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Peripheral Neuropathy (peripheral + neuropathy)
Kinds of Peripheral Neuropathy Selected AbstractsA MOUSE MODEL FOR PERIPHERAL NEUROPATHY PRODUCED BY A PARTIAL INJURY OF THE NERVE SUPPLYING THE TAILJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2002SK Back We attempted to develop a mouse model for peripheral neuropathy by a partial injury of the nerve supplying the tail. Under enflurane anesthesia, the unilateral superior caudal trunk was resected between the S3 and S4 spinal nerves. Tests for thermal allodynia were conducted by immersing the tail into 4 or 38°C water. The mechanical allodynia was assessed by stimulating the tail with a von Frey hair (1.96 mN, 0.2 g). After the nerve injury, the experimental animals had shorter tail withdrawal latencies to cold and warm water immersion than the presurgical latency, and exhibited an increase in tail response to von Frey stimulation. We interpret these abnormal sensitivities as the signs of mechanical, cold and warm allodynia following the superior caudal trunk injury in the mouse. [source] Peripheral Neuropathy in Acrodermatitis Chronica Atrophicans , Effect of TreatmentJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2003E Kindstrand Forty-seven patients with the late borrelial manifestation acrodermatitis chronica atrophicans (ACA) and with objective neurological and/or neurophysiological findings were followed up after antibiotic treatment with dermatological, serological, neurological and neurophysiological controls. Despite a good therapeutic effect on ACA lesions, specific antibody values and symptoms of irritative nerve lesions, the objective neurological and neurophysiological findings of nerve deficit remained unchanged. There was no progress of neuropathy findings during the follow-up time. Our interpretation of the results is that the remaining neuropathy signs after treatment of ACA are neurological sequelae and not manifestations of persisting Borrelia infection. [source] HCV-RNA In Sural Nerve From Hcv Infected Patients With Peripheral NeuropathyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001L De Martino Objective: Evaluation of hepatitis C virus (HCV) by reverse transcription-polymerase chain reaction (RT-PCR) in peripheral nerve tissues from HCV infected patients with peripheral neuropathy. METHODS: RT-PCR was performed on homogenates of nerve biopsies from 17 consecutive HCV-positive patients with peripheral neuropathy, with or without mixed cryoglobulinemia, hospitalised from 1996 to 2000. Sural nerve specimens were frozen in iso-pentane pre-cooled in liquid nitrogen and stored at ,80°C until use. RNA was extracted from ten 7-,m thick cryostatic sections or from a nerve trunk specimen of about 3 mm length, collected from each biopsy. Three different protocols of RNA extraction were tested (1,3). Complementary DNAs (cDNAs) were obtained without or with RNasin (Promega, Madison, WI) addition in the reaction mixture to inhibit residual RNase activity. Two sets of commercially available PCR primers for the outer and the nested reaction were used. PCR products were analysed by agarose gel electrophoresis and ethidium bromide staining. Serum samples and liver specimens from proven HCV positive patients served as positive controls, whereas sera from healthy subjects were negative controls. RESULTS: Sufficient amount of RNA could be obtained either by cryostatic sections or by in toto nerve specimens. Extraction by Trizol (Gibco-BRL) allowed the best concentration and purity of RNA as assessed by biophotometry. The presence of RNasin didn't improve the cDNA synthesis. The resulting amplification product of the nested PCR was 187 bp long. We have always observed this product in our positive controls and never in the negative. Six samples from patients either with or without cryoglobulinemia resulted positive; 7 were negative. Four samples gave variable results. CONCLUSIONS: While 40% of the nerves in our series were undoubtedly HCV positive, the cause(s) of negative and variable results in the remaining samples is likely more complex than variations in the detection protocols and deserve further investigations. REFERENCES: 1) Chomczynski P, Sacchi N (1987). Anal Biochem 162:156. 2) Marquardt O et al. (1996). Med Microbiol Lett 5:55. 3) Chomczynski P (1993). Bio/Techniques 15:532. [source] Bilateral occipital neuropathy as a rare complication of positioning for thyroid surgery in a morbidly obese patientACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2004S. Schulz-Stübner Background:, Peripheral neuropathies in various locations are described as complications after anesthesia and surgery. This is the first case report of temporary bilateral occipital neuropathy from positioning for thyroid surgery in a morbidly obese patient. Methods:, A 48-year-old women with a history of depression, fibro-myalgia, asthma, sleep apnea, diabetes mellitus and morbid obesity (127 kg, 165 cm) underwent 4 hours anesthesia with propofol/remifentanil without muscle relaxation for thyroid surgery. The neck with a very low range of motion secondary to fat tissue needed to be extended to facilitate surgery as much as possible. The head was carefully padded and there were no episodes of hypotension or hypoxemia throughout the case or in the PACU. At post op day 1 she complained of bilateral numbness in the distribution area of both greater occipital nerves. On post op day 2 tingling sensations and improvement of numbness was noticed. The patient recovered without residual symptoms after 6 weeks. Conclusion:, Pressure or shear stress to the nerve, hypoperfusion or metabolic disturbances are discussed as the leading etiology of nerve damage during surgery in the literature. Pressure from fat tissue during prolonged head extension for surgery seems to be the cause in this case and should therefore be avoided whenever possible in morbidly obese patients, especially when other risk factors for neuropathy like diabetes are present. [source] The neurology and neuropathology of coeliac diseaseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2000A. J. Wills A number of neurological syndromes have been described in association with coeliac disease. These include disorders of the central nervous system encompassing epilepsy, myoclonus, ataxia, internuclear opthalmoplegia, multifocal leukoencephalopathy and dementia. Most of these associated conditions show a poor response to gluten restriction. Peripheral neuropathies, of axonal and demyelinating types, have also been reported and may respond to elimination of gluten from the diet. The mechanism underlying these processes remains obscure but may be immunological or related to trace vitamin deficiencies. Controversially, it has also been claimed that occult coeliac disease accounts for a substantial proportion of patients with neurological dysfunction of unknown cause. Some authorities recommend that cryptogenic ataxias and neuropathies should be routinely screened for the presence of gluten-sensitivity but this remains contentious and has not been universally accepted. This review will attempt to review the clinical and pathological findings in this condition and speculate on pathogenesis and directions for future research. [source] Peripheral neuropathy: a practical approach to diagnosis and managementEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2001K. A. Jellinger No abstract is available for this article. [source] Peripheral neuropathy associated with common variable immunodeficiencyEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2000A. J. Larner We report a patient with common variable immunodeficiency (CVID) who developed an axonal sensorimotor polyneuropathy, a hitherto unreported association to our knowledge. These conditions may be linked at the pathogenetic level, since some CVID patients are prone to the development of autoimmune disease. [source] Peripheral neuropathy with infliximab therapy in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 12 2009D.C. Burger MD, MBBS (Hons) No abstract is available for this article. [source] Peripheral neuropathy associated with topical tretinoin therapyINTERNAL MEDICINE JOURNAL, Issue 12 2009I. Marie No abstract is available for this article. [source] PDE5 inhibitors in diabetic peripheral neuropathyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2006G. HACKETT Summary Peripheral neuropathy is the most common complication of diabetes. This paper reviews the case histories of five patients with diabetic peripheral neuropathy or severe peripheral vascular disease who reported improvement in their symptoms when treated with regular or daily dosing with phosphodiesterase type 5 inhibitors (PDE5Is). These patients had been previously treated with PDE5Is for erectile dysfunction (ED) and not responded to on-demand therapy with a PDE5I at maximal recommended dose. This improvement is likely to be due to the known benefit of these drugs on endothelial dysfunction via an improvement of blood supply to the vasa nervorum. These cases suggest that further research is indicated to evaluate the potential use of PDE5Is in the treatment and prevention of diabetic peripheral neuropathy, particularly as these drugs are already licensed to treat ED, which occurs in around 50% of male diabetics. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 73JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003C Inglese Cryoglobulinemic neuropathy is probably the commonest form of vasculitic neuropathy in Mediterranean countries, as usually related to the widespread hepatitis C virus (HCV) infection. We describe the spectrum of manifestations in a large series of patients with cryoglobulinemic neuropathy, also analyzing the impact of comorbid factors, which are quite frequent in HCV-related mixed cryoglobulinemia. The cohort included 60 patients (10 men, 50 women) with peripheral neuropathy associated with mixed cryoglobulinemia as main or sole cause (type 2 in 36 cases, type 3 in 4, not typized in 20), HCV-related in all patients but 8 (3 men and 5 women). Median age of patients was 65 years (range 41,85), and median age at onset of neuropathy was 59 (range 40,84). Peripheral neuropathy represented an onset manifestation of mixed cryoglobulinemia in about half patients. The most frequent clinical pattern was pure sensory neuropathy in 40 patients, including 4 patients with prominent ataxia; sensory neuropathy was asymmetrical in distribution in 9 patients, and in 14 patients sensory action potentials (SAPs) of the sural nerve were normal, suggesting selective involvement of the small sensory fibers. The remaining patients had sensorimotor neuropathy (15 cases) and mononeuropathy multiplex (5 cases). Positive sensory symptoms and restless legs syndrome were the most common manifestations. Neurophysiological study showed axonal degeneration of varying severity in all patients. In 20 patients, additional causes of neuropathy were present, including type 2 diabetes (5 patients), glucose intolerance (6 patients), non-Hodgkin lymphoma (3 patients), and alcohol (2 patients). With respect with this subset of patients, in "pure" cryoglobulinemic neuropathy there was more often a pattern of sensory neuropathy (31/40 vs. 6/20; p = 0.001), with more frequent asymmetrical distribution (9 vs 0; p = 0.05) and small fiber involvement (11 vs 3). Severity of neuropathy, as judged on the basis of the Rankin scale and of neurophysiological changes, was similar in the two subgroups. Our study confirms that sensory neuropathy, often asymmetrical, is the most common clinical pattern in cryoglobulinemic neuropathy, and is consistently present in pure cryoglobulinemic neuropathy rather than in patients with other associated causes of neuropathy; in these latter, paradoxically, clinical and neurophysiological impairment seems not greater than in pure cryoglobulinemic neuropathy. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 79JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003U Del Carro Peripheral neuropathy is one of the most common secondary complications of diabetes mellitus, causing severe and prolonged morbidity. However, clinical and experimental studies have reported that careful glucose control may prevent, stabilize, and/or reverse neuropathy and other chronic diabetic complications. Unfortunately, insulin therapy does not prevent the development or progression of chronic lesions in the vessels, kidneys, eyes, or nerves of the diabetic patient. There is great interest in investigating other forms of endocrine replacement therapy, such as transplantation of the pancreas or of the islets of Langerhans (IT). Diabetic polyneuropathy (DP) evolution is characterized by progressive demyelination and axonal loss and is manifested by signs and symptoms on physical examination and abnormalities in nerve conduction studies (NCS). NCS provide reliable, noninvasive, objective measures of peripheral nerve function and constitute the most important technique for the evaluation of the severity of DP in clinical trials. Several research groups have demonstrated that skin biopsy with measurement of intraepidermal nerve fiber density is another method minimally invasive and repeatable that provides direct pathologic evidence of axonal damage in diabetic neuropathy. Fifty-one consecutive IDDM patients with or without end stage renal disease were enrolled at the moment of islet (Is), kidney (KD), kidney-pancreas (KP) or kidney-islet (KI) transplantation. Patients underwent skin biopsy punch, neurologic examination and neurophysiological investigation. Particularly, 20 pts underwent KP tx, 16 KD tx, 10 islet tx and 5 KI. The patients were comparable for duration of diabetes, dialysis (when present), age, lipid profile. In half of the patients a follow-up of 2 years has been reached. After KP tx, and partially with KI, a complete normalization of glycometabolic control has been achieved, with statistically lower HbA1c in comparison with KD group (KP = 6.2; 0.1% vs. KD = 8.4; 0.5%; p < 0.01). In the KI/Is group, a long-term restoration of islet endocrine function has been achieved, with insulin independence. When this has been lost, a persistent secretion of C-peptide was shown for a long period of time. This was correlated with a global improvement quality of life and vascular structure. Preliminary results will be presented. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 81JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003S Lori Symptomatic neuropathy in young patients with type 1 Diabetes Mellitus (t1DM) is rare but subclinical peripheral alterations can be assessed by electroclinical evaluation. This study aimed to assess prevalence of clinical and subclinical peripheral neuropathy in patients with t1DM. Motor and/or sensory nerve conduction studies of both median, ulnar, peroneal, tibial and sural nerves and standard clinical examination of peripheral nervous system were performed in 83 patients (27 females and 56 males) with diabetes onset since five years. The mean age of patients was 19.89 (range 9,28.3) years, the mean disease duration was 9.61(range 4.4,19.3) and the mean age at the onset of diabetes was 9.02 (range 0.8,23.5). Five patients (6.02 %) had both symptomatic (light clinical abnormalities as paresthesias and mild reduction of vibratory sensibility) and electrophysiologic neuropathy and six (7.2 %) with mild abnormal nerve conduction studies were totally asymptomatic (subclinical neuropathy). The majority of symptoms and electrophysiological alterations were found on the lower limbs. Only two patients had a minimal distal neuropathy of median nerve. No patients showed laboratory evidence of early renal complications or systemic hypertension; 5 (6.02 %) had early diabetic retinal abnormalities as microaneurisms, seen by fundus examination. Analysis of sex, age of onset, duration of diabetes, age at the date of electrophysiologic examination, Hemoglobin A1c (mean level of the last two years), association with retinal abnormalities and clinical assessment was performed (Fisher Exact Test, ANOVA). No correlation was found with the age at the onset, retinal abnormalities and glycaemic control index. Peripheral neuropathy was significantly related with patient age at the date of electrophysiological study and duration of t1DM. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 62JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003C Briani Thalidomide seems to be effective in the treatment of cutaneous forms of lupus erythematosus refractory to other therapies. Peripheral neuropathy is the most severe side effect, but the incidence of neuropathy and its relation to thalidomide doses are still unclear. We prospectively monitored 12 patients treated with thalidomide for cutaneous lupus erythematosus in order to estimate the occurrence of side effects, particularly peripheral neuropathy. A total of 12 female patients, median age 38,6 years (range 26,56), with subacute or chronic cutaneous lupus erythematosus were considered. The patients were treated with low dose thalidomide (starting dose 100 mg, tapered to 50 mg/day or 50 mg alternative day) for up to 18 months. The average follow-up period was 8,6 months (range 2,18). Prior to, and regularly during treatment patients underwent neurological evaluation and electrophysiological study of at least 8 nerves in the 4 arms (ulnar, median, sural, peroneal nerves). At recruitment, one patient presented a sensory-motor peripheral neuropathy. Of the remaining 11 patients, six did not present electrophysiological evidence of neuropathy, one had a carpal tunnel syndrome and four showed slowing of ulnar nerve velocity at elbow. No patients developed neuropathy neither worsening of electrophysiological parameters during thalidomide treatment. The most common side effect was tremor, always reversible after withdrawing or reducing thalidomide. Paresthesias, somnolence, amenhorrea, constipation were also present. Only one patient had to stop the therapy for the occurrence, 10 days after taking 50 mg of thalidomide, of a severe, stabbing, "zoster-like" thoracic pain, which disappeared upon withdrawal of the drug. Started again on thalidomide, the symptoms reappeared and the patient definitely interrupted the therapy with benefit. All the 11 patients who continued on the therapy presented a significant improvement or remission of the cutaneous alterations. These preliminary data seem to indicate that low dose thalidomide is efficacious and tolerable for cutaneous lupus erythematosus. Peripheral neuropathy seems not to be a major side effect. A longer follow-up and the study of more patients are needed to confirm the results. [source] Peripheral neuropathy associated with mitochondrial disorders: 8 cases and review of the literatureJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2002S. Bouillot Abstract Forty-three cases of peripheral neuropathy (PN) have been reported in the literature with a proven mitochondria (mt) DNA mutation, and 21 had a peripheral nerve biopsy (PNB). We studied 8 patients, 1 of whom had severe sensory PN, 3 mild PN, and 4 subclinical PN. Nerve biopsy was performed in every case; all patients showed axonal degeneration and 4 showed features of primary myelin damage. In addition, there were 2 crystalline-like inclusions in the Schwann cell cytoplasm of a patient with MERRF, and 1 in a patient with multiple deletions on the mtDNA. There are 11 cases of PNB in the literature with axonal lesions, 5 with demyelination, and 4 with mixed lesions. One PNB was not modified. A few crystalline-like inclusions were seen in 1 case of MERRF. Such inclusions were first reported in the Schwann cell cytoplasm of unmyelinated fibers in a patient with Refsum disease and were considered to be modified mitochondria. However, their mitochondrial origin remains debatable. [source] Peripheral neuropathy in an outpatient cohort of patients with Sjögren's syndromeMUSCLE AND NERVE, Issue 5 2006Glenn Lopate MD Abstract Peripheral neuropathy is common in patients with Sjögren's syndrome (SS), but its precise prevalence is unknown. Most prior studies were conducted at neurology or rheumatology specialty clinics and likely selected for a more severely affected population. We evaluated 22 SS patients and 10 controls for evidence of neuropathy in an outpatient setting at a regional meeting of the Sjögren's Syndrome Foundation. We performed neurological examinations and nerve conduction studies (NCSs) and measured serum antinuclear antibody (ANA) and SS-A and SS-B antibody levels. Participants filled out a questionnaire pertaining to symptoms, diagnosis, and treatment. We found that signs and symptoms related to small axons were more common in patients with SS than in controls. Complaints of painful distal paresthesias in the feet were noted in 59% of patients but in only 10% of controls, and of abnormal sweating in 41% and 0%, respectively. Examination revealed decreased pinprick sensation in 64% of patients with SS, but in only 30% of controls. Overall, 45% of the patients but none of the controls were thought to have an isolated small-fiber neuropathy. Large-fiber dysfunction (as measured by testing vibration, deep tendon reflexes, and NCSs) was similar between the two groups. We conclude that small-fiber neuropathy is common in patients with SS. Muscle Nerve 2006 [source] Peripheral neuropathy associated with leflunomide: is there a risk patient profile?,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2007Karin Martin pharmD Abstract Purpose (i) To monitor the potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice and (ii) to describe the characteristics of patients presenting with this peripheral nervous system symptoms. Method All patients treated with leflunomide between May 2000 and April 2003 and followed in the rheumatology department of the University Hospital participated in the study. Data concerning treatment patterns with leflunomide, demographic and disease characteristics were obtained from clinical charts. Neuropathy was diagnosed with nerve conduction study (NCS). Cases of neuropathy were described and then compared to other patients using univariate analyses. Results One hundred and thirteen patients were included in the study. M/F sex ratio was 0.45. Mean age at start of treatment was 55.6 years (range,=,27,81). During the study period, eight incident cases of peripheral neuropathy and two cases of worsening of preexisting neuropathy were reported (incidence: 9.8%). Compared with other patients, neuropathy cases were older (69 vs. 54 years, p,=,0.0006), more often diabetic (30% vs. 2.9%, p,=,0.009) and more often treated with potentially neurotoxic drugs (20% vs. 1.9%, p,=,0.039). At least one risk factor (potentially neurotoxic drug or diabetes) was found in 50% of patients with neuropathy versus 4% of patients without neuropathy (56% PPV, 96% NPV). Conclusion Cases of toxic neuropathy have been observed during treatment of rheumatoid arthritis with leflunomide. Their occurrence seems to be associated with known risk factors. Careful monitoring of the patient's neurological status during leflunomide treatment is therefore mandatory. Copyright © 2006 John Wiley & Sons, Ltd. [source] Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson diseaseANNALS OF NEUROLOGY, Issue 1 2010Cory Toth MD Objective Peripheral neuropathy (PN) is thought to be coincidental in patients with idiopathic Parkinson disease (IPD). We sought to examine the prevalence of PN in a population of IPD patients and a potential relationship to levodopa use and fasting methylmalonic acid (MMA) levels. Methods In a prospective cohort study, IPD patients randomly selected from a comprehensive database were compared to control subjects regarding the presence and severity of PN using clinical and electrophysiological measures. IPD severity was determined using the Unified Parkinson's Disease Rating Scale (UPDRS). We determined the relation of levodopa use with serum levels of cobalamin, MMA, and homocysteine (Hcy). We also explored the association between presence and severity of PN and age, duration of IPD, cumulative levodopa dosing, cobalamin, MMA, and Hcy levels. Results Fifty-eight randomly selected IPD patients were compared to 58 age- and sex-matched controls. PN was present in 55% of IPD patients and 9% of controls. Patients with IPD had greater prevalence of PN and fasting MMA/Hcy levels than controls. IPD patients with PN were older and exhibited higher UPDRS scores, fasting MMA/Hcy levels, and cumulative levodopa exposure. PN severity in IPD subjects positively correlated with both levodopa exposure and MMA levels. Interpretation IPD patients have a higher prevalence of PN than controls. Although causality is not established, levodopa exposure is associated with MMA elevation and sensorimotor neuropathy in IPD patients. Cobalamin replacement concurrent with levodopa therapy should be considered to protect against development of PN in IPD patients. ANN NEUROL 2010;67:28,36 [source] ,2 -adrenoceptors are critical for antidepressant treatment of neuropathic pain,ANNALS OF NEUROLOGY, Issue 2 2009Ipek Yalcin PharmD Objective Tricyclic antidepressants (TCAs) are one of the first-line pharmacological treatments against neuropathic pain. TCAs increase the extracellular concentrations of noradrenaline and serotonin by blocking the reuptake transporters of these amines. However, the precise downstream mechanism leading to the therapeutic action remains identified. In this work, we evaluated the role of adrenergic receptors (ARs) in the action of TCAs. Methods We used pharmacological and genetic approaches in mice to study the role of ARs in the antiallodynic action of the TCA nortriptyline. Peripheral neuropathy was induced by the insertion of a polyethylene cuff around the main branch of the sciatic nerve. The specific role of ,2 -AR was evaluated by studying ,2 -AR,/, mice. We used von Frey filaments to assess mechanical allodynia. Results The antiallodynic action of nortriptyline was not affected by cotreatment with the ,2 -AR antagonist yohimbine, the ,1 -AR antagonists atenolol or metoprolol, or the ,3 -AR antagonist SR 59230A. On the contrary, the ,-AR antagonists propranolol or sotalol, the ,1/,2 -AR antagonists alprenolol or pindolol, or the specific ,2 -AR antagonist ICI 118,551 blocked the action of nortriptyline. The effect of nortriptyline was also totally absent in ,2 -AR,deficient mice. Interpretation Stimulation of ,2 -AR is necessary for nortriptyline to exert its antiallodynic action against neuropathic pain. These findings provide new insight into the mechanism by which antidepressants alleviate neuropathic pain. Our results also raise the question of a potential incompatibility between ,-blockers that affect ,2 -AR and antidepressant drugs in patients treated for neuropathic pain. Ann Neurol 2009;65:218,225 [source] Peripheral neuropathy as the first manifestation of Madelung's diseaseBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2000E. Saiz Hervás No abstract is available for this article. [source] High prevalence of neuropathies in patients with end-stage liver diseaseACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010D. Cocito Cocito D, Maule S, Paolasso I, Castelli L, Ciaramitaro P, Poglio F, Ottobrelli A, Grimaldi S. High prevalence of neuropathies in patients with end-stage liver disease. Acta Neurol Scand: 2010: 122: 36,40. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, Peripheral neuropathy has been reported in association with end-stage liver disease, but there is only a limited number of reports on the incidence and features of these neuropathies. Materials and methods,,, In this study, 83 patients awaiting liver transplantation were evaluated for the presence of peripheral and autonomic neuropathy. Results,,, Sixty-five percent of the patients had evidence of neuropathy, in agreement with peripheral NCS or cardiovascular autonomic function test. The neuropathy was more frequent in patients with advanced hepatic failure, evaluated with the MELD score. The most frequent abnormalities in nerve conduction studies were sensory-motor neuropathies and sensory neuropathies, with a length-dependent pattern. Conclusion,,, Peripheral neuropathy and autonomic neuropathy are common in patients with end-stage liver disease with different etiology and correlate with the severity of the liver disease. [source] Lead toxicosis in the horse: A reviewEQUINE VETERINARY EDUCATION, Issue 10 2010B. Puschner Summary Lead intoxication is rarely diagnosed in horses and can present a major challenge to the equine practitioner because of the variety of clinical signs. Horses with lead poisoning can develop gastrointestinal disturbances, neurological abnormalities, haematological changes, or nonspecific signs of weight loss, weakness and rough hair coat, which makes early diagnosis difficult. Fortunately, lead analysis of whole blood is routinely available and can confirm intoxication. Because of the well-described lead-induced peripheral neuropathies in horses, a thorough neurological examination is essential in the investigation of a suspect case. Once diagnosed, the source of lead has to be identified and further exposure prevented. Intoxication can be treated by administering chelating drugs and providing symptomatic and supportive care. [source] Increase of MCP-1 (CCL2) in myelin mutant Schwann cells is mediated by MEK-ERK signaling pathwayGLIA, Issue 8 2008Stefan Fischer Abstract Macrophages are critically involved in the pathogenesis of genetically caused demyelination, as it occurs in inherited demyelinating neuropathies. On the basis of the observation that upregulation of the Schwann cell-derived chemokine MCP-1 (CCL2) is a pathologically relevant mechanism for macrophage activation in mice heterozygously deficient for the myelin component P0 (P0+/,), we posed the question of the intracellular signaling cascade involved. By using western blot analysis of peripheral nerve lysates the MAP-kinases extracellular signal-regulated kinase 1/2 (ERK1/2) and MAP kinase/ERK kinase 1/2 (MEK1/2) showed an early and constantly increasing activation in P0 mutants. Furthermore, in nerve fibers from the P0+/, mutants, Schwann cell nuclei were much more often positive for phosphorylated ERK1/2 than in nerve fibers from wild type mice. In vitro experiments using the MEK1/2-inhibitor CI-1040 decreased ERK1/2-phosphorylation and MCP-1 expression in a Schwann cell-derived cell line. Finally, systemic application of CI-1040 lead to a decreased ERK1/2-phosphorylation and substantially reduced MCP-1-production in peripheral nerves of P0+/, mutant mice. Our study identifies MEK1/2-ERK1/2 signaling as an important intracellular pathway that connects the Schwann cell mutation with the activation of pathogenetically relevant macrophages in the peripheral nerves. These findings may have important implications for the treatment of inherited peripheral neuropathies in humans. © 2008 Wiley-Liss, Inc. [source] Therapeutic plasma exchange: A paired comparison of Fresenius AS104 vs.JOURNAL OF CLINICAL APHERESIS, Issue 2 2001COBE Spectra Abstract For therapeutic plasma exchange (TPE), continuous flow separators are known to be efficient as exemplified by Fresenius AS104 and COBE Spectra. The AS104 uses an interface monitoring system in the centrifuge during TPE, whereas Spectra uses computer algorithms to establish the plasma-cell interface. To determine the plasma collection efficiency (PLCE), anticoagulant (AC) volumes used, and platelets (PLT) lost of the AS104 and the Spectra, we performed a prospective paired comparison of 20 TPE (each machine). The study included 17 patients, 1.3 plasma volume exchanges (without AC), equal inlet rates, and AC ratio of 13:1. Processing times did not include reinfuse mode. Platelet loss was determined by sampling the collection bags. Inlet rates were between 60,110 ml/min. Diagnosis included peripheral neuropathies, TTP and cryoglobulinemia. The AS104 had significantly (P<0.0001) lower average whole blood processed (F:6,601 vs. S:8,584 ml), AC volume (F:532 vs. S:719 ml), and processing time (F:80 vs. S:102 minutes) than Spectra. The AS104 had significantly (P<0.0001) higher average plasma flow rates (F:53 vs. S:44 ml/minute), plasma collection efficiency (F:90 vs. S:69%), and platelet loss (F:2.0 vs. S:0.14 × 1011 plt) than Spectra. Platelet loss correlated with inlet flow rate with the AS104 but not with the Spectra. The AS104 has a significantly higher collection efficiency than Spectra allowing it to remove the same amount of plasma in significantly less time, by processing significantly less blood, using significantly less AC, but removing significantly more platelets than Spectra. J. Clin. Apheresis. 16:61,66, 2001. © 2001 Wiley-Liss, Inc. [source] Workshop 5: NAAG and NAALADase: Functional Properties in the Central and Peripheral Nervous SystemJOURNAL OF NEUROCHEMISTRY, Issue 2002D. Bacich Glutamate carboxypeptidase II (GCPII, also known as N-acetylated-alpha-linked acidic dipeptidase or NAALADase) knockout (KO) mice were generated by inserting a GCPII targeting cassette containing a PGK-Neo resistance marker and stop codons in exons 1 and 2, and removal of exons 1 and 2 intron/exon boundary sequence. Embryonic stem cells were injected into C57BL6 blastocysts, and chimeric offspring born. Germline transmission was confirmed by mating the chimeras to generate heterozygous KO mice. Crossing heterozygous mice generated F2 generation mice homozygous for the null mutant, as confirmed by loss of GCPII protein. NAAG hydrolyzing activity was minimal (0.07 pmol/mg/min) in KO tissue, with normal levels (4.82 pmol/mg/min) in wild types and intermediate levels (1.73 pmol/mg/min) in heterozygotes. Preliminary neuropathy experiments showed KO mice are less affected by nerve-crush and recover faster from the damage-induced neuropathy, as indicated by EMG recording and nerve morphology. Similarly, GCPII KO mice subjected to high dose vitamin B6 displayed less severe neuropathy than wild types, as indicated by reduced sensory nerve conduction velocity and morphological deficits. Also, in a transient middle cerebral artery occlusion model, GCPII KO mice were significantly more resistant to the effects of cerebral ischemia than their wildtype littermates. Findings support GCPII involvement in stroke and in mediating chronic neuropathic conditions and suggest GCPII inhibitors may be useful in treatment of brain ischemia as well as peripheral neuropathies. [source] Developmental abnormalities in the nerves of peripheral myelin protein 22-deficient miceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2007Stephanie A. Amici Abstract Peripheral myelin protein 22 (PMP22) is a tetraspan glycoprotein whose misexpression is associated with a family of hereditary peripheral neuropathies. In a recent report, we have characterized a novel PMP22-deficient mouse model in which the first two coding exons were replaced by the lacZ reporter. To investigate further the myelin abnormalities in the absence of PMP22, sciatic nerves and dorsal root ganglion (DRG) neuron explant cultures from PMP22-deficient mice were studied at various stages of myelination. Throughout the first 3 months of postnatal development, myelin protein and ,4 integrin levels are dramatically reduced, whereas p75 and ,1 integrin remain elevated. By immunostaining, the distributions of several glial proteins, including ,4 integrin, the voltage-gated potassium channel Kv1.1, and E-cadherin, are altered. Schwann cells from PMP22-deficient mice are able to produce limited amounts of myelin in DRG explant cultures, yet the internodal segments are dramatically fewer and shorter. The comparison of PMP22-deficient mice with other PMP22 mutant models reveals that the decrease in ,4 integrin is specific to an absence of PMP22. Furthermore, whereas lysosome-associated membrane protein 1 and ubiquitin are notably up-regulated in nerves of PMP22-deficient mice, heat shock protein 70 levels remain constant or decrease compared with wild-type or PMP22 mutant samples. Together these results support a role for PMP22 in the early events of peripheral nerve myelination. Additionally, although myelin abnormalities are a commonality among PMP22 neuropathic models, the underlying subcellular mechanisms are distinct and depend on the specific genetic abnormality. © 2006 Wiley-Liss, Inc. [source] Molecular alterations resulting from frameshift mutations in peripheral myelin protein 22: Implications for neuropathy severityJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005J.S. Johnson Abstract Alterations in peripheral myelin protein 22 (PMP22) expression are associated with a heterogeneous group of hereditary demyelinating peripheral neuropathies. Two mutations at glycine 94, a single guanine insertion or deletion in PMP22, result in different reading frameshifts and, consequently, an extended G94fsX222 or a truncated G94fsX110 protein, respectively. Both of these autosomal dominant mutations alter the second half of PMP22 and yet are linked to clinical phenotypes with distinct severities. The G94fsX222 is associated with hereditary neuropathy with liability to pressure palsies, whereas G94fsX110 causes severe neuropathy diagnosed as Dejerine-Sottas disease or Charcot-Marie-Tooth disease type IA. To investigate the subcellular changes associated with the G94 frameshift mutations, we expressed epitope-tagged forms in primary rat Schwann cells. Biochemical and immunolabeling studies indicate that, unlike the wild-type protein, which is targeted for the plasma membrane, frameshift PMP22s are retained in the cell, prior to reaching the medial Golgi compartment. Similar to Wt-PMP22, both frameshift mutants are targeted for proteasomal degradation and accumulate in detergent-insoluble, ubiquitin-containing aggregates upon inhibition of this pathway. The extended frameshift PMP22 shows the ability to form spontaneous aggregates in the absence of proteasome inhibition. On the other hand, Schwann cells expressing the truncated protein proliferate at a significantly higher rate than Schwann cells expressing the wild-type or the extended PMP22. In summary, these results suggest that a greater potential for PMP22 aggregation is associated with a less severe phenotype, whereas dysregulation of Schwann cell proliferation is linked to severe neuropathy. © 2005 Wiley-Liss, Inc. [source] Emerging role of mitogen-activated protein kinases in peripheral neuropathiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2007Guido Cavaletti Abstract Among the different families of intracellular molecules that can be modulated during cell damage and repair, mitogen-activated protein kinases (MAPKs) are particularly interesting because they are involved in several intracellular pathways activated by injury and regeneration signals. Despite most of the studies have been performed in non-neurological models, recently a causal role for MAPKs has been postulated in central nervous system disorders. However, also in some peripheral neuropathies, MAPK changes can occur and these modifications might be relevant in the pathogenesis of the damage as well as during regeneration and repair. In this review, the current knowledge on the role of MAPKs in peripheral neuropathies will be discussed. [source] Sex-dimorphic effects of progesterone and its reduced metabolites on gene expression of myelin proteins by rat Schwann cellsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2006Valerio Magnaghi Abstract Data obtained in our and other laboratories have indicated that progesterone (P) and its derivatives, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), stimulate the expression of two myelin proteins of the peripheral nervous system (PNS) [i.e., glycoprotein zero (P0) and peripheral myelin protein 22 (PMP22)]. We have now considered the effects of P and its derivatives on these and other myelin proteins [i.e., myelin-associated glycoprotein (MAG) and myelin and lymphocyte protein (MAL)] in sex-specific cultures of rat Schwann cells. Gene expression of myelin proteins was assessed by RNase protection assay. Treatment with P or DHP induced a stimulatory effect on P0 mRNA levels in male but not in female Schwann cells. In contrast, treatment with THP increased gene expression of P0 exclusively in female Schwann cells. A similar sex-difference was also evident for other myelin proteins. Indeed, PMP22 expression was stimulated by treatment with P in male cultures, whereas THP induced an increase of mRNA levels in female cultures. Moreover, MAG was stimulated by THP treatment in male cultures only, whereas MAL expression was unaffected by neuroactive steroid treatment in both male and female cultures. In conclusion, the present observations indicate that the effects of neuroactive steroids on myelin proteins are sexually dimorphic. This finding might represent an important background for sex-specific therapies of acquired and inherited peripheral neuropathies. [source] RAT in vivo models of taxanes' peripheral neurotoxicity following chronic intravenous administrationJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004A Canta The "taxanes" family includes some widely used antineoplastic agents, such as paclitaxel and docetaxel. Treatment with these microtubule-stabilizing drugs is often associated with neurotoxicity, a potentially severe side effect limiting the clinical utility of these agents. To study the pathogenesis of taxanes' neurotoxicity and to compare it to the effect of new agents, the availability of reliable in vivo models is warranted. In this study we developed chronic iv models for the assessment of "taxanes" peripheral neurotoxicity. Forty-eight adult Wistar rats were divided into six groups of 8 animals each and treated as follows: paclitaxel or docetaxel at doses of 5, 10, 12.5 mg/kg 1q7d × 4 via a chronic jugular vein implant. The evaluation was based on the assessment of body weight and survival as a measure of general tolerability, and on the measurement of tail nerve conduction velocity, a neurophysiological method previously used in animal models of toxic peripheral neuropathies. The results were compared with those obtained in untreated or vehicle-treated control rats. A clear dose-dependent effect was evident both on general toxicity, and on neurophysiological changes measured at the end of the treatment (untreated controls = 41,9 m/sec, vehicle = 40,3 m/sec; paclitaxel 5 mg/kg = 32,5 m/sec, 10 mg/kg = 28,5 m/sec, 12.5 m/kg = 27,4 m/sec; docetaxel 5 mg/kg = 33,6 m/sec, 10 mg/kg = 27,8 m/sec, 12.5 mg/kg = 27,0 m/sec), demonstrating the usefulness of this new model system to investigate peripheral neurotoxicity mediated by taxanes, and potentially other drugs, under chronic treatment schedules. [source] | |||||||||||||||||||||||||||||||||||||