinopathy and optic neuropathy in 4 patients after radiation for malignancies in the paranasal sinus or the brain. The dosis ranged from 56 Gy for 14 days to 64 Gy for 32 days. The interval between the termination of radiation and onset of fundus lesions ranged from 1 to 36 months, average 16.6 months. The retinopathy appeared as retinal hemorrhage, soft exudates and vitreous hemorrhage. Neovascular glaucoma developed in one eye. The optic neuropathy appeared as pallor of optic disc, disc edema or optic papillitis. Histological studies of one eye with retinopathy showed thickening of retinal capillary walls and rubeosis iridis with angle closure. (author)

  10. Axonal synapses utilize multiple synaptic ribbons in the mammalian retina.

    Hong-Lim Kim

    Full Text Available In the mammalian retina, bipolar cells and ganglion cells which stratify in sublamina a of the inner plexiform layer (IPL show OFF responses to light stimuli while those that stratify in sublamina b show ON responses. This functional relationship between anatomy and physiology is a key principle of retinal organization. However, there are at least three types of retinal neurons, including intrinsically photosensitive retinal ganglion cells (ipRGCs and dopaminergic amacrine cells, which violate this principle. These cell types have light-driven ON responses, but their dendrites mainly stratify in sublamina a of the IPL, the OFF sublayer. Recent anatomical studies suggested that certain ON cone bipolar cells make axonal or ectopic synapses as they descend through sublamina a, thus providing ON input to cells which stratify in the OFF sublayer. Using immunoelectron microscopy with 3-dimensional reconstruction, we have identified axonal synapses of ON cone bipolar cells in the rabbit retina. Ten calbindin ON cone bipolar axons made en passant ribbon synapses onto amacrine or ganglion dendrites in sublamina a of the IPL. Compared to the ribbon synapses made by bipolar terminals, these axonal ribbon synapses were characterized by a broad postsynaptic element that appeared as a monad and by the presence of multiple short synaptic ribbons. These findings confirm that certain ON cone bipolar cells can provide ON input to amacrine and ganglion cells whose dendrites stratify in the OFF sublayer via axonal synapses. The monadic synapse with multiple ribbons may be a diagnostic feature of the ON cone bipolar axonal synapse in sublamina a. The presence of multiple ribbons and a broad postsynaptic density suggest these structures may be very efficient synapses. We also identified axonal inputs to ipRGCs with the architecture described above.

  11. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  12. In vivo imaging of axonal transport using MRI: aging and Alzheimer's disease

    MRI using manganese as a trans-synaptic axonal tracing agent can unveil dynamics of axonal transport in living subjects. We use this technology to test the hypotheses if impaired axonal transport is a significant pathophysiological process in aging and early Alzheimer's disease (AD) and in part accounting for ''selective vulnerability'' of projection neurons in AD. To allow quantitative assessment of axonal transport in vivo, we developed voxel-based statistical mapping technology as well as a tracer kinetic modeling method based on mass transport for manganese-enhanced MRI to estimate axonal transport rates in aging rats and AD transgenic mice. These techniques demonstrated manganese-enhanced signal changes in axonal projections of the olfactory tract and decreased axonal transport rates in rodent models of aging and AD. Altered axonal transport may be a critical pathophysiological process in aging and AD. Manganese-enhanced MRI provides exciting opportunities for the investigations of altered axonal transport in AD and related disorders. (orig.)

  13. Regulation of Microtubule Dynamics in Axon Regeneration: Insights from C. elegans [version 1; referees: 3 approved

    Ngang Heok Tang

    2016-04-01

    Full Text Available The capacity of an axon to regenerate is regulated by its external environment and by cell-intrinsic factors. Studies in a variety of organisms suggest that alterations in axonal microtubule (MT dynamics have potent effects on axon regeneration. We review recent findings on the regulation of MT dynamics during axon regeneration, focusing on the nematode Caenorhabditis elegans. In C. elegans the dual leucine zipper kinase (DLK promotes axon regeneration, whereas the exchange factor for Arf6 (EFA-6 inhibits axon regeneration. Both DLK and EFA-6 respond to injury and control axon regeneration in part via MT dynamics. How the DLK and EFA-6 pathways are related is a topic of active investigation, as is the mechanism by which EFA-6 responds to axonal injury. We evaluate potential candidates, such as the MT affinity-regulating kinase PAR-1/MARK, in regulation of EFA-6 and axonal MT dynamics in regeneration.

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

    Lee, D.A. [Univ. Medical Center, New Orleans, LA (United States); Gross, L.; Wittrock, D.A.; Windebank, A.J. [Mayo Clinic, Rochester, MN (United States)

    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.

  15. Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy

    Bountra Chas

    2007-05-01

    Full Text Available Abstract Background Transient receptor potential (TRP receptors expressed by primary sensory neurons mediate thermosensitivity, and may play a role in sensory pathophysiology. We previously reported that human dorsal root ganglion (DRG sensory neurons co-expressed TRPV1 and TRPV3, and that these were increased in injured human DRG. Related receptors TRPV4, activated by warmth and eicosanoids, and TRPM8, activated by cool and menthol, have been characterised in pre-clinical models. However, the role of TRPs in common clinical sensory neuropathies needs to be established. Methods We have studied TRPV1, TRPV3, TRPV4, and TRPM8 in nerves (n = 14 and skin from patients with nerve injury, avulsed dorsal root ganglia (DRG (n = 11, injured spinal nerve roots (n = 9, diabetic neuropathy skin (n = 8, non-diabetic neuropathic nerve biopsies (n = 6, their respective control tissues, and human post mortem spinal cord, using immunohistological methods. Results TRPV1 and TRPV3 were significantly increased in injured brachial plexus nerves, and TRPV1 in hypersensitive skin after nerve repair, whilst TRPV4 was unchanged. TRPM8 was detected in a few medium diameter DRG neurons, and was unchanged in DRG after avulsion injury, but was reduced in axons and myelin in injured nerves. In diabetic neuropathy skin, TRPV1 expressing sub- and intra-epidermal fibres were decreased, as was expression in surviving fibres. TRPV1 was also decreased in non-diabetic neuropathic nerves. Immunoreactivity for TRPV3 was detected in basal keratinocytes, with a significant decrease of TRPV3 in diabetic skin. TRPV1-immunoreactive nerves were present in injured dorsal spinal roots and dorsal horn of control spinal cord, but not in ventral roots, while TRPV3 and TRPV4 were detected in spinal cord motor neurons. Conclusion The accumulation of TRPV1 and TRPV3 in peripheral nerves after injury, in spared axons, matches our previously reported changes in avulsed DRG. Reduction of TRPV1 levels

  16. Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

    Mélodie Aubart

    Full Text Available BACKGROUND: Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined. METHODS: All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases. RESULTS: Thirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects. Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2 disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients. INTERPRETATION: SMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II

  17. Metabolite profile of a mouse model of Charcot–Marie–Tooth type 2D neuropathy: implications for disease mechanisms and interventions

    Bais, Preeti; Beebe, Kirk; Morelli, Kathryn H.; Currie, Meagan E.; Norberg, Sara N.; Evsikov, Alexei V.; Miers, Kathy E.; Seburn, Kevin L.; Guergueltcheva, Velina; Kremensky, Ivo; Jordanova, Albena; Bult, Carol J.

    2016-01-01

    ABSTRACT Charcot–Marie–Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot–Marie–Tooth type 2D neuropathy (CMT2D) is caused by dominant mutations in glycyl tRNA synthetase (GARS). Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D. How mutations in GARS lead to peripheral neuropathy remains controversial. To identify putative disease mechanisms, we compared metabolites isolated from the spinal cord of Gars mutant mice and their littermate controls. A profile of altered metabolites that distinguish the affected and unaffected tissue was determined. Ascorbic acid was decreased fourfold in the spinal cord of CMT2D mice, but was not altered in serum. Carnitine and its derivatives were also significantly reduced in spinal cord tissue of mutant mice, whereas glycine was elevated. Dietary supplementation with acetyl-L-carnitine improved gross motor performance of CMT2D mice, but neither acetyl-L-carnitine nor glycine supplementation altered the parameters directly assessing neuropathy. Other metabolite changes suggestive of liver and kidney dysfunction in the CMT2D mice were validated using clinical blood chemistry. These effects were not secondary to the neuromuscular phenotype, as determined by comparison with another, genetically unrelated mouse strain with similar neuromuscular dysfunction. However, these changes do not seem to be causative or consistent metabolites of CMT2D, because they were not observed in a second mouse Gars allele or in serum samples from CMT2D patients. Therefore, the metabolite ‘fingerprint’ we have identified for CMT2D improves our understanding of cellular biochemical changes associated with GARS mutations, but identification of efficacious treatment strategies and elucidation of the disease mechanism will require additional studies. PMID:27288508

  18. Functional complexity of the axonal growth cone: a proteomic analysis.

    Adriana Estrada-Bernal

    Full Text Available The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥ 99% confidence level. Using informatics, including functional annotation cluster and KEGG pathway analysis, we found great diversity of proteins involved in axonal pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate metabolism, as expected. We also found a large and complex array of proteins involved in translation, protein folding, posttranslational processing, and proteasome/ubiquitination-dependent degradation. Immunofluorescence studies performed on hippocampal neurons in culture confirmed the presence in the axonal growth cone of proteins representative of these processes. These analyses also provide evidence for rough endoplasmic reticulum and reveal a reticular structure equipped with Golgi-like functions in the axonal growth cone. Furthermore, Western blot revealed the growth cone enrichment, relative to fetal brain homogenate, of some of the proteins involved in protein synthesis, folding and catabolism. Our study provides a resource for further research and amplifies the relatively recently developed concept that the axonal growth cone is equipped with proteins capable of performing a highly diverse range of functions.

  19. A novel technique using hydrophilic polymers to promote axonal fusion

    Ravinder Bamba; D Colton Riley; Nathaniel D Kelm; Mark D Does; Richard D Dortch; Wesley P hTayer

    2016-01-01

    The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.e., Wallerian degeneration) has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration (~1 mm/day). When axons are severed, the endings undergo calcium-mediated plasmalemmal sealing, which limits the ability of the axon to be primarily re-paired. Polythethylene glycol (PEG) in combination with a bioengineered process overcomes the inability to fuse axons. The mechanism for PEG axonal fusion is not clearly understood, but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion. The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur. This review highlights PEG fusion, its past and current studies, and future directions in PEG fusion.

  20. Highly effective photonic cue for repulsive axonal guidance.

    Bryan J Black

    Full Text Available In vivo nerve repair requires not only the ability to regenerate damaged axons, but most importantly, the ability to guide developing or regenerating axons along paths that will result in functional connections. Furthermore, basic studies in neuroscience and neuro-electronic interface design require the ability to construct in vitro neural circuitry. Both these applications require the development of a noninvasive, highly effective tool for axonal growth-cone guidance. To date, a myriad of technologies have been introduced based on chemical, electrical, mechanical, and hybrid approaches (such as electro-chemical, optofluidic flow and photo-chemical methods. These methods are either lacking in desired spatial and temporal selectivity or require the introduction of invasive external factors. Within the last fifteen years however, several attractive guidance cues have been developed using purely light based cues to achieve axonal guidance. Here, we report a novel, purely optical repulsive guidance technique that uses low power, near infrared light, and demonstrates the guidance of primary goldfish retinal ganglion cell axons through turns of up to 120 degrees and over distances of ∼90 µm.

  1. Subtypes of GABAergic neurons project axons in the neocortex

    Shigeyoshi Higo

    2009-11-01

    Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

  2. Spinal MRI of vincristine neuropathy mimicking Guillain-Barre syndrome

    A 4.3-year-old girl with acute leukaemia, who was being treated with chemotherapy (including vincristine), developed paraplegia. Spinal MRI showed diffusely enhancing nerve roots on contrast-enhanced images. Spinal fluid analysis showed a normal protein level. Vincristine neuropathy mimicking Guillain-Barre syndrome is thought to be the cause of the MRI abnormalities. (orig.)

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

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

    2016-04-26

    Inherited demyelinating peripheral neuropathies are progressive incurable diseases without effective treatment. To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we delivered a lentiviral vector using a single lumbar intrathecal injection and a myelin-specific promoter. The human gene of interest, GJB1, which is mutated in X-linked Charcot-Marie-Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1-null mice, a genetically authentic model of CMT1X that develops a demyelinating peripheral neuropathy. We obtained widespread, stable, and cell-specific expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal roots and peripheral nerves. Behavioral and electrophysiological analysis revealed significantly improved motor performance, quadriceps muscle contractility, and sciatic nerve conduction velocities. Furthermore, treated mice exhibited reduced numbers of demyelinated and remyelinated fibers and fewer inflammatory cells in lumbar motor roots, as well as in the femoral motor and sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene delivery can lead to Schwann cell-specific expression in spinal roots extending to multiple peripheral nerves. This clinically relevant approach improves the phenotype of an inherited neuropathy mouse model and provides proof of principle for treating inherited demyelinating neuropathies. PMID:27035961

  4. Genetics Home Reference: hereditary sensory and autonomic neuropathy type IE

    ... of the neurons that make up the nervous system. However, it is not known how the mutations cause the specific signs and symptoms of HSAN IE. Learn more about the gene associated with hereditary sensory and autonomic neuropathy type IE DNMT1 Related Information ...

  5. Prevalence of diabetic autonomic neuropathy measured by simple bedside tests

    Dyrberg, Torben Bech; Benn, Jette; Christiansen, J S;

    1981-01-01

    To investigate the prevalence of diabetic autonomic neuropathy, five simple bedside tests, beat-to-beat variation during quiet respiration, beat-to-beat variation during forced respiration, heart rate and blood pressure response to standing, heart rate response to exercise, and heart rate respons...

  6. PERIPHERAL NEUROPATHY ELECTROPHYSIOLOGICAL SCREENING IN CHILDREN WITH CELIAC DISEASE

    Şedat IŞIKAY

    2015-06-01

    Full Text Available Background The involvement of the peripheral nervous system in children with celiac disease is particularly rare. Objective The aim of this study was to assess the need for neurophysiological testing in celiac disease patients without neurological symptoms in order to detect early subclinical neuropathy and its possible correlations with clinical and demographic characteristics. Methods Two hundred and twenty consecutive children with celiac disease were screened for neurological symptoms and signs, and those without symptoms or signs were included. Also, patients with comorbidities associated with peripheral neuropathy or a history of neurological disease were excluded. The remaining 167 asymptomatic patients as well as 100 control cases were tested electro-physiologically for peripheral nervous system diseases. Motor nerve conduction studies, including F-waves, were performed for the median, ulnar, peroneal, and tibial nerves, and sensory nerve conduction studies were performed for the median, ulnar, and sural nerves with H reflex of the soleus muscle unilaterally. All studies were carried out using surface recording electrodes. Normative values established in our laboratory were used. Results Evidence for subclinical neuropathy was not determined with electrophysiological studies in any of the participants. Conclusion In this highly selective celiac disease group without any signs, symptoms as well as the predisposing factors for polyneuropathy, we did not determine any cases with neuropathy. With these results we can conclude that in asymptomatic cases with celiac disease electrophysiological studies are not necessary. However, larger studies with the electrophysiological studies performed at different stages of disease at follow-ups are warranted.

  7. Reappraising entrapment neuropathies--mechanisms, diagnosis and management.

    Schmid, Annina B; Nee, Robert J; Coppieters, Michel W

    2013-12-01

    The diagnosis of entrapment neuropathies can be difficult because symptoms and signs often do not follow textbook descriptions and vary significantly between patients with the same diagnosis. Signs and symptoms which spread outside of the innervation territory of the affected nerve or nerve root are common. This Masterclass provides insight into relevant mechanisms that may account for this extraterritorial spread in patients with entrapment neuropathies, with an emphasis on neuroinflammation at the level of the dorsal root ganglia and spinal cord, as well as changes in subcortical and cortical regions. Furthermore, we describe how clinical tests and technical investigations may identify these mechanisms if interpreted in the context of gain or loss of function. The management of neuropathies also remains challenging. Common treatment strategies such as joint mobilisation, neurodynamic exercises, education, and medications are discussed in terms of their potential to influence certain mechanisms at the site of nerve injury or in the central nervous system. The mechanism-oriented approach for this Masterclass seems warranted given the limitations in the current evidence for the diagnosis and management of entrapment neuropathies. PMID:24008054

  8. Spinal MRI of vincristine neuropathy mimicking Guillain-Barre syndrome

    Chang, Yun Woo; Yoon, Hye-Kyung; Cho, Jae Min [Department of Radiology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710 (Korea); Sung, Ki Woong [Department of Paediatrics, Samsung Medical Centre, Seoul 135-710 (Korea)

    2003-11-01

    A 4.3-year-old girl with acute leukaemia, who was being treated with chemotherapy (including vincristine), developed paraplegia. Spinal MRI showed diffusely enhancing nerve roots on contrast-enhanced images. Spinal fluid analysis showed a normal protein level. Vincristine neuropathy mimicking Guillain-Barre syndrome is thought to be the cause of the MRI abnormalities. (orig.)

  9. Mixed connective tissue disease presenting as trigeminal neuropathy

    Edmondstone, W M; Price, D. K.; Shepherd, T. H.; Gooddy, W. W.

    1982-01-01

    A 25-year-old man presented with an isolated trigeminal neuropathy 13 months before developing myalgia and lymphadenopathy. The onset of Raynaud's phenomenon 2 months later suggested a diagnosis of mixed connective tissue disease (MCTD) and this was confirmed by high serum titres of speckled pattern antinuclear antibody, and antibody to ribonuclear protein.

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

    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

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

    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]), su

  12. Neurolysis and myocutaneous flap for radiation induced brachial plexus neuropathy

    Surgical treatment for radiation induced brachial plexus neuropathy is difficult. We followed 9 patients of radiation induced brachial plexus neuropathy who were surgically treated with neurolysis and myocutaneous flap coverage. Their ages ranged from 29 to 72 years old. Their diagnoses were breast cancer in 6 patients, lingual cancer in 1, thyroid cancer in 1 and malignant lymphoma in 1. Total dose of radiation ranged from 44 to 240 Gy. Interval from radiation therapy to our surgery ranged from 1 to 18 years (mean 6.7 years). Chief complaints were dysesthesia in 9 patients, motor weakness in 7 patients and dullach in scar formation of radiated skin in 7 patients. Preoperative neural functions were slight palsy in 1, moderate palsy in 5 and complete palsy in 3. In surgical treatment, neurolysis of the brachial plexus was done and it was covered by latissimus dorsi myocutaneous flap. We evaluated about dysesthesia and motor recovery after treatment for neuropathy. Follow up periods ranged from 1 to 11 years (average in 5 years). Dysesthesia improved in 6 patients and got worse in 3 patients. Motor weakness recovered in only 2 patients and got worse in 7 patients. From our results, intolerable dysesthesia which was first complaint of these patients improved. But motor function had not recovered. Our treatment was thought to be effective for extraneural factor like an compression neuropathy by scar formation and poor vascularity. But it was not effective for intraneural damage by radiation therapy. (author)

  13. Neurolysis and myocutaneous flap for radiation induced brachial plexus neuropathy

    Hirachi, Kazuhiko; Minami, Akio; Kato, Hiroyuki; Nishio, Yasuhiko [Hokkaido Univ., Sapporo (Japan). School of Medicine; Ohnishi, Nobuki

    1998-11-01

    Surgical treatment for radiation induced brachial plexus neuropathy is difficult. We followed 9 patients of radiation induced brachial plexus neuropathy who were surgically treated with neurolysis and myocutaneous flap coverage. Their ages ranged from 29 to 72 years old. Their diagnoses were breast cancer in 6 patients, lingual cancer in 1, thyroid cancer in 1 and malignant lymphoma in 1. Total dose of radiation ranged from 44 to 240 Gy. Interval from radiation therapy to our surgery ranged from 1 to 18 years (mean 6.7 years). Chief complaints were dysesthesia in 9 patients, motor weakness in 7 patients and dullach in scar formation of radiated skin in 7 patients. Preoperative neural functions were slight palsy in 1, moderate palsy in 5 and complete palsy in 3. In surgical treatment, neurolysis of the brachial plexus was done and it was covered by latissimus dorsi myocutaneous flap. We evaluated about dysesthesia and motor recovery after treatment for neuropathy. Follow up periods ranged from 1 to 11 years (average in 5 years). Dysesthesia improved in 6 patients and got worse in 3 patients. Motor weakness recovered in only 2 patients and got worse in 7 patients. From our results, intolerable dysesthesia which was first complaint of these patients improved. But motor function had not recovered. Our treatment was thought to be effective for extraneural factor like an compression neuropathy by scar formation and poor vascularity. But it was not effective for intraneural damage by radiation therapy. (author)

  14. On the many faces of Leber hereditary optic neuropathy

    Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

    1997-01-01

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between t

  15. Sight-threatening optic neuropathy is associated with paranasal lymphoma

    Takahiko Hayashi

    2010-03-01

    Full Text Available Takahiko Hayashi1, Ken Watanabe2, Yukio Tsuura3, Gengo Tsuji4, Shingo Koyama4, Jun Yoshigi4, Naoko Hirata1, Shin Yamane1, Yasuhito Iizima5, Shigeo Toyota6, Satoshi Takeuchi11Department of Ophthalmology, Yokosuka Kyosai Hospital, Japan; 2Department of Hematology, Graduate School of Medicine, Tokyo Medical and Dental University, Japan; 3Department of Pathology, Yokosuka Kyosai Hospital, Japan; 4Department of Radiology, Yokosuka Kyosai Hospital, Japan; 5Department of Ophthalmology, Yokohama City University, Japan; 6Department of Internal Medicine, Yokosuka Kyosai Hospital, JapanAbstract: Malignant lymphoma around the orbit is very rare. We present a rare case of optic neuropathy caused by lymphoma. A 61-year-old Japanese woman was referred to our hospital for evaluation of idiopathic optic neuropathy affecting her right eye. The patient was treated with steroid pulse therapy (methyl-predonisolone 1 g daily for 3 days with a presumed diagnosis of idiopathic optic neuritis. After she had been switched to oral steroid therapy, endoscopic sinus surgery had been performed, which revealed diffuse large B cell lymphoma of the ethmoidal sinus. Although R-CHOP therapy was immediately started, prolonged optic nerve compression resulted in irreversible blindness. Accordingly, patients with suspected idiopathic optic neuritis should be carefully assessed when they show a poor response, and imaging of the orbits and brain should always be done for initial diagnosis because they may have compression by a tumor.Keywords: optic neuropathy, malignant lymphoma, paranasal lymphoma, rhinogenic optic neuropathy

  16. A controlled trial of intravenous immunoglobulin in multifocal motor neuropathy

    Hahn, Angelika F; Beydoun, Said R; Lawson, Victoria;

    2013-01-01

    Intravenous immunoglobulin (IVIG) has become the standard treatment for multifocal motor neuropathy (MMN) based on limited data. To critically assess the efficacy, safety, and tolerability of 10% liquid IVIG (IVIG), 44 adults with MMN were randomized 1 : 1 to either double-blind treatment of IVIG...

  17. Brachial plexus neuropathy - A long-term outcome study

    Geertzen, JHB; Groothoff, JW; Nicolai, JP; Rietman, JS

    2000-01-01

    This retrospective study assessed the long-term outcome of brachial plexus neuropathy in 16 patients. The mean follow up was 8 years. Nine patients complained of persistent pain and muscle weakness, four had continuing problems with various activities of daily living and 11 had trouble with some hou

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

    ... article on PubMed Central Huang CL, Kuo E. Mechanisms of disease: WNK-ing at the mechanism of salt-sensitive hypertension. Nat Clin Pract Nephrol. ... Verpoorten N, De Jonghe P, Timmerman V. Disease mechanisms in hereditary sensory and autonomic neuropathies. Neurobiol Dis. ...

  19. Peripheral Neuropathy in Military Aircraft Maintenance Workers in Australia

    Guest, Maya; Attia, John R.; D'Este, Catherine A.; Boggess, May M.; Brown, Anthony M.; Gibson, Richard E.; Tavener, Meredith A.; Ross, James; Gardner, Ian; Harrex, Warren

    2011-01-01

    Objective: This study aimed to examine possible persisting peripheral neuropathy in a group who undertook fuel tank repairs on F-111 aircraft, relative to two contemporaneous comparison groups. Methods: Vibration perception threshold (VPT) was tested using biothesiometry in 614 exposed personnel, co

  20. Acute Inflammatory Demyelinating Polyradiculo-neuropathy following Antirabies Vaccine

    Bindu M

    2005-01-01

    Full Text Available Newer generation cell culture anti-rabies vaccines have become the preferred choice because of the paucity of the neurological complications. We report a case of acute inflammatory polyradiculo-neuropathy following the administration of purified chick embryo cell culture anti-rabies baccine for post exposure prophylaxis.

  1. Vitamin B12 deficiency optic neuropathy detected by asymptomatic screening

    Chu, Colin; Scanlon, Peter

    2011-01-01

    Asymptomatic bilateral optic disc swelling was detected in a 19-year-old man with type 1 diabetes through routine photographic screening for retinopathy. He was found to have significant vitamin B12 deficiency which the authors believe was the cause for the optic neuropathy. After B12 replacement, visual function and optic disc appearances returned to normal.

  2. Burden of Chemotherapy-Induced Neuropathy in School ged children

    Artan Shkoza

    2015-11-01

    Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is the most common neurological complication in cancer treatment and probably the most common toxic neuropathy in our environment. The aim of the study was to assess the incidence and discomfort caused by neuropathic symptoms in children treated for hematologic cancers. The study included all children admitted to the pediatric oncology service at the University Hospital Center “Mother Teresa”, Tirana, by the year 2011 – 2013 divided in three diagnosis groups: acute lymphoblastic leukemia, Hodgkin and non-Hodgkin’s lymphoma, or other solid tumors. In a prospective cohort setting, data were collected by standard questionnaire for symptoms and signs of neurological damage, according to The Pediatric - Modified Total Neuropathy Scale (Ped - mTNS, as well as clinical evaluation of pin sensibility, vibration sensibility, muscle strength and deep tendon reflexes (DTR. The results obtained from Ped-mTNS, showed the high incidence of sensory and motor symptoms as well as functional deficits in balance and manual dexterity in children treated with anticancer drugs. Ped-mTNS scores, as the first measure designed to assess CIPN in school-aged children, are significantly higher for children undergoing neurotoxic chemotherapy. Even though the neuropathy in these children was relatively mild, it was associated with functional deficits in balance and manual dexterity, suggesting clinical importance. An important limiting factor of this study is the exclusion of children younger than 5 years old, whom discomfort is evident but not properly evaluated.

  3. In vivo intracellular recordings from spinal lumbar motoneurones in P0-deficient mice indicate an activity-dependent axonal conduction failure in otherwise functional motoneurones

    Lehnhoff, Janna; Moldovan, Mihai; Hedegaard, Anne;

    2014-01-01

    Mice deficient for the peripheral myelin binding protein zero (P0-/-) show a progressive dysmyelinating neuropathy phenotypically resembling severe forms of Charcot-Marie-Tooth (CMT) disease. Traditionally, the progression of the disease was attributed to axonal loss, but the effect of chronic...... dysmyelination remains poorly understood. In this study, in vivo electrophysiological recordings were used to assess the function of both central and axonal components of spinal lumbar motoneurones in adult P0-/- mice.Three month old P0-/- mice (n=7) and wild type (WT) littermate controls (n=5) were...... anaesthetized with Hypnorm (0.315 mg/mL fentanyl-citrate + 10 mg/mL fluanisone), Midazolam (5 mg/mL), and sterile water, mixed in the ratio 1:1:2 (induction: 0.15mL/25g, maintenance: 0.05 mL/20 minutes, S.C.). Anaesthesia during surgery was assessed by the lack of reflexes to a short noxious pinch on the hind...

  4. Involvement of SARA in Axon and Dendrite Growth.

    Arias, Cristina Isabel; Siri, Sebastián Omar; Conde, Cecilia

    2015-01-01

    SARA (Smad Anchor for Receptor Activation) plays a crucial role in Rab5-mediated endocytosis in cell lines localizing to early endosomes where it regulates morphology and function. Here, we analyzed the role of SARA during neuronal development and tested whether it functions as a regulator of endocytic trafficking of selected axonal and membrane proteins. Suppression of SARA perturbs the appearance of juxtanuclear endocytic recycling compartments and the neurons show long axons with large growth cones. Furthermore, surface distribution of the cell adhesion molecule L1 in axons and the fusion of vesicles containing transferring receptor (TfR) in dendrites were increased in neurons where SARA was silenced. Conversely, SARA overexpression generated large early endosomes and reduced neurite outgrowth. Taken together, our findings suggest a significant contribution of SARA to key aspects of neuronal development, including neurite formation. PMID:26405814

  5. Neurofilament proteins in axonal regeneration and neurodegenerative diseases

    Haitao Wang; Minfei Wu; Chuanjun Zhan; Enyuan Ma; Maoguang Yang; Xiaoyu Yang; Yingpu Li

    2012-01-01

    Neurofilament protein is a component of the mature neuronal cytoskeleton, and it interacts with the zygosome, which is mediated by neurofilament-related proteins. Neurofilament protein regulates enzyme function and the structure of linker proteins. In addition, neurofilament gene expression plays an important role in nervous system development. Previous studies have shown that neurofilament gene transcriptional regulation is crucial for neurofilament protein expression, especially in axonal regeneration and degenerative diseases. Post-transcriptional regulation increased neurofilament protein gene transcription during axonal regeneration, ultimately resulting in a pattern of neurofilament protein expression. An expression imbalance of post-transcriptional regulatory proteins and other disorders could lead to amyotrophic lateral sclerosis or other neurodegenerative diseases. These findings indicated that after transcription, neurofilament protein regulated expression of related proteins and promoted regeneration of damaged axons, suggesting that regulation disorders could lead to neurodegenerative diseases.

  6. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    Menelaou, Evdokia; Paul, Latoya T. [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Perera, Surangi N. [Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States); Svoboda, Kurt R., E-mail: svobodak@uwm.edu [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States)

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  7. [A clinical and pathological study of diffuse axonal injury].

    Nakazawa, S; Kobayashi, S; Yokota, H; Shimura, T

    1989-03-01

    There is increasing evidence from human and experimental studies that the most important factor governing the outcome in head injury is the severity of diffuse axonal injuries. The authors have experienced 18 cases of severe diffuse axonal injury which showed post-traumatic coma for more than 24 hours and CT findings resembling those of shearing injuries of the cerebral white matter such as have been presented by Zimmerman et al. (1978). The consciousness levels on admission were 6 or less on the Glasgow Coma Scale and all cases were shown clinically to have primary brain stem injury. The main type of head trauma resulted from road traffic accidents (83%). Skull fractures were found in only 5 cases (28%). These findings suggested that acceleration/deceleration injury produce in the patients severe diffuse axonal injury. Initial ICP was below 20 mmHg in 11 cases out of 13 (85%). Parenchymal small hemorrhagic lesions of initial CT were basal ganglia (7 cases), corpus callosum (4 cases), pons (4 cases), midbrain (3 cases) and thalamus (2 cases). Extraparenchymal hemorrhagic lesions included intraventricular hemorrhage (6 cases) and subarachnoid hemorrhage (6 cases). Two autopsied cases of severe diffuse axonal injury (acute case and chronic case) showed remarkable congestion and edema in the deep part of the frontal white matter. Microscopic examination revealed marked axonal degeneration including axonal retraction ball in the corpus callosum, in the internal capsule and in the white matter of the brain stem. Glasgow Outcome Scale of the 18 patients at 3 months after the trauma made us concerned that no patients indicated good recovery or even only moderate disability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2770962

  8. Axon-glial interactions in the central nervous system

    Butt, Arthur; Bay, Virginia

    2011-01-01

    Axon-glial interactions are critical for brain information transmission and processing. In the CNS, this is a function of the major types of glia – astrocytes, oligodendrocytes and novel NG2-glia. This special issue of the Journal of Anatomy comprises contributions arising from a symposium entitled ‘Axon-glial interactions in the CNS’, held at the University of Portsmouth, UK in July 2010. The aim of the special issue is to bring together an international group of experts to demonstrate the c...

  9. A chloride channel in rat and human axons

    Strupp, Michael; Grafe, Peter

    1991-01-01

    Current recordings from single chloride channels were obtained from excised and cell-attached patches of rat and human axons. In rat axons the channels showed an outwardly rectifying current-voltage relationship with a slope conductance of 33 pS at negative membrane potentials and 65 pS at positive potentials (symmetrical 150 mM CsCl). They were measurably for cations (PNa/PCs/PCl=0.1/0.2/1). Channel currents were independent of cytoplasmatic calcium concentration. Inactivation was not observ...

  10. Tuning the orchestra: transcriptional pathways controlling axon regeneration

    Andrea Tedeschi

    2012-01-01

    Full Text Available Trauma in the adult mammalian central nervous system leads to irreversible structural and functional impairment due to failed regeneration attempts. In contrast, neurons in the peripheral nervous system exhibit a greater regenerative ability. It has been proposed that an orchestrated sequence of transcriptional events controlling the expression of specific sets of genes may be the underlying basis of an early cell-autonomous regenerative response. Understanding whether transcriptional fine tuning, in parallel with strategies aimed at counteracting extrinsic impediments promotes axon re-growth following central nervous system injuries represents an exciting challenge for future studies. Transcriptional pathways controlling axon regeneration are presented and discussed in this review.

  11. Networks of Polarized Actin Filaments in the Axon Initial Segment Provide a Mechanism for Sorting Axonal and Dendritic Proteins

    Kaori Watanabe

    2012-12-01

    Full Text Available Trafficking of proteins specifically to the axonal or somatodendritic membrane allows neurons to establish and maintain polarized compartments with distinct morphology and function. Diverse evidence suggests that an actin-dependent vesicle filter within the axon initial segment (AIS plays a critical role in polarized trafficking; however, no distinctive actin-based structures capable of comprising such a filter have been found within the AIS. Here, using correlative light and scanning electron microscopy, we visualized networks of actin filaments several microns wide within the AIS of cortical neurons in culture. Individual filaments within these patches are predominantly oriented with their plus ends facing toward the cell body, consistent with models of filter selectivity. Vesicles carrying dendritic proteins are much more likely to stop in regions occupied by the actin patches than in other regions, indicating that the patches likely prevent movement of dendritic proteins to the axon and thereby act as a vesicle filter.

  12. Membrane potential dynamics of axons in cultured hippocampal neurons probed by second-harmonic-generation imaging

    Nuriya, Mutsuo; Yasui, Masato

    2010-03-01

    The electrical properties of axons critically influence the nature of communication between neurons. However, due to their small size, direct measurement of membrane potential dynamics in intact and complex mammalian axons has been a challenge. Furthermore, quantitative optical measurements of axonal membrane potential dynamics have not been available. To characterize the basic principles of somatic voltage signal propagation in intact axonal arbors, second-harmonic-generation (SHG) imaging is applied to cultured mouse hippocampal neurons. When FM4-64 is applied extracellularly to dissociated neurons, whole axonal arbors are visualized by SHG imaging. Upon action potential generation by somatic current injection, nonattenuating action potentials are recorded in intact axonal arbors. Interestingly, however, both current- and voltage-clamp recordings suggest that nonregenerative subthreshold somatic voltage changes at the soma are poorly conveyed to these axonal sites. These results reveal the nature of membrane potential dynamics of cultured hippocampal neurons, and further show the possibility of SHG imaging in physiological investigations of axons.

  13. Prevalence of neuropathy in patients with impaired glucose tolerance using various electrophysiological tests

    Meena A Kannan

    2014-01-01

    Full Text Available Background: Neuropathy is often an associated feature woth long-standing type II diabetes mellitus. Neuropathy may occur even in subjects with impaired glucose tolerance. Objective: To study the prevalence of neuropathy using different electrophysiological techniques in subjects with impaired glucose tolerance (IGT and no other identifiable cause of neuropathy. Materials and Methods: The study was conducted on 30 age-matched controls and 58 subjects with impaired oral glucose tolerance test (OGTT attending diabetic awareness. Prediabetes was defined using World Health Organization (WHO criteria. All subjects had normal glycosylated hemoglobin HbA (1c, vitamin B12 levels, and thyroid function. Neuropathy was evaluated by nerve conduction studies (NCS performed on one upper and both lower limbs, dorsal sural nerve, medial and lateral planter nerve conductions using conventional techniques. Neuropathy was also evaluated by autononic function tests, and quantitative sensory testing (QST. The subjects were followed up for 4 years. Results: Out of 58 subjects, 19 (32.8% had neuropathy. Nerve conduction studies showed evidence of neuropathy in 14 (24.13% subjects, autonomic neuropathy was detected in 8 (13.8%, and QST was found to be abnormal in 16 (27.6% subjects. Twenty subjects (34.5% developed diabetes mellitus in the follow-up period. Conclusions: Neuropathy was detected in 32.8% subjects with IGT. Small fiber neuropathy was most common. Of all the three parameters studied, QST was found to be most sensitive technique for the detection of neuropathy. Assessment of medial plantar and dorsal sural NCS increases the sensitivity in the detection of neuropathy.

  14. Axon diameter and intra-axonal volume fraction of the corticospinal tract in idiopathic normal pressure hydrocephalus measured by q-space imaging.

    Kouhei Kamiya

    Full Text Available PURPOSE: Previous studies suggest that compression and stretching of the corticospinal tract (CST potentially cause treatable gait disturbance in patients with idiopathic normal pressure hydrocephalus (iNPH. Measurement of axon diameter with diffusion MRI has recently been used to investigate microstructural alterations in neurological diseases. In this study, we investigated alterations in the axon diameter and intra-axonal fraction of the CST in iNPH by q-space imaging (QSI analysis. METHODS: Nineteen patients with iNPH and 10 age-matched controls were recruited. QSI data were obtained with a 3-T system by using a single-shot echo planar imaging sequence with the diffusion gradient applied parallel to the antero-posterior axis. By using a two-component low-q fit model, the root mean square displacements of intra-axonal space ( =  axon diameter and intra-axonal volume fraction of the CST were calculated at the levels of the internal capsule and body of the lateral ventricle, respectively. RESULTS: Wilcoxon's rank-sum test revealed a significant increase in CST intra-axonal volume fraction at the paraventricular level in patients (p<0.001, whereas no significant difference was observed in the axon diameter. At the level of the internal capsule, neither axon diameter nor intra-axonal volume fraction differed significantly between the two groups. CONCLUSION: Our results suggest that in patients with iNPH, the CST does not undergo irreversible axonal damage but is rather compressed and/or stretched owing to pressure from the enlarged ventricle. These analyses of axon diameter and intra-axonal fraction yield insights into microstructural alterations of the CST in iNPH.

  15. Bortezomib- and thalidomide-induced peripheral neuropathy in multiple myeloma: clinical and molecular analyses of a phase 3 study.

    Tacchetti, Paola; Terragna, Carolina; Galli, Monica; Zamagni, Elena; Petrucci, Maria Teresa; Pezzi, Annalisa; Montefusco, Vittorio; Martello, Marina; Tosi, Patrizia; Baldini, Luca; Peccatori, Jacopo; Ruggieri, Miriana; Pantani, Lucia; Lazzaro, Antonio; Elice, Francesca; Rocchi, Serena; Gozzetti, Alessandro; Cavaletti, Guido; Palumbo, Antonio; Cavo, Michele

    2014-12-01

    A subanalysis of the GIMEMA-MMY-3006 trial was performed to characterize treatment-emergent peripheral neuropathy (PN) in patients randomized to thalidomide-dexamethasone (TD) or bortezomib-TD (VTD) before and after double autologous transplantation (ASCT) for multiple myeloma (MM). A total of 236 patients randomized to VTD and 238 to TD were stratified according to the emergence of grade ≥2 PN. Gene expression profiles (GEP) of CD138+ plasma cells were analyzed in 120 VTD-treated patients. The incidence of grade ≥2 PN was 35% in the VTD arm and 10% in the TD arm (P affected by emergence of grade ≥2 PN. Baseline characteristics were not risk factors for PN, while GEP analysis revealed the deregulated expression of genes implicated in cytoskeleton rearrangement, neurogenesis, and axonal guidance. In conclusion, in comparison with TD, incorporation of VTD into ASCT was associated with a higher incidence of PN which, however, was reversible in most of the patients and did not adversely affect their outcomes nor their ability to subsequently receive ASCT. GEP analysis suggests an interaction between myeloma genetic profiles and development of VTD-induced PN. PMID:25159313

  16. Synapses formed by identified retinogeniculate axons during the segregation of eye input.

    Campbell, G; Shatz, C J

    1992-01-01

    The synaptic organization of identified retinogeniculate axons was studied during the prenatal development of eye-specific layers in the LGN of the cat. During this period, retinogeniculate axons undergo stereotyped morphological changes. Retinogeniculate axons originating from one eye and passing through LGN territory destined to be solely innervated by the other eye (inappropriate territory) initially give rise to many side branches. As the eye-specific layers emerge, these axons elaborate ...

  17. Differential Axonal Projection of Mitral and Tufted Cells in the Mouse Main Olfactory System

    Shin Nagayama

    2010-09-01

    Full Text Available In the past decade, much has been elucidated regarding the functional organization of the axonal connection of olfactory sensory neurons to olfactory bulb (OB glomeruli. However, the manner in which projection neurons of the OB process odorant input and send this information to higher brain centers remains unclear. Here, we report long-range, large-scale tracing of the axonal projection patterns of OB neurons using two-photon microscopy. Tracer injection into a single glomerulus demonstrated widely distributed mitral/tufted cell axonal projections on the lateroventral surface of the mouse brain, including the anterior/posterior piriform cortex (PC and olfactory tubercle (OT. We noted two distinct groups of labeled axons: PC-orienting axons and OT-orienting axons. Each group occupied distinct parts of the lateral olfactory tract. PC-orienting axons projected axon collaterals to a wide area of the PC but only a few collaterals to the OT. OT-orienting axons densely projected axon collaterals primarily to the anterolateral OT (alOT. Different colored dye injections into the superficial and deep portions of the OB external plexiform layer revealed that the PC-orienting axon populations originated in presumed mitral cells and the OT-orienting axons in presumed tufted cells. These data suggest that although mitral and tufted cells receive similar odor signals from a shared glomerulus, they process the odor information in different ways and send their output to different higher brain centers via the PC and alOT.

  18. Quantifying mechanical force in axonal growth and guidance

    Ahmad Ibrahim Mahmoud Athamneh

    2015-09-01

    Full Text Available Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections. However, much of the details about the exact role of force in these fundamental processes remain unknown. In this review, we highlight (1 standing questions concerning the role of mechanical force in axonal growth and guidance and (2 different experimental techniques used to quantify forces in axons and growth cones. We believe that satisfying answers to these questions will require quantitative information about the relationship between elongation, forces, cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and stiffness contributing to directional growth advance. Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics. We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

  19. Traction Force and Tension Fluctuations During Axon Growth

    Jamison ePolackwich

    2015-10-01

    Full Text Available Actively generated mechanical forces play a central role in axon growthand guidance, but the mechanisms that underly force generation andregulation in growing axons remain poorly understood. We reportmeasurements of the dynamics of traction stresses from growth cones ofactively advancing axons from postnatal rat DRG neurons. By tracking themovement of the growth cone and analyzing the traction stress field froma reference frame that moves with it, we are able to show that there isa clear and consistent average stress field that underlies the complexspatial stresses present at any one time. The average stress field hasstrong maxima on the sides of the growth cone, directed inward towardthe growth cone neck. This pattern represents a contractile stresscontained within the growth cone, and a net force that is balanced bythe axon tension. Using high time-resolution measurements of the growthcone traction stresses, we show that the stress field is composed offluctuating local stress peaks, with a large number peaks that live fora short time, a population of peaks whose lifetime distribution followsan exponential decay, and a small number of very long-lived peaks. Weshow that the high time-resolution data also reveal that the tensionappears to vary randomly over short time scales, roughly consistent withthe lifetime of the stress peaks, suggesting that the tensionfluctuations originate from stochastic adhesion dynamics.

  20. Model of fasciculation and sorting in mixed populations of axons

    Chaudhuri, D.; Borowski, P.; Zápotocký, Martin

    2011-01-01

    Roč. 84, č. 2 (2011), e021908. ISSN 1539-3755 R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : axon guidance * neurogenesis * mathematical model Subject RIV: FH - Neurology Impact factor: 2.255, year: 2011

  1. Spectrins in axonal cytoskeletons: Dynamics revealed by extensions and fluctuations

    Lai, Lipeng; Cao, Jianshu

    2014-07-01

    The macroscopic properties, the properties of individual components, and how those components interact with each other are three important aspects of a composited structure. An understanding of the interplay between them is essential in the study of complex systems. Using axonal cytoskeleton as an example system, here we perform a theoretical study of slender structures that can be coarse-grained as a simple smooth three-dimensional curve. We first present a generic model for such systems based on the fundamental theorem of curves. We use this generic model to demonstrate the applicability of the well-known worm-like chain (WLC) model to the network level and investigate the situation when the system is stretched by strong forces (weakly bending limit). We specifically studied recent experimental observations that revealed the hitherto unknown periodic cytoskeleton structure of axons and measured the longitudinal fluctuations. Instead of focusing on single molecules, we apply analytical results from the WLC model to both single molecule and network levels and focus on the relations between extensions and fluctuations. We show how this approach introduces constraints to possible local dynamics of the spectrin tetramers in the axonal cytoskeleton and finally suggests simple but self-consistent dynamics of spectrins in which the spectrins in one spatial period of axons fluctuate in-sync.

  2. PTEN inhibition and axon regeneration and neural repair

    Yosuke Ohtake; Umar Hayat; Shuxin Li

    2015-01-01

    The intrinsic growth ability of all the neurons declines during development although some may grow better than others. Numerous intracellular signaling proteins and transcription factors have been shown to regulate the intrinsic growth capacity in mature neurons. Among them, PI3 kinase/Akt pathway is important for controlling axon elongation. As a negative regulator of this pathway, the tumor suppressor phosphatase and tensin homolog (PTEN) appears critical to con-trol the regenerative ability of young and adult neurons. This review will focus on recent research progress in axon regeneration and neural repair by PTEN inhibition and therapeutic potential of blocking this phosphatase for neurological disorders. Inhibition of PTEN by deletion in con-ditional knockout mice, knockdown by short-hairpin RNA, or blockade by pharmacological approaches, including administration of selective PTEN antagonist peptides, stimulates various degrees of axon regrowth in juvenile or adult rodents with central nervous system injuries. Im-portantly, post-injury PTEN suppression could enhance axonal growth and functional recovery in adult central nervous system after injury.

  3. Posterior Ischemic Optic Neuropathy Following Percutaneous Nephrolithotomy

    Mohammad Pakravan

    2008-12-01

    Full Text Available

    PURPOSE: To report a case of posterior ischemic optic neuropathy (PION following percutaneous nephrolithotomy (PCNL. CASE REPORT: A 57-year-old man with history of diabetes mellitus, hyperlipidemia and mild anemia underwent PCNL for treatment of nephrolithiasis. He noticed painless visual loss in both eyes immediately after the procedure. Visual acuity was light perception, however ophthalmologic examinations were unremarkable and the optic discs were pink with no swelling. Visual fields were severely affected, but neuro-imaging was normal. Within three months, visual acuity and visual fields improved dramatically but the optic discs became slightly pale. CONCLUSION: This is the first report of PION following PCNL. PION is a rare cause of severe visual loss following surgery. Severe blood loss, hypotension, anemia and body position during surgery are the most important risk factors. Ophthalmologists, urologists and anesthesiologists should be aware of this condition and this rare possibility should be considered prior to surgery.

  1. Hypertrophic neuropathy in Noonan syndrome with multiple lentigines.

    Maridet, Claire; Sole, Guilhem; Morice-Picard, Fanny; Taieb, Alain

    2016-06-01

    RASopathies comprise several genetic syndromes with mainly cardio-facial-cutaneous manifestations. We report a patient with Noonan syndrome with multiple lentigines (NSML) due to a PTPN11 (p.Thr468Met) mutation associated with hypertrophic neuropathy of lumbar plexus in an adult woman, initially referred for neuropathic pain. Differential diagnosis of neurofibromatosis type 1 (NF1) and other RASopathies is difficult without molecular testing. © 2016 Wiley Periodicals, Inc. PMID:26952712

  2. Pyridoxine induced neuropathy by subcutaneous administration in dogs

    Chung, Jin-Young; Choi, Jung-Hoon; HWANG, Cheol-Yong; Youn, Hwa-Young

    2008-01-01

    To construct a sensory neuropathy model, excess pyridoxine (150 mg/kg s.i.d.) was injected subcutaneously in dogs over a period of 7 days. During the administrations period, the dogs experienced body weight reduction and proprioceptive loss involving the hindquarters. After pyridoxine administration was completed, electrophysiological recordings showed that the M wave remained at a normal state, but the H-reflex of the treated dogs disappeared at 7 days. The dorsal funiculus of L4 was disrupt...

  3. Clinical Research on Acupuncture Treatment of Diabetic Peripheral Neuropathy

    QIAN Wei-hua; QIAN Hong; WU Tong; BEI Yan-hui; LI Lan; QING Liang-cai

    2004-01-01

    目的:探讨针刺治疗糖尿病周围神经病变的相关机理.方法:运用针刺疗法治疗糖尿病周围神经病变,并与口服钙离子拮抗剂加维生素疗法进行随机对照观察,同时作肌电图检测分析.结果:针刺治疗糖尿病周围神经病变可不同程度地改善病人的肢体麻木、疼痛和感觉异常等临床症状,肌电图结果提示神经运动传导速度和感觉传导速度也有明显改善.结论:针刺治疗糖尿病周围神经病变的临床疗效明显优于口服钙离子拮抗剂加维生素治疗.%Purpose: To investigate the mechanism of acupuncture treatment of diabetic peripheral neuropathy. Methods: Acupuncture therapy was used to treat diabetic peripheral neuropathy, and compared with oral calcium antagonist and vitamin therapy by random control observation.Electromyography was performed for analysis at the same time. Results: Acupuncture treatment alleviated symptoms such as extremity numbness, pain and paresthesia in varying degrees in diabetic patients with peripheral neuropathy. The results of electromyography showed a marked improvement in motor and sensory conduction velocities. Conclusion: It is indicated that acupuncture therapy is markedly superior to oral calcium antagonist and vitamin therapy in clinical effect on diabetic peripheral neuropathy, and electromyographic recovery.

  4. Updates in diabetic peripheral neuropathy [version 1; referees: 3 approved

    Kelsey Juster-Switlyk; Gordon Smith, A.

    2016-01-01

    Diabetes has become one of the largest global health-care problems of the 21st century. According to the Centers for Disease Control and Prevention, the population prevalence of diabetes in the US is approaching 10% and is increasing by 5% each year. Diabetic neuropathy is the most common complication associated with diabetes mellitus. Diabetes causes a broad spectrum of neuropathic complications, including acute and chronic forms affecting each level of the peripheral nerve, from the root to...

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

    Reife, Michael D; Coulis, Christopher M

    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 ...

  6. Skin biopsies in the evaluation of atypical optic neuropathies.

    Bielory, L; Kupersmith, M; Warren, F; Bystryn, J; Frohman, L

    1993-01-01

    Patients with atypical clinical presentations of common optic neuropathies such as optic neuritis (ON), anterior ischemic optic neuropathy (AION), or optic neuropathy of unknown etiology (UON) are difficult to distinguish from inflammatory autoimmune optic neuropathy (AON) which is typically associated with a poor visual prognosis, unless treated with high doses of corticosteroids and/or immunosuppressive agents. The authors retrospectively evaluated 34 patients [AON (n = 12); AION (n = 5); ON (n = 9); UON (n = 8)] with visual loss which deteriorated over weeks to months or followed an atypical course, for the presence of immunological markers suggestive of AON. These markers included serological testing for antiphospholipid (APA) and antinuclear (ANA) antibodies, and evaluation of histopathologic and immunofluorescent staining of skin biopsies. All patients underwent a skin biopsy. Four of the 12 patients with AON had urticarial cutaneous lesions which revealed leukocytoclastic and/or lymphohistiocytic vasculitis. Seven of the remaining eight AON patients had skin biopsies of non-lesional skin which revealed immunoreactant deposition. Seven of the 21 skin biopsies obtained from the non-AON patients had findings of vacuolization or mild perivascular infiltration of lymphocytes (n = 5) and immunofluorescent deposits (n = 2). Abnormal skin biopsies (92%;p = 0.0009) and circulating APA (82%; p = 0.013) were common in AON patients while ANA was not statistically increased in AON patients (p = 0.06) when compared to the remaining patients as a whole. AON patients typically demonstrate evidence of systemic autoimmune involvement, as manifested by cutaneous abnormalities such as urticarial vasculitis and/or immunoreactant deposition and circulating APA. These may serve as markers for identifying AON patients who may be treated with immunomodulatory agents. PMID:22822778

  7. Pathogenesis of diabetic neuropathy: bad to the bone

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

    2011-01-01

    Insulin and proinsulin are normally produced only by the pancreas and thymus. We detected in diabetic rodents the presence of extra pancreatic proinsulin-producing bone marrow-derived cells (PI-BMDCs) in the BM, liver, and fat. In mice and rats with diabetic neuropathy, we also found proinsulin-producing cells in the sciatic nerve and neurons of the dorsal root ganglion (DRG). BM transplantation experiments using genetically marked donor and recipient mice showed that the proinsulin-producing...

  8. Entrapment neuropathy about the foot and ankle: an update.

    Pomeroy, Gregory; Wilton, James; Anthony, Steven

    2015-01-01

    Occurrences of entrapment neuropathies of the lower extremity are relatively infrequent; therefore, these conditions may be underappreciated and difficult to diagnose. Understanding the anatomy of the peripheral nerves and their potential entrapment sites is essential. A detailed physical examination and judicious use of imaging modalities are also vital when establishing a diagnosis. Once an accurate diagnosis is obtained, treatment is aimed at reducing external pressure, minimizing inflammation, correcting any causative foot and ankle deformities, and ultimately releasing any constrictive tissues. PMID:25538131

  9. IH activity is increased in populations of slow versus fast motor axons of the rat.

    Chad eLorenz

    2014-09-01

    Full Text Available Much is known about the electrophysiological variation in motoneuron somata across different motor units. However comparatively less is known about electrophysiological variation in motor axons and how this could impact function or electrodiagnosis in healthy or diseased states. We performed nerve excitability testing on two groups of motor axons in Sprague-Dawley rats that are known to differ significantly in their chronic daily activity patterns and in the relative proportion of motor unit types: one group innervating the soleus (slow motor axons and the other group innervating the tibialis anterior (fast motor axons muscles. We found that slow motor axons have significantly larger accommodation compared to fast motor axons upon application of a 100 ms hyperpolarizing conditioning stimulus that is 40% of axon threshold (Z = 3.24, p = 0.001 or 20% of axon threshold (Z = 2.67, p = 0.008. Slow motor axons had larger accommodation to hyperpolarizing currents in the current-threshold measurement (-80% Z = 3.07, p = 0.002; -90% Z = 2.98, p = 0.003. In addition, we found that slow motor axons have a significantly smaller rheobase than fast motor axons (Z = -1.99, p = 0.047 accompanied by a lower threshold in stimulus-response curves. The results provide evidence that slow motor axons have greater activity of the hyperpolarization-activated inwardly rectifying cation conductance (IH than fast motor axons. It is possible that this difference between fast and slow axons is caused by an adaptation to their chronic differences in daily activity patterns, and that this adaptation might have a functional effect on the motor unit. Moreover, these findings indicate that slow and fast motor axons may react differently to pathological conditions.

  10. White matter involvement after TBI: Clues to axon and myelin repair capacity.

    Armstrong, Regina C; Mierzwa, Amanda J; Marion, Christina M; Sullivan, Genevieve M

    2016-01-01

    Impact-acceleration forces to the head cause traumatic brain injury (TBI) with damage in white matter tracts comprised of long axons traversing the brain. White matter injury after TBI involves both traumatic axonal injury (TAI) and myelin pathology that evolves throughout the post-injury time course. The axon response to initial mechanical forces and secondary insults follows the process of Wallerian degeneration, which initiates as a potentially reversible phase of intra-axonal damage and proceeds to an irreversible phase of axon fragmentation. Distal to sites of axon disconnection, myelin sheaths remain for prolonged periods, which may activate neuroinflammation and inhibit axon regeneration. In addition to TAI, TBI can cause demyelination of intact axons. These evolving features of axon and myelin pathology also represent opportunities for repair. In experimental TBI, demyelinated axons exhibit remyelination, which can serve to both protect axons and facilitate recovery of function. Myelin remodeling may also contribute to neuroplasticity. Efficient clearance of myelin debris is a potential target to attenuate the progression of chronic pathology. During the early phase of Wallerian degeneration, interventions that prevent the transition from reversible damage to axon disconnection warrant the highest priority, based on the poor regenerative capacity of axons in the CNS. Clinical evaluation of TBI will need to address the challenge of accurately detecting the extent and stage of axon damage. Distinguishing the complex white matter changes associated with axons and myelin is necessary for interpreting advanced neuroimaging approaches and for identifying a broader range of therapeutic opportunities to improve outcome after TBI. PMID:25697845

  11. Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy

    Aparna Areti; Veera Ganesh Yerra; VGM Naidu; Ashutosh Kumar

    2014-01-01

    Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN) remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The curr...

  12. Increased Carrying Angle is a Risk Factor for Nontraumatic Ulnar Neuropathy at the Elbow

    Chang, Chein-Wei; Wang, Yi-Chian; Chu, Chang-Hung

    2008-01-01

    The literature suggests a possible relationship between carrying angle and nontrauma-related ulnar neuropathy. To confirm that relationship, we asked whether carrying angle is a risk factor in patients with nontrauma-related ulnar neuropathy. We measured the carrying angles of the elbow in 36 patients with a clinically and electrophysiologically confirmed diagnosis of nontraumatic ulnar neuropathy at the elbow and in 50 healthy control subjects. Correlation analysis was performed between carr...

  13. Role of nitrosative and oxidative stress in neuropathy in patients with type 2 diabetes mellitus

    Marwan S Al-Nimer

    2012-01-01

    Full Text Available Objectives : Evidences of oxidative and/or nitrosative stress in type 2 diabetes mellitus were demonstrated in experimental and human studies. This study is aimed to assess the serum peroxynitrite and oxidized lipoproteins in patients with type 2 diabetes mellitus presented with clinical and laboratory evidences of peripheral neuropathy. Materials and Methods : Eighty four patients with type 2 diabetes mellitus (51 of them had neuropathy and 31 apparent healthy subjects were studied in the unit of neurophysiology at the University Hospital of Medical College, Al-Nahrin University in Baghdad, Iraq. Neuropathy total symptom score (NTSS, neuropathy impairment score in the lower leg (NIS-LL, and nerve conduction velocity of sensory (ulnar and sural and motor (ulnar and common peroneal nerves were used to assess the neuropathy. Fasting venous blood was obtained from each participant for the determination of serum glucose and oxidized lipoproteins. Results: The electrophysiology study revealed significant decrease in conduction velocity of ulnar (sensory and motor components, sural, and common peroneal nerves in diabetic neuropathy compared to diabetics without neuropathy and healthy subjects. Significant high level of serum peroxynitrite was found in diabetic patients with or without neuropathy compared with non-diabetics. The changes in serum-oxidized lipoproteins in patients with diabetics with or without neuropathy were non-significantly differed from healthy subjects. Neither nitrosative stress nor oxidative stress indices correlated with the variables that are related to the neuropathy. Conclusion: It concludes that evidence of nitrosative and to less extent the oxidative stress is associated with neuropathy in type 2 diabetes mellitus and their indices not correlated with variables related to neuropathy.

  14. Lipid peroxidation and superoxide dismutase activities in patients with type 2 diabetes complicated with peripheral neuropathy

    Shilpashree Y. Dhanajaya; Tejaswi H. Lokanathan

    2016-01-01

    Background: Diabetic neuropathy is one of most common complication of diabetes. The suggested factor for the development of diabetic neuropathy is increased lipid peroxidation which is a result of enhanced free radical generation and decreased antioxidant defence. Methods: This cross sectional study was carried out in the department of Biochemistry, JSS Medical College, Mysore. Thirty patients with diabetic neuropathy, 30 diabetics without any complications and 30 age and sex matched co...

  15. Small Fiber Neuropathy Associated with Hyperlipidemia: Utility of Cutaneous Silent Periods and Autonomic Tests

    Morkavuk, G.; Leventoglu, A.

    2014-01-01

    Background. Established electrophysiological methods have limited clinical utility in the diagnosis of small fiber neuropathy. The cutaneous silent period (CSP) may be useful as a method for the evaluation of smaller and unmyelinated fiber dysfunctions. Hyperlipidemia is a very rare cause of small fiber neuropathy. In this study, hyperlipidemia and small fiber neuropathy in symptomatic patients with normal nerve conduction studies were evaluated with autonomic tests and cutaneous silent perio...

  16. Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy

    Fenrich, Keith K; Skelton, Nicole; MacDermid, Victoria E;

    2007-01-01

    Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injur...

  17. Are electrophysiological criteria useful in distinguishing childhood demyelinating neuropathies?

    Potulska-Chromik, Anna; Ryniewicz, Barbara; Aragon-Gawinska, Karolina; Kabzinska, Dagmara; Seroka, Andrzej; Lipowska, Marta; Kaminska, Anna M; Kostera-Pruszczyk, Anna

    2016-03-01

    Childhood chronic inflammatory demyelinating polyneuropathy (CIDP) needs to be differentiated from hereditary neuropathy. We aimed to validate existing CIDP nerve conduction study (NCS) criteria in a group of children with demyelinating neuropathies of chronic or subacute onset. Retrospective analysis of clinical and NCS results in 18 children with CIDP, 7 with hereditary neuropathy with pressure palsy (HNPP), and 24 with Charcot-Marie-Tooth 1a (CMT1a). AAN and EFNS electrodiagnostic CIDP criteria were fulfilled in 17 of 18 CIDP, 3 of 7 HNPP, and 23 of 24 CMT1a patients. A distal compound muscle action potential (dCMAP) of >9 ms was observed in 14 of 18 CIDP patients but not in any patients with HNPP. Abnormal median/normal sural SNAP (AMNS) and a 10 m/s difference between conduction velocities (CV) of two corresponding nerves were not observed in any CMT1a patients. NCS in CMT1a, HNPP, and CIDP reflect demyelination. dCMAP duration, sensory AMNS, and a 10 m/s CV difference parameter are most useful in the differential diagnosis of pediatric CIDP. PMID:26663344

  18. Effect of Large Dose Methylcobalamin on Diabetic Peripheral Neuropathy

    2005-01-01

    The effects of large dose methylcobalamin injection on diabetic peripheral neuropathy in patients were observed to observe the subjective symptom of diabetic perpheral neuropathy (DPN) patients and detect the motor nerve conduction velocity (MCV) and sense nerve conduction velocity (SCV). Fifteen patients were received large dose methylcobalamin injection for two weeks as treatment group, another eleven patients were received muscular injection VitB1 100mg/ d, VitB12 500ug/ d for two weeks as control group. After 2 weeks treatment the subjective symptoms and signs were significantly improved with a total effective rate of 82.9% in the treatment group however the effective rate only has 52.0% in the control group. The result has obvious difference in statistics nerve MCV in median common peroneal nerve, SCV in median and superficial peroneal nerve were improved significantly in the treatment group and no such changes were observed in the control group. So, large dose methylcobalamin is an effective and safe agent for treatment of diabetic peripheral neuropathy.

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

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

    2015-08-01

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

  20. Pathogenesis of diabetic neuropathy: focus on neurovascular mechanisms.

    Sytze Van Dam, P; Cotter, Mary A; Bravenboer, Bert; Cameron, Norman E

    2013-11-01

    Neuropathies of the peripheral and autonomic nervous systems affect up to half of all people with diabetes, and are major risk factors for foot ulceration and amputation. The aetiology is multifactorial: metabolic changes in diabetes may directly affect neural tissue, but importantly, neurodegenerative changes are precipitated by compromised nerve vascular supply. Experiments in animal models of diabetic neuropathy suggest that similar metabolic sequelae affect neurons and vasa nervorum endothelium. These include elevated polyol pathway activity, oxidative stress, the formation of advanced glycation and lipoxidation end products, and various pro-inflammatory changes such as elevated protein kinase C, nuclear factor κB and p38 mitogen activated protein kinase signalling. These mechanisms do not work in isolation but strongly interact in a mutually facilitatory fashion. Nitrosative stress and the induction of the enzyme poly (ADP-ribose) polymerase form one important link between physiological stressors such as reactive oxygen species and the pro-inflammatory mechanisms. Recently, evidence points to endoplasmic stress and the unfolded protein response as forming another crucial link. This review focuses on the aetiopathogenesis of neurovascular changes in diabetic neuropathy, elucidated in animal studies, and on putative therapeutic targets the majority of which have yet to be tested for efficacy in clinical trials. PMID:23872412

  1. Protection of Trigonelline on Experimental Diabetic Peripheral Neuropathy

    Ji-Yin Zhou

    2012-01-01

    Full Text Available The mechanisms leading to diabetic peripheral neuropathy are complex and there is no effective drug to treat it. As an active component of several traditional Chinese medicines, trigonelline has beneficial effects on diabetes with hyperlipidemia. The protective effects and the mechanism of trigonelline on diabetic peripheral neuropathy were evaluated in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Rats were divided into four groups at the end of week 2: control, diabetes, diabetes + trigonelline (40 mg/kg, and diabetes + sitagliptin (4 mg/kg. After 48-week treatment, technologies of nerve conduction, cold and hot immersion test, transmission electron microscopy, real-time PCR, and Western blotting were applied. Serum glucose, serum insulin, insulin sensitivity index, lipid parameters, body weight, sciatic nerve conduction velocity, nociception, glucagon-like peptide-1 receptor mRNA and protein, total and phosphorylated p38 mitogen-activated protein kinases protein expression, malonaldehyde content, and superoxide dismutase activity were altered in diabetic rats, and were near control levels treated with trigonelline. Slight micropathological changes existed in sciatic nerve of trigonelline-treated diabetic rats. These findings suggest that trigonelline has beneficial effects for diabetic peripheral neuropathy through glucagon-like peptide-1 receptor/p38 mitogen-activated protein kinases signaling pathway, nerve conduction velocity, antioxidant enzyme activity, improving micropathological changes of sciatic nerve and decreasing lipid peroxidation.

  2. Amiodarone-Associated Optic Neuropathy: A Critical Review

    Passman, Rod S.; Bennett, Charles L.; Purpura, Joseph M.; Kapur, Rashmi; Johnson, Lenworth N.; Raisch, Dennis W.; West, Dennis P.; Edwards, Beatrice J.; Belknap, Steven M.; Liebling, Dustin B.; Fisher, Mathew J.; Samaras, Athena T.; Jones, Lisa-Gaye A.; Tulas, Katrina-Marie E.; McKoy, June M.

    2011-01-01

    Although amiodarone is the most commonly prescribed antiarrhythmic drug, its use is limited by serious toxicities, including optic neuropathy. Current reports of amiodarone associated optic neuropathy identified from the Food and Drug Administration's Adverse Event Reporting System (FDA-AERS) and published case reports were reviewed. A total of 296 reports were identified: 214 from AERS, 59 from published case reports, and 23 from adverse events reports for patients enrolled in clinical trials. Mean duration of amiodarone therapy before vision loss was 9 months (range 1-84 months). Insidious onset of amiodarone associated optic neuropathy (44%) was the most common presentation, and nearly one-third were asymptomatic. Optic disc edema was present in 85% of cases. Following drug cessation, 58% had improved visual acuity, 21% were unchanged, and 21% had further decreased visual acuity. Legal blindness (< 20/200) was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance of patients during the tenure of amiodarone administration is warranted. PMID:22385784

  3. Peripheral neuropathy in primary HIV infection associates with systemic and central nervous system immune activation

    Wang, SXY; Ho, EL; Grill, M.; Lee, E.; Peterson, J.; Robertson, K; Fuchs, D.; Sinclair, E.; Price, RW; Spudich, S

    2014-01-01

    Copyright © 2014 by Lippincott Williams & Wilkins. Background: Peripheral neuropathy (PN) is a frequent complication of chronic HIV infection. We prospectively studied individuals with primary HIV infection (

  4. Association between the level of serum vitamin D and peripheral neuropathy in type 2 diabetic patients

    张吉平

    2014-01-01

    Objective To evaluate the relationship between 25-(OH)vitamin D[25-(OH)D]level and peripheral neuropathy in patients with type 2 diabetes mellitus.Methods Eighty patients with type 2 diabetes mellitus were enrolled in this cross-sectional study,including 37 subjects with and 43 without diabetic neuropathy.Anthropometric data was collected and serum levels of 25-(OH)D,Hb A1C,blood lipid,and hepatic and renal functions were determined in all patients.Results Serum 25-(OH)D level was significantly lower in patients with diabetic neuropathy compared to those without neuropathy

  5. Sciatic Neuropathy: Case Report and Discussion of the Literature on Postoperative Sciatic Neuropathy and Sciatic Nerve Tumors

    Feinberg, Joseph; Sethi, Shikha

    2006-01-01

    Sciatic nerve injury and dysfunction is not an uncommon cause of lower extremity symptoms in a musculoskeletal practice. We present the case of a man who presented with lower extremity weakness, pain, and cramps, and was initially diagnosed at an outside institution with bilateral S1 radiculopathies and recommended for spine surgery. He came to us for a second opinion. Electrodiagnostic testing revealed an isolated sciatic neuropathy and the patient was referred for imaging, which showed a sc...

  6. Alterations of mitochondrial dynamics allow retrograde propagation of locally initiated axonal insults.

    Lassus, Benjamin; Magifico, Sebastien; Pignon, Sandra; Belenguer, Pascale; Miquel, Marie-Christine; Peyrin, Jean-Michel

    2016-01-01

    In chronic neurodegenerative syndromes, neurons progressively die through a generalized retraction pattern triggering retrograde axonal degeneration toward the cell bodies, which molecular mechanisms remain elusive. Recent observations suggest that direct activation of pro-apoptotic signaling in axons triggers local degenerative events associated with early alteration of axonal mitochondrial dynamics. This raises the question of the role of mitochondrial dynamics on both axonal vulnerability stress and their implication in the spreading of damages toward unchallenged parts of the neuron. Here, using microfluidic chambers, we assessed the consequences of interfering with OPA1 and DRP1 proteins on axonal degeneration induced by local application of rotenone. We found that pharmacological inhibition of mitochondrial fission prevented axonal damage induced by rotenone, in low glucose conditions. While alteration of mitochondrial dynamics per se did not lead to spontaneous axonal degeneration, it dramatically enhanced axonal vulnerability to rotenone, which had no effect in normal glucose conditions, and promoted retrograde spreading of axonal degeneration toward the cell body. Altogether, our results suggest a mitochondrial priming effect in axons as a key process of axonal degeneration. In the context of neurodegenerative diseases, like Parkinson's and Alzheimer's, mitochondria fragmentation could hasten neuronal death and initiate spatial dispersion of locally induced degenerative events. PMID:27604820

  7. The role of T-cadherin in axonal pathway formation in neocortical circuits.

    Hayano, Yuki; Zhao, Hong; Kobayashi, Hiroaki; Takeuchi, Kosei; Norioka, Shigemi; Yamamoto, Nobuhiko

    2014-12-01

    Cortical efferent and afferent fibers are arranged in a stereotyped pattern in the intermediate zone (IZ). Here, we studied the mechanism of axonal pathway formation by identifying a molecule that is expressed in a subset of cortical axons in the rat. We found that T-cadherin (T-cad), a member of the cadherin family, is expressed in deep-layer cell axons projecting to subcortical structures, but not in upper layer callosal axons projecting to the contralateral cortex. Ectopic expression of T-cad in upper layer cells induced axons to project toward subcortical structures via the upper part of the IZ. Moreover, the axons of deep-layer cells in which T-cad expression was suppressed by RNAi projected towards the contralateral cortex via an aberrant route. These results suggest that T-cad is involved in axonal pathway formation in the developing cortex. PMID:25468941

  8. Axonal degeneration affects muscle density in older men and women.

    Lauretani, Fulvio; Bandinelli, Stefania; Bartali, Benedetta; Di Iorio, Angelo; Giacomini, Vittoria; Corsi, Anna Maria; Guralnik, Jack M; Ferrucci, Luigi

    2006-08-01

    Using data from InCHIANTI, a prospective population-based survey of older persons, we examined the relationship of peroneal nerve conduction velocity (NCV, a measure of nerve myelination) and compound muscle action potential (CMAP, a measure of axonal degeneration) with calf muscle mass and density, two complementary measures of sarcopenia. NCV and CMAP were assessed by surface electroneurography of the right peroneal nerve conducted in 1162 participants, 515 men and 647 women, age 21-96 years, free of major neurological diseases. Cross-sectional muscle area and calf muscle density were measured using peripheral quantitative computerized tomography (pQCT). Both nerve and muscle parameters declined with age although in most cases the decline was not linear. In both sexes, CMAP, but not NCV, was independently and significantly associated with calf muscle density. These findings suggest that intrinsic changes in the muscle tissue are partially caused by a reduction in the number of motor axons. PMID:16085338

  9. Missed connections: photoreceptor axon seeks target neuron for synaptogenesis.

    Astigarraga, Sergio; Hofmeyer, Kerstin; Treisman, Jessica E

    2010-08-01

    Extending axons must choose the appropriate synaptic target cells in order to assemble functional neural circuitry. The axons of the Drosophila color-sensitive photoreceptors R7 and R8 project as a single fascicle from each ommatidium, but their terminals are segregated into distinct layers within their target region. Recent studies have begun to reveal the molecular mechanisms that establish this projection pattern. Both homophilic adhesion molecules and specific ligand-receptor interactions make important contributions to stabilizing R7 and R8 terminals in the appropriate target layers. These cell recognition molecules are regulated by the same transcription factors that control R7 and R8 cell fates. Autocrine and repulsive signaling mechanisms prevent photoreceptor terminals from encroaching on their neighbors, preserving the spatial resolution of visual information. PMID:20434326

  10. Bazooka mediates secondary axon morphology in Drosophila brain lineages

    Hartenstein Volker; Spindler Shana R

    2011-01-01

    Abstract In the Drosophila brain, neural lineages project bundled axon tracts into a central neuropile. Each lineage exhibits a stereotypical branching pattern and trajectory, which distinguish it from other lineages. In this study, we used a multilineage approach to explore the neural function of the Par-complex member Par3/Bazooka in vivo. Drosophila bazooka is expressed in post-mitotic neurons of the larval brain and localizes within neurons in a lineage-dependent manner. The fact that mul...

  11. Craniocerebral trauma. Magnetic resonance imaging of diffuse axonal injury

    Acceleration-deceleration rotational brain trauma is a common cause of disability or death in young adults and often leads to a focal destruction of axons. The resulting pathology, axonal shear injury is referred to as diffuse axonal injury (DAI). The DAI-associated lesions occur bilaterally, are widely dispersed and have been observed in the surface and deep white matter. They are found near to and far from the impact site. When DAI is clinically suspected, magnetic resonance imaging (MRI) is the method of choice for further clarification, especially in patients where cranial computed tomography (CT) is inconspicuous. To investigate the presence of DAI after traumatic brain injury (TBI), a multimodal MRI approach is applied including the common structural and also functional imaging sequences. For structural MRI, fluid-attenuated inversion recovery (FLAIR) weighted and susceptibility contrast imaging (SWI) are the sequences mainly used. The SWI technique is extremely sensitive to blood breakdown products, which appear as small signal voids at three locations, at the gray-white interface, in the corpus callosum and in the brain stem. Functional MRI comprises a group of constantly developing techniques that have great potential in optimal evaluation of the white matter in patients after craniocerebral trauma. These imaging techniques allow the visualization of changes associated with shear injuries, such as functional impairment of axons and decreased blood flow and abnormal metabolic activity of the brain parts affected. The multimodal MRI approach in patients with DAI results in a more detailed and differentiated representation of the underlying pathophysiological changes of the injured nerve tracts and helps to improve the diagnostic and prognostic accuracy of MRI. When DAI is suspected multimodal MRI should be performed as soon as possible after craniocerebral injury. (orig.)

  12. Estimating neuronal connectivity from axonal and dendritic density fields

    Jaap evan Pelt

    2013-11-01

    Full Text Available Neurons innervate space by extending axonal and dendritic arborizations. When axons and dendrites come in close proximity of each other, synapses between neurons can be formed. Neurons vary greatly in their morphologies and synaptic connections with other neurons. The size and shape of the arborizations determine the way neurons innervate space. A neuron may therefore be characterized by the spatial distribution of its axonal and dendritic 'mass'. A population mean 'mass' density field of a particular neuron type can be obtained by averaging over the individual variations in neuron geometries. Connectivity in terms of candidate synaptic contacts between neurons can be determined directly on the basis of their arborizations but also indirectly on the basis of their density fields. To decide when a candidate synapse can be formed, we previously developed a criterion defining that axonal and dendritic line pieces should cross in 3D and have an orthogonal distance less than a threshold value. In this paper, we developed new methodology for applying this criterion to density fields. We show that estimates of the number of contacts between neuron pairs calculated from their density fields are fully consistent with the number of contacts calculated from the actual arborizations. However, the estimation of the connection probability and the expected number of contacts per connection cannot be calculated directly from density fields, because density fields do not carry anymore the correlative structure in the spatial distribution of synaptic contacts. Alternatively, these two connectivity measures can be estimated from the expected number of contacts by using empirical mapping functions. The neurons used for the validation studies were generated by our neuron simulator NETMORPH. An example is given of the estimation of average connectivity and Euclidean pre- and postsynaptic distance distributions in a network of neurons represented by their population

  13. Tau phosphorylation affects its axonal transport and degradation

    Rodríguez-Martín, Teresa; Cuchillo-Ibáñez, Inmaculada; Noble, Wendy; Nyenya, Fanon; Anderton, Brian H; Hanger, Diane P.

    2013-01-01

    Phosphorylated forms of microtubule-associated protein tau accumulate in neurofibrillary tangles in Alzheimer's disease. To investigate the effects of specific phosphorylated tau residues on its function, wild type or phosphomutant tau was expressed in cells. Elevated tau phosphorylation decreased its microtubule binding and bundling, and increased the number of motile tau particles, without affecting axonal transport kinetics. In contrast, reducing tau phosphorylation enhanced the amount of ...

  14. Abnormal Corticospinal Excitability in Traumatic Diffuse Axonal Brain Injury

    Bernabeu, Montse; Demirtas-Tatlidede, Asli; Opisso, Eloy; Lopez, Raquel; Tormos, Jose Mª; Pascual-Leone, Alvaro

    2009-01-01

    This study aimed to investigate the cortical motor excitability characteristics in diffuse axonal injury (DAI) due to severe traumatic brain injury (TBI). A variety of excitatory and inhibitory transcranial magnetic stimulation (TMS) paradigms were applied to primary motor cortices of 17 patients and 11 healthy controls. The parameters of testing included resting motor threshold (MT), motor evoked potential (MEP) area under the curve, input-output curves, MEP variability, and silent period (S...

  15. Slowing of the axonal transport of neurofilament proteins during development

    We examined age-dependent changes in neurofilament transport in motor axons of the rat sciatic nerve. SDS-PAGE and gel fluorography confirmed that the distribution of labeled neurofilament triplet protein coincides with the major slow component a (SCa) wave in these neurons. The velocity of neurofilament transport was calculated on the basis of the location of the 50th percentile of radioactivity in this wave 33 days after motor neurons were labeled by the intraspinal administration of [3H]leucine and [3H]lysine. Overall, the velocity fell from 1.95 mm/day at 3 weeks of age to 1.12 mm/day at 20 weeks. Between 3 and 10 weeks, it fell at a 6-fold higher rate (0.096 mm/day/week) than between 10 and 20 weeks (0.016 mm/day/week). We also found a marked change in the shape of the slow component wave during development. It appeared to consist of several overlapping peaks moving at slightly different velocities in animals 10 weeks of age or less as compared to a single slower moving peak at 20 weeks. We propose that the velocity of slow axonal transport reflects the level of maturation of the neuron, and that the presence of several overlapping peaks of transported radioactivity in the sciatic nerve of younger animals reflects the presence of several populations of motor axons at different stages of development. We also discuss the relationship between changes in the velocity of neurofilament transport and alterations in the composition of the cytoskeleton that occur as the axon grows in caliber during postnatal development

  16. Voluntary exercise increases axonal regeneration from sensory neurons

    Molteni, Raffaella; Zheng, Jun-Qi; Ying, Zhe; Gómez-Pinilla, Fernando; Twiss, Jeffery L

    2004-01-01

    Recent advances in understanding the role of neurotrophins on activity-dependent plasticity have provided insight into how behavior can affect specific aspects of neuronal biology. We present evidence that voluntary exercise can prime adult dorsal root ganglion neurons for increased axonal regeneration through a neurotrophin-dependent mechanism. Dorsal root ganglion neurons showed an increase in neurite outgrowth when cultured from animals that had undergone 3 or 7 days of exercise compared w...

  17. Adult motor axons preferentially reinnervate predegenerated muscle nerve

    M. Abdullah; O'Daly, A.; A Vyas; Rohde, C.; Brushart, T.M.

    2013-01-01

    Preferential motor reinnervation (PMR) is the tendency for motor axons regenerating after repair of mixed nerve to reinnervate muscle nerve and/or muscle rather than cutaneous nerve or skin. PMR may occur in response to the peripheral nerve pathway alone in juvenile rats (Brushart, 1993; Redett et al., 2005), yet the ability to identify and respond to specific pathway markers is reportedly lost in adults (Uschold et al., 2007). The experiments reported here evaluate the relative roles of path...

  18. White matter microstructure from nonparametric axon diameter distribution mapping.

    Benjamini, Dan; Komlosh, Michal E; Holtzclaw, Lynne A; Nevo, Uri; Basser, Peter J

    2016-07-15

    We report the development of a double diffusion encoding (DDE) MRI method to estimate and map the axon diameter distribution (ADD) within an imaging volume. A variety of biological processes, ranging from development to disease and trauma, may lead to changes in the ADD in the central and peripheral nervous systems. Unlike previously proposed methods, this ADD experimental design and estimation framework employs a more general, nonparametric approach, without a priori assumptions about the underlying form of the ADD, making it suitable to analyze abnormal tissue. In the current study, this framework was used on an ex vivo ferret spinal cord, while emphasizing the way in which the ADD can be weighted by either the number or the volume of the axons. The different weightings, which result in different spatial contrasts, were considered throughout this work. DDE data were analyzed to derive spatially resolved maps of average axon diameter, ADD variance, and extra-axonal volume fraction, along with a novel sub-micron restricted structures map. The morphological information contained in these maps was then used to segment white matter into distinct domains by using a proposed k-means clustering algorithm with spatial contiguity and left-right symmetry constraints, resulting in identifiable white matter tracks. The method was validated by comparing histological measures to the estimated ADDs using a quantitative similarity metric, resulting in good agreement. With further acquisition acceleration and experimental parameters adjustments, this ADD estimation framework could be first used preclinically, and eventually clinically, enabling a wide range of neuroimaging applications for improved understanding of neurodegenerative pathologies and assessing microstructural changes resulting from trauma. PMID:27126002

  19. Intralimb Coordination Patterns in Absent, Mild, and Severe Stages of Diabetic Neuropathy: Looking Beyond Kinematic Analysis of Gait Cycle

    Liu Chiao Yi; Cristina D Sartor; Francis Trombini Souza; Isabel C. N. Sacco

    2016-01-01

    Aim Diabetes Mellitus progressively leads to impairments in stability and joint motion and might affect coordination patterns, mainly due to neuropathy. This study aims to describe changes in intralimb joint coordination in healthy individuals and patients with absent, mild and, severe stages of neuropathy. Methods Forty-seven diabetic patients were classified into three groups of neuropathic severity by a fuzzy model: 18 without neuropathy (DIAB), 7 with mild neuropathy (MILD), and 22 with m...

  20. Retinal glia promote dorsal root ganglion axon regeneration.

    Barbara Lorber

    Full Text Available Axon regeneration in the adult central nervous system (CNS is limited by several factors including a lack of neurotrophic support. Recent studies have shown that glia from the adult rat CNS, specifically retinal astrocytes and Müller glia, can promote regeneration of retinal ganglion cell axons. In the present study we investigated whether retinal glia also exert a growth promoting effect outside the visual system. We found that retinal glial conditioned medium significantly enhanced neurite growth and branching of adult rat dorsal root ganglion neurons (DRG in culture. Furthermore, transplantation of retinal glia significantly enhanced regeneration of DRG axons past the dorsal root entry zone after root crush in adult rats. To identify the factors that mediate the growth promoting effects of retinal glia, mass spectrometric analysis of retinal glial conditioned medium was performed. Apolipoprotein E and secreted protein acidic and rich in cysteine (SPARC were found to be present in high abundance, a finding further confirmed by western blotting. Inhibition of Apolipoprotein E and SPARC significantly reduced the neuritogenic effects of retinal glial conditioned medium on DRG in culture, suggesting that Apolipoprotein E and SPARC are the major mediators of this regenerative response.

  1. EEG functional connectivity, axon delays and white matter disease

    Nunez, Paul L.; Srinivasan, Ramesh; Fields, R. Douglas

    2016-01-01

    Objective Both structural and functional brain connectivities are closely linked to white matter disease. We discuss several such links of potential interest to neurologists, neurosurgeons, radiologists, and non-clinical neuroscientists. Methods Treatment of brains as genuine complex systems suggests major emphasis on the multi-scale nature of brain connectivity and dynamic behavior. Cross-scale interactions of local, regional, and global networks are apparently responsible for much of EEG's oscillatory behaviors. Finite axon propagation speed, often assumed to be infinite in local network models, is central to our conceptual framework. Results Myelin controls axon speed, and the synchrony of impulse traffic between distant cortical regions appears to be critical for optimal mental performance and learning. Results Several experiments suggest that axon conduction speed is plastic, thereby altering the regional and global white matter connections that facilitate binding of remote local networks. Conclusions Combined EEG and high resolution EEG can provide distinct multi-scale estimates of functional connectivity in both healthy and diseased brains with measures like frequency and phase spectra, covariance, and coherence. Significance White matter disease may profoundly disrupt normal EEG coherence patterns, but currently these kinds of studies are rare in scientific labs and essentially missing from clinical environments. PMID:24815984

  2. Dysregulated axonal RNA translation in amyotrophic lateral sclerosis.

    Yasuda, Kyota; Mili, Stavroula

    2016-09-01

    Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease that has been associated with a diverse array of genetic changes. Prominent among these are mutations in RNA-binding proteins (RBPs) or repeat expansions that give rise to toxic RNA species. RBPs are additionally central components of pathologic aggregates that constitute a disease hallmark, suggesting that dysregulation of RNA metabolism underlies disease progression. In the context of neuronal physiology, transport of RNAs and localized RNA translation in axons are fundamental to neuronal survival and function. Several lines of evidence suggest that axonal RNA translation is a central process perturbed by various pathogenic events associated with ALS. Dysregulated translation of specific RNA groups could underlie feedback effects that connect and reinforce disease manifestations. Among such candidates are RNAs encoding proteins involved in the regulation of microtubule dynamics. Further understanding of axonally dysregulated RNA targets and of the feedback mechanisms they induce could provide useful therapeutic insights. WIREs RNA 2016, 7:589-603. doi: 10.1002/wrna.1352 For further resources related to this article, please visit the WIREs website. PMID:27038103

  3. Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis.

    Yuta Iwai

    Full Text Available Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS, suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP amplitude (index of motor neuronal loss and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44, ALS patients (n = 140 had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p 5mV. Regression analyses showed that SDTC (R = -0.22 and depolarizing threshold electrotonus (R = -0.22 increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS.

  4. Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis.

    Iwai, Yuta; Shibuya, Kazumoto; Misawa, Sonoko; Sekiguchi, Yukari; Watanabe, Keisuke; Amino, Hiroshi; Kuwabara, Satoshi

    2016-01-01

    Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS), suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP) amplitude (index of motor neuronal loss) and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44), ALS patients (n = 140) had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p CMAP (> 5mV). Regression analyses showed that SDTC (R = -0.22) and depolarizing threshold electrotonus (R = -0.22) increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS. PMID:27383069

  5. Sensory axon-derived neuregulin-1 is required for axoglial signaling and normal sensory function but not for long-term axon maintenance

    Fricker, F.R.; Zhu, N.; Tsantoulas, C.;

    2009-01-01

    " pockets. The total number of axons in the sural nerve was unchanged, but a greater proportion was unmyelinated. In addition, we observed large-diameter axons that were in a 1:1 relationship with Schwann cells, surrounded by a basal lamina but not myelinated. There was no evidence of DRG or Schwann cell...

  6. Axon Degeneration Gated by Retrograde Activation of Somatic Pro-apoptotic Signaling.

    Simon, David J; Pitts, Jason; Hertz, Nicholas T; Yang, Jing; Yamagishi, Yuya; Olsen, Olav; Tešić Mark, Milica; Molina, Henrik; Tessier-Lavigne, Marc

    2016-02-25

    During development, sensory axons compete for limiting neurotrophic support, and local neurotrophin insufficiency triggers caspase-dependent axon degeneration. The signaling driving axon degeneration upon local deprivation is proposed to reside within axons. Our results instead support a model in which, despite the apoptotic machinery being present in axons, the cell body is an active participant in gating axonal caspase activation and axon degeneration. Loss of trophic support in axons initiates retrograde activation of a somatic pro-apoptotic pathway, which, in turn, is required for distal axon degeneration via an anterograde pro-degenerative factor. At a molecular level, the cell body is the convergence point of two signaling pathways whose integrated action drives upregulation of pro-apoptotic Puma, which, unexpectedly, is confined to the cell body. Puma then overcomes inhibition by pro-survival Bcl-xL and Bcl-w and initiates the anterograde pro-degenerative program, highlighting the role of the cell body as an arbiter of large-scale axon removal. PMID:26898330

  7. Regulation of action potential waveforms by axonal GABAA receptors in cortical pyramidal neurons.

    Yang Xia

    Full Text Available GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb of the main axon trunk of layer -5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors.

  8. Irregular geometries in normal unmyelinated axons: a 3D serial EM analysis.

    Greenberg, M M; Leitao, C; Trogadis, J; Stevens, J K

    1990-12-01

    Axons have generally been represented as straight cylinders. It is not at all uncommon for anatomists to take single cross-sections of an axonal bundle, and from the axonal diameter compute expected conduction velocities. This assumes that each cross-section represents a slice through a perfect cylinder. We have examined the three-dimensional geometry of 98 central and peripheral unmyelinated axons, using computer-assisted serial electron microscopy. These reconstructions reveal that virtually all unmyelinated axons have highly irregular axial shapes consisting of periodic varicosities. The varicosities were, without exception, filled with membranous organelles frequently including mitochondria, and have obligatory volumes similar to that described in other neurites. The mitochondria make contact with microtubules, while the other membraneous organelles were frequently found free floating in the cytoplasm. We conclude that unmyelinated axons are fundamentally varicose structures created by the presence of organelles, and that an axon's calibre is dynamic in both space and time. These irregular axonal geometries raise serious doubts about standard two dimensional morphometric analysis and suggest that electrical properties may be more heterogeneous than expected from single section data. These results also suggest that the total number of microtubules contained in an axon, rather than its single section diameter, may prove to be a more accurate predictor of properties such as conduction velocity. Finally, these results offer an explanation for a number of pathological changes that have been described in unmyelinated axons. PMID:2292722

  9. POEMS Syndrome Diagnosed 10 Years after Disabling Peripheral Neuropathy

    Viet H. Nguyen

    2011-01-01

    Full Text Available Peripheral neuropathy is characterized as a generalized, relatively homogeneous process affecting many peripheral nerves and predominantly affecting distal nerves. The epidemiology of peripheral neuropathy is limited since the disease presents with varying etiology, pathology, and severity. Toxic, inflammatory, hereditary, and infectious factors can cause damage to the peripheral nerves resulting in peripheral neuropathy. Peripheral neuropathy is most commonly caused by diabetes, alcohol, HIV infection, and malignancy. We report a case of a 42-year-old female with 10-year history of progressively worsening peripheral neuropathy, hypothyroidism, and skin changes who presents with dyspnea secondary to recurrent pleural and pericardial effusions. Prior to her arrival, her peripheral neuropathy was believed to be secondary to chronic demyelinating inflammatory polyneuropathy (CDIP given elevated protein in the cerebral spinal fluid (CSF which was treated with intravenous immunoglobulin (IVIG and corticosteroids. Unfortunately, her peripheral neuropathy did not have any improvement. Incidentally, patient was found to have splenomegaly and papilledema on physical exam. Serum protein electrophoresis showed a monoclonal pattern of IgA lambda. Patient met the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome. An underlying diagnosis of POEMS syndrome should be considered in patients with chronic debilitating neuropathy and an elevated protein in the CSF.

  10. Why do we need optic nerve decompression of traumatic optic neuropathy patients?

    Seong Rok Han, M.D., Ph.D.

    2014-01-01

    Traumatic optic neuropathy can be treated by various methods including high-dose steroids and surgical decompression. Neurosurgical decompression could be required in patients with mechanical compression of the optic nerve by displaced orbital roof fracture fragments. We describe two patients of traumatic optic neuropathy due to orbital roof fracture who had improved pupil reflex and visual acuity after decompression of the optic nerve.

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

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

    2015-01-01

    Background & aims: Diabetic peripheral neuropathy (DPN) accounts for most common complications of T2DM. Painful DPN is associated with functional limitation & poor quality of life. Therefore, objective of the study is to find the effect of low level laser therapy on painful diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM)

  12. On the cause of brachial plexus neuropathy after radiation therapy of patients with mamma carcinoma

    Radiation therapy is often considered as cause of brachial plexus neuropathy in patients with mamma carcinoma. One case (in which metastases could be established as specific cause) is used as specific example for the possible differential diagnosis of brachial plexus neuropathy. (orig.)

  13. Noradrenaline and isoproterenol kinetics in diabetic patients with and without autonomic neuropathy

    Dejgaard, Anders; Hilsted, J; Christensen, N J

    1986-01-01

    Noradrenaline and isoproterenol kinetics using intravenous infusion of L-3H-NA and of 3H-isoproterenol were investigated in eight Type 1 (insulin-dependent) diabetic patients without neuropathy and in eight Type 1 diabetic patients with autonomic neuropathy matched for age, sex and duration of di...

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

    Saidha, Shiv

    2010-01-01

    We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them.

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

    Hong-xia Xue

    2015-01-01

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

  16. Soluble axoplasm enriched from injured CNS axons reveals the early modulation of the actin cytoskeleton.

    Patrick Garland

    Full Text Available Axon injury and degeneration is a common consequence of diverse neurological conditions including multiple sclerosis, traumatic brain injury and spinal cord injury. The molecular events underlying axon degeneration are poorly understood. We have developed a novel method to enrich for axoplasm from rodent optic nerve and characterised the early events in Wallerian degeneration using an unbiased proteomics screen. Our detergent-free method draws axoplasm into a dehydrated hydrogel of the polymer poly(2-hydroxyethyl methacrylate, which is then recovered using centrifugation. This technique is able to recover axonal proteins and significantly deplete glial contamination as confirmed by immunoblotting. We have used iTRAQ to compare axoplasm-enriched samples from naïve vs injured optic nerves, which has revealed a pronounced modulation of proteins associated with the actin cytoskeleton. To confirm the modulation of the actin cytoskeleton in injured axons we focused on the RhoA pathway. Western blotting revealed an augmentation of RhoA and phosphorylated cofilin in axoplasm-enriched samples from injured optic nerve. To investigate the localisation of these components of the RhoA pathway in injured axons we transected axons of primary hippocampal neurons in vitro. We observed an early modulation of filamentous actin with a concomitant redistribution of phosphorylated cofilin in injured axons. At later time-points, RhoA is found to accumulate in axonal swellings and also colocalises with filamentous actin. The actin cytoskeleton is a known sensor of cell viability across multiple eukaryotes, and our results suggest a similar role for the actin cytoskeleton following axon injury. In agreement with other reports, our data also highlights the role of the RhoA pathway in axon degeneration. These findings highlight a previously unexplored area of axon biology, which may open novel avenues to prevent axon degeneration. Our method for isolating CNS axoplasm

  17. Therapeutische Überlegungen bei sensomotorischer diabetischer Neuropathie

    Bührlen M

    2013-01-01

    Full Text Available Der Begriff der sensomotorischen diabetischen Neuropathie beschreibt einen heterogenen Beschwerdekomplex, der auf einer diabetesbedingten Schädigung des peripheren Nervensystems beruht. Bis zu 50 % der Menschen mit Diabetes mellitus leiden im Verlauf ihrer Erkrankung an Symptomen einer sensomotorischen Neuropathie. Chronische Schmerzen, Dysund Parästhesien sowie die Komplikation des diabetischen Fußsyndroms stellen für die Betroffenen gravierende Folgen dar. Die Optimierung der metabolischen Kontrolle stellt eine wichtige Basismaßnahme dar. Andere, zweifelsfrei gesicherte Möglichkeiten der Prävention oder kausalen Therapie sind nicht bekannt. Bei Auftreten einer schmerzhaften Neuropathie sollte eine gezielte analgetische Therapie möglichst früh begonnen werden. Mit den trizyklischen Antidepressiva, Duloxetin, Gabapentin und Pregabalin stehen Wirkstoffe zur Verfügung, die eine spezifische Therapie neuropathischer Schmerzen ermöglichen. Dabei ist zu beachten, dass in der Regel keine Schmerzfreiheit erreicht werden kann. Entscheidend ist das Erreichen eines für den Patienten tolerablen Schmerzniveaus unter Minimierung medikamentenassoziierter Nebenwirkungen. Das individuelle Ansprechen auf ein Medikament und die optimale Dosis können nicht vorhergesagt, sondern müssen individuell erprobt werden. Bei leichten Schmerzen können die Nicht-Opioid- Analgetika Paracetamol und Metamizol eingesetzt werden. Fehlen Therapiealternativen, dann stellen Opioide eine weitere Möglichkeit der Therapie starker Schmerzen dar. Aufgrund einer zusätzlichen Monoamin-Wiederaufnahmehemmerwirkung nehmen Tramadol und Tapentadol in dieser Gruppe eine Sonderstellung ein. In der Risiko- Nutzen-Abwägung darf das Nebenwirkungs- und Abhängigkeitspotenzial der Opioide in der Langzeittherapie nicht unterschätzt werden. Für andere medikamentöse Therapien oder alternative Therapiemethoden liegt keine ausreichende wissenschaftliche Evidenz vor. Sie können aber im

  18. Diagnostic imaging of compression neuropathy; Bildgebende Diagnostik von Nervenkompressionssyndromen

    Weishaupt, D.; Andreisek, G. [Universitaetsspital, Institut fuer Diagnostische Radiologie, Zuerich (Switzerland)

    2007-03-15

    Compression-induced neuropathy of peripheral nerves can cause severe pain of the foot and ankle. Early diagnosis is important to institute prompt treatment and to minimize potential injury. Although clinical examination combined with electrophysiological studies remain the cornerstone of the diagnostic work-up, in certain cases, imaging may provide key information with regard to the exact anatomic location of the lesion or aid in narrowing the differential diagnosis. In other patients with peripheral neuropathies of the foot and ankle, imaging may establish the etiology of the condition and provide information crucial for management and/or surgical planning. MR imaging and ultrasound provide direct visualization of the nerve and surrounding abnormalities. Bony abnormalities contributing to nerve compression are best assessed by radiographs and CT. Knowledge of the anatomy, the etiology, typical clinical findings, and imaging features of peripheral neuropathies affecting the peripheral nerves of the foot and ankle will allow for a more confident diagnosis. (orig.) [German] Kompressionsbedingte Schaedigungen peripherer Nerven koennen die Ursache hartnaeckiger Schmerzen im Bereich des Sprunggelenks und Fusses sein. Eine fruehzeitige Diagnose ist entscheidend, um den Patienten der richtigen Therapie zuzufuehren und potenzielle Schaedigungen zu vermeiden oder zu verringern. Obschon die klinische Untersuchung und die elektrophysiologische Abklaerungen die wichtigsten Elemente der Diagnostik peripherer Nervenkompressionssyndrome sind, kann die Bildgebung entscheidend sein, wenn es darum geht, die Hoehe des Nervenschadens festzulegen oder die Differenzialdiagnose einzugrenzen. In gewissen Faellen kann durch Bildgebung sogar die Ursache der Nervenkompression gefunden werden. In anderen Faellen ist die Bildgebung wichtig bei der Therapieplanung, insbesondere dann, wenn die Laesion chirurgisch angegangen wird. Magnetresonanztomographie (MRT) und Sonographie ermoeglichen eine

  19. Diagnostic ability of Barrett's index to detect dysthyroid optic neuropathy using multidetector computed tomography

    Objectives: The objective of this study was to evaluate the ability of a muscular index (Barrett's Index), calculated with multidetector computed tomography, to detect dysthyroid optic neuropathy in patients with Graves' orbitopathy. Methods: Thirty-six patients with Graves' orbitopathy were prospectively studied and submitted to neuro-ophthalmic evaluation and multidetector computed tomography scans of the orbits. Orbits were divided into two groups: those with and without dysthyroid optic neuropathy. Barrett's index was calculated as the percentage of the orbit occupied by muscles. Sensitivity and specificity were determined for several index values. Results: Sixty-four orbits (19 with and 45 without dysthyroid optic neuropathy) met the inclusion criteria for the study. The mean Barrett's index values (±SD) were 64.47% ± 6.06% and 49.44% ± 10.94% in the groups with and without dysthyroid optic neuropathy, respectively (p60% should be carefully examined and followed for the development of dysthyroid optic neuropathy. (author)

  20. Computer use and ulnar neuropathy: results from a case-referent study

    Andersen, JH; Frost, P.; Fuglsang-Frederiksen, A.;

    2012-01-01

    performed by conditional logistic regression.There were a negative association between daily hours of computer use and the two outcomes of interest. Participants who reported their elbow to be in contact with their working table for 2 hours or more during the workday had an elevated risk for ulnar......We aimed to evaluate associations between vocational computer use and 1) ulnar neuropathy, and 2) ulnar neuropathy- like symptoms as distinguished by electroneurography. We identified all patients aged 18-65 years, examined at the Department of Neurophysiology on suspicion of ulnar neuropathy, 2001......-2007. We mailed a questionnaire to 546 patients with ulnar neuropathy, 633 patients with ulnar neuropathy-like symptoms, and three community referents per case, matched on sex, age, and primary care centre. From a Job Exposure Matrix we extracted estimates of daily hours of computer use. The analysis was...