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Polyneuropathy
Kinds of Polyneuropathy Selected AbstractsPREVALENCE AND RISK FACTORS IN CHRONIC POLYNEUROPATHY IN THE ELDERLYJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002E. Scarpini The elderly are a population at high risk of polyneuropathy because there is a correlation between age and impairment of the peripheral nervous system and because the number of agents that can damage peripheral nerves, including chronic systemic disorders and neurotoxic drugs, increases with age. The Italian Longitudinal Study on Aging (ILSA), a multicenter project designed to study age-associated diseases, collected data from 8 Italian municipalities. For this study, the definition of peripheral neuropathy by P.J. Dyck (1982) was used. However, only peripheral neuropathies with distal and symmetrical involvement of lower limbs were considered. Diagnosis was articulated in two phases: Phase 1 or screening, administered to all participants. The criteria were: a) self reported diagnosis; b) presence of at least one neurological symptom; and c) presence of at least one positive test at short neurological evaluation. A validation of the screening instruments was performed. Phase 2 or clinical confirmation by a neurologist, based on: a) review of the clinical records; b) a neurological examination; c) a clinical history of the disease; and, d) when available, EMG, blood and spinal fluid examination, and a sural nerve biopsy. Three diagnostic categories were identified: possible, probable and definite DSNLL. The neuropathy was classified as definite only when confirmation by a positive EMG was available. A random sample of 5632 subjects aged 65,84 years was evaluated. A total number of 337 DSNLL were identified (possible, probable, defined). The prevalence is 6.5% (95% C.I. 5.8,7.2) in men and women; the rates by age, geographic area, and clinical severity are described, and the prevalence in the different groups of diabetic patients and non-diabetic subjects is analyzed. The prevalence obtained in our study is slightly lower than that in a similar recent multicentric study (IGPSG, 1995), but the diagnostic criteria were different. Diabetes is the most common associated disorder with the 20.8% of association, followed by toxic/drug exposure (5% of association). [source] Polyneuropathy in POEMS syndromeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2008Khaled Ashawesh No abstract is available for this article. [source] Expression Of The Co-Stimulatory Molecule BB-1, The Ligands CTLA-4 and CD28 and Their Mrnas In Chronic Inflammatory Demyelinating PolyneuropathyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001K Murata To examine whether the Schwann cells in patients with autoimmune neuropathies have the potential to behave as professional antigen-presenting cells, we investigated the expression of the co-stimulatory molecules BB-1, B7-1 (CD80), B7-2 (CD86) and their counter-receptors CD28 or CTLA-4 (CD152) at the protein and mRNA levels in sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP), CIDP associated with human immunodeficiency virus infection (HIV-CIDP), IgM paraproteinaemic neuropathy and normal or non-immune axonal neuropathy. In single-and double-labelling experiments, we used the S-100 antigen as a pan-Schwann cell marker, myelin-associated glycoprotein as a marker for myelinating Schwann cells and the fibrillary acidic protein as a marker for unmyelinating Schwann cells. The expression of the B7 family of molecules was limited to BB-1 and was observed only on the Schwann cells. There was constitutive expression of BB-1 on unmyelinating Schwann cells in all nerves studied. However, in CIDP and HIV-CIDP, but not the other diseases, there was prominent upregulation of BB-1 on the myelinating Schwann cells. The endoneurial T cells in the proximity of BB-1-positive Schwann cells expressed the CD28 or CTLA-4 counterreceptors. Reverse transcription-polymerase chain reaction confirmed that these ligands were upregulated only in CIDP. Because the myelinating BB-1-positive Schwann cells expressed HLA-DR antigen, the findings indicate that, in CIDP, Schwann cells possess the necessary markers to function as antigen-presenting cells. [source] Patterns Of Quantitative Sensation Testing Of Hypoesthesia And Hyperalgesia Are Predictive Of Diabetic Polyneuropathy,a Study Of Three CohortsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2000P.J. Dyck OBJECTIVE,To test quantitative sensation testing (QST) patterns of hypoesthesia and hyperalgesia as indicators of diabetic polyneuropathy (DPN) and its severity. RESEARCH DESIGN AND METHODS,We used Computer-Assisted Sensory Examination IV characterized the QST results of the foot of each patient in three diabetic cohorts (similar to 1,500 patients) as hyperesthetic (less than or equal to 2.5th percentile), low-normal (2.5th,50th percentiles), high-normal (50th,97.5th percentiles), or hypoesthetic (greater than or equal to 97.5th percentile), and tested associations with symptoms, impairments, and test abnormalities. RESULTS,Overall neuropathic impairment was most severe in the pancreas-renal transplant and nerve growth factor cohorts, but it was much less severe in the population-based Rochester Diabetic Neuropathy Study (RDNS) cohort. The frequency distribution of sensory abnormalities mirrored this difference. When the QST spectra of diabetic cohorts were compared with those of the control subject cohort for vibration and cooling sensations, the only abnormality observed was hypoesthesia, which was expressed as an increased number of subjects with values at or above the 97.5th percentile or by an increased percentage of cases with high-normal values. Symptoms and impairments of DPN were significantly more frequent in the subjects with Values at or above the 97.5th percentile than in the subjects whose values were between the 50th and 97.5th percentiles. For heat pain (HP) sensation thresholds (intermediate pain severity [HP:5], pain threshold [HP:0.5], and pain-stimulus response slope [HP:5-0.5]), an increased frequency of both hypoalgesia and hyperalgesia was observed (especially in the RDNS cohort). Steeper pain-stimulus response slopes were significantly associated with sensory symptoms, including severity of pain. CONCLUSIONS,1) Decreased vibratory sensation (hypoesthesia) appears to be characteristic of mild DPN, whereas pan-modality hypoesthesia is characteristic of severe DPN. 2) A shift of vibratory and cold detection thresholds and also of attributes of nerve conduction and a measure of autonomic dysfunction from low-normal (2.5th,50th percentiles) to high-normal (50th,37.5th percentiles) appears to precede overt expression of DPN and to thereby provide evidence of subclinical abnormality. 3) Heat stimulus-induced hyperesthesia (low thresholds) occurs especially in mild DPN, and, because it correlates with DPN symptoms and impairments, it must be attributed to hyperalgesia rather than to supersensitivity. Therefore, hypoalgesia or hyperalgesia may be an indicator of early DPN. [source] An Open-Label Study of the Lidocaine Patch 5% in Painful Idiopathic Sensory PolyneuropathyPAIN MEDICINE, Issue 5 2005David N. Herrmann MBBCh ABSTRACT Objective., Painful idiopathic distal sensory polyneuropathy is common, but has been largely ignored as a model for the evaluation of neuropathic pain therapies. We have therefore conducted a safety, tolerability, and effectiveness study of the lidocaine patch 5% in painful idiopathic distal sensory polyneuropathy. Design., A prospective open-label, flexible dosing, 3-week study period with a 5-week extension. Setting., Peripheral Neuropathy clinics and Anesthesiology Clinical Research Center at a tertiary care facility. Patients., Twenty subjects with a diagnosis of idiopathic distal sensory polyneuropathy (with or without associated impaired glucose tolerance), with a baseline mean pain daily rating of ,4 on a visual analog scale. Intervention., Lidocaine patch 5%, maximum of four patches daily for 18 hours. Main Outcome Measure., Change from baseline week to week 3 mean daily diary pain ratings. Secondary endpoints included assessments of safety and tolerability as well as quality of life measures. Results., Subjects with idiopathic distal sensory polyneuropathy, both with and without impaired glucose tolerance, showed significant improvements in pain and quality of life outcome measures over a 3-week treatment period. These improvements were maintained in a subgroup of patients treated for an additional 5 weeks and permitted a taper of concomitant analgesics in 25% of subjects. The lidocaine patch 5% was well tolerated. Conclusions., The lidocaine patch 5% appeared well tolerated and potentially effective in the management of painful idiopathic distal sensory polyneuropathy. Idiopathic distal sensory polyneuropathy is an appropriate patient population for the conduct of clinical trials of neuropathic pain therapies. [source] Whatever the individual says it is: A phenomenological analysis of chronic pain in people with Human Immunodeficiency Virus-associated Distal Symmetrical PolyneuropathyAUSTRALIAN OCCUPATIONAL THERAPY JOURNAL, Issue 4 2005Scott Presnell No abstract is available for this article. [source] Polyneuropathy associated with IgM vs IgG monoclonal gammopathy: comparison between clinical and electrophysiological findingsACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010M. Vrethem Vrethem M, Reiser N, Lauermann C, Svanborg E. Polyneuropathy associated with IgM vs IgG monoclonal gammopathy: comparison between clinical and electrophysiological findings. Acta Neurol Scand: 2010: 122: 52,57. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, The neuropathy associated with IgM monoclonal gammopathy (IgM-MG) is regarded as a sensorimotor, mainly demyelinating neuropathy. It is not fully known whether the neuropathy in IgG-MG is caused by the same mechanisms and shows the same electrophysiological characteristics. We aimed at making a comparison between clinical and neurophysiological findings in these two conditions. Patients and methods,,, Twenty-seven patients with IgM-associated neuropathy [18 with anti-myelin-associated glycoprotein (anti-MAG) antibodies] were compared with 15 age-matched patients with IgG-associated neuropathy. Results,,, Patients with IgM-associated neuropathy (especially those with anti-MAG antibodies) had significantly clinically more severe disabilities with involvement of both motor and sensory functions compared with patients with IgG-associated neuropathy in whom clinical sensory disturbances were more prominent than motor dysfunction. Motor and sensory conduction velocities were significantly lower and distal latencies significantly longer in the IgM group than in the IgG group concerning the median, ulnar and peroneal nerves. Fifty-four per cent of the patients in the IgM group did not present a sensory response of the median nerve vs 13% in the IgG group. There was also a significant difference concerning absent responses from the peroneal and sural nerves in the IgM vs IgG group (peroneal: 48% vs 13%, sural: 88% vs 27%). Conclusion,,, Polyneuropathy associated with IgM-MG, especially when associated with anti-MAG antibodies, appears to have more of a demyelinating involvement that meets the criteria for demyelination. This was not as clear in those associated with IgG. The IgG neuropathy showed less and milder deficit in the electrophysiological studies. [source] EFNS guidelines on pharmacological treatment of neuropathic painEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2006N. Attal Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials. This EFNS Task Force aimed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain. Studies were identified using first the Cochrane Database then Medline. Trials were classified according to the aetiological condition. All class I and II controlled trials (according to EFNS classification of evidence) were assessed, but lower-class studies were considered in conditions that had no top level studies. Only treatments feasible in an outpatient setting were evaluated. Effects on pain symptoms/signs, quality of life and comorbidities were particularly searched for. Most of the randomized controlled trials included patients with postherpetic neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes. These trials provide level A evidence for the efficacy of tricyclic antidepressants, gabapentin, pregabalin and opioids, with a large number of class I trials, followed by topical lidocaine (in PHN) and the newer antidepressants venlafaxine and duloxetine (in PPN). A small number of controlled trials were performed in central pain, trigeminal neuralgia, other peripheral neuropathic pain states and multiple-aetiology neuropathic pains. The main peripheral pain conditions respond similarly well to tricyclic antidepressants, gabapentin, and pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more refractory. There are too few studies on central pain, combination therapy, and head-to-head comparison. For future trials, we recommend to assess quality of life and pain symptoms or signs with standardized tools. [source] Guidelines on routine cerebrospinal fluid analysis.EUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2006Report from an EFNS task force A great variety of neurological diseases require investigation of cerebrospinal fluid (CSF) to prove the diagnosis or to rule out relevant differential diagnoses. The objectives were to evaluate the theoretical background and provide guidelines for clinical use in routine CSF analysis including total protein, albumin, immunoglobulins, glucose, lactate, cell count, cytological staining, and investigation of infectious CSF. The methods included a Systematic Medline search for the above-mentioned variables and review of appropriate publications by one or more of the task force members. Grading of evidence and recommendations was based on consensus by all task force members. It is recommended that CSF should be analysed immediately after collection. If storage is needed 12 ml of CSF should be partitioned into three to four sterile tubes. Albumin CSF/serum ratio (Qalb) should be preferred to total protein measurement and normal upper limits should be related to patients' age. Elevated Qalb is a non-specific finding but occurs mainly in bacterial, cryptococcal, and tuberculous meningitis, leptomingeal metastases as well as acute and chronic demyelinating polyneuropathies. Pathological decrease of the CSF/serum glucose ratio or increased lactate concentration indicates bacterial or fungal meningitis or leptomeningeal metastases. Intrathecal immunoglobulin G synthesis is best demonstrated by isoelectric focusing followed by specific staining. Cellular morphology (cytological staining) should be evaluated whenever pleocytosis is found or leptomeningeal metastases or pathological bleeding is suspected. Computed tomography-negative intrathecal bleeding should be investigated by bilirubin detection. [source] Magnetically evoked motor potentials in demyelinating and axonal polyneuropathy: a comparative studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2000H. Takada We investigated the value of magnetically evoked motor potentials (MEPs) for the differentiation of demyelinating and axonal polyneuropathies. The study population comprised 107 patients, with polyneuropathy verified by electromyography (EMG) and nerve conduction study (NCS), who had also been examined by means of MEP. MEPs were evoked by magnetic stimulation of the cortex and the spinal roots and were recorded from three upper limb muscles and two lower limb muscles bilaterally. From the EMG/NCS results 53 patients were characterized as having primary demyelination (demyelinating patients) and 54 as having axonal involvement (axonal patients). Demyelinating patients were classified as acute (acute inflammatory demyelinating polyradiculoneuropathy: AIDP ) or chronic (chronic inflammatory demyelinating polyradiculoneuropathy: CIDP ) according to the duration of illness. A series of indices were calculated from MEP results. One demyelinating patient and two axonal patients had normal MEPs. The MEPs of the demyelinating patients showed significantly longer peripheral conduction times, larger interside differences and lower amplitudes than the axonal patients. The central conduction index and the amplitudes upon cortical stimulation were significantly higher in patients with CIDP than in those with AIDP. Peripheral conduction time prolonged by more than 85% in at least one of the 10 muscles studied or a peripheral conduction index of above 9.4 were pathognomonic for demyelination . By combining all criteria 75% of the patients could be categorized as CIDP vs. AIDP in accordance with the EMG/NCS diagnosis. Likewise, 83% were categorized correctly as demyelinating versus axonal according to the EMG/NCS data. [source] Prospective investigation of a subcutaneous, implantable central venous access device for therapeutic plasma exchange in adults with neurological disordersJOURNAL OF CLINICAL APHERESIS, Issue 1 2002Basilio Pertiné Abstract Standard alternatives to antecubital access for long-term therapeutic plasma exchange, including percutaneous polyurethane or tunneled silicone catheters, are associated with complications and inconvenience for the patient. We have investigated the Bard CathLink® 20, a subcutaneously implantable central venous access device, as an alternative for outpatient plasma exchange. The CathLink® 20 consists of a funnel-shaped titanium port connected to a soft polyurethane-derived catheter and is accessed percutaneously using an 18-gauge catheter-over-needle Angiocath®. Six patients with paraproteinemic polyneuropathies underwent 64 outpatient plasma exchanges using the CathLink® 20 for access, 31 using 2 CathLink® 20's (draw and return), 20 using a single CathLink® 20 as the draw site and 13 using a single CathLink® 20 as the return site. Mean (± SD) plasma removed was 3,680 ± 551 ml in 115.2 ± 25.3 min. Apheresis personnel were able to access the ports in 1.23 ± 0.6 attempts per port per procedure. Six of 70 planned procedures were aborted: 3 because of failure of an antecubital access site and 3 because of catheter occlusion resolved using a thrombolytic agent. Whole blood flow rate was approximately 54 ml/min, and plasma flow rate was about 32 ml/min for 135 min. Access pressures were stable at ,150 to ,200 torr (P = 0.1395). Return line pressures varied between 90 and 130 torr (P = 0.0147). No patient required hospitalization during the study. Though not optimized for apheresis, the CathLink® 20 provides a reasonable option for chronic apheresis patients who lack adequate peripheral venous access. J. Clin. Apheresis 17:1,6, 2002. © 2002 Wiley-Liss, 2002. [source] Crow,Fukase (POEMS) syndrome: a study of peripheral nerve biopsy in five new casesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2003Claude Vital Abstract, The pathogenesis of Crow,Fukase (POEMS) syndrome is not well known, and in some cases, a definite diagnosis is difficult to establish. Nerve fibers have been studied in about 120 peripheral nerve biopsies (PNBs), and a mixture of axonal and demyelinating lesions were found in most of them. We report five new cases of Crow,Fukase (POEMS) syndrome with ultrastructural examination of their PNBs. In every case, there were features of axonal degeneration and primary demyelination. Interestingly, uncompacted myelin lamellae (UMLs) were present in every case at a percentage of 1,7. The association of UML and Crow,Fukase (POEMS) syndrome was described 20 years ago but was only reported in a few studies and found in 31 of 41 cases. In fact, this association is very significant because apart from Crow,Fukase (POEMS) syndrome, UMLs can only be found with such a frequency in rare cases of Charcot,Marie,Tooth disease type 1B. UML was also reported in acute and chronic inflammatory demyelinating polyneuropathies but at a much lower percentage. Moreover, in our five cases, UML was frequently associated with a decrease in the number of intra-axonal filaments, and this finding raises the problem of relationships between myelin formation and neurofilaments. So far, glomeruloid hemangiomas present in the dermis of some patients are considered as the only specific criteria of Crow,Fukase (POEMS) syndrome, but we think UML can also be regarded as highly suggestive of this entity on condition that a thorough ultrastructural examination of a PNB is performed. [source] PAINFUL NEUROPATHY, MONOCLONAL GAMMOPATHY AND AMYLOID DEPOSITS: RESPONSE TO THERAPY IN 3 CASESJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002Article first published online: 11 MAR 200 Siciliano G.1, D'Avino C.1, Panichi V.2, Azzarà A.3, Del Corona A.1, Pollina L.3, Murri L.1 1Department of Neuroscience, 2Department of Internal Medicine and 3Department of Oncology,University of Pisa-Italy Amyloidosis is a systemic disease with a wide organic involvement. Amyloidotic polyneuropathies may be genetic in their origin or present in association with a number of chronic inflammatory dysimmune disorders. We report on three patients affected by predominantly sensitive polyneuropathy, monoclonal gammopathy and amyloidosis. Patient 1. Woman, 72 years old, with a one year history of painful paraesthesias, ataxic gait and demyelinating predominantly sensitive polyneuropathy at 4 limbs also with involvement of sympathetic fibres. Blood protein electrophoresis showed a monoclonal gammopahty (IgG-k) with normal bone marrow biopsy and positivity for amyloid at fat biopsy. The patient has been treated with melphalan 0.2 mg/Kg/day+prednisone 100 mg/day for 7 days each month for 6 months with good efficacy and only a transient reduction in platelet and white blood cells count. Patient 2. Man, 60 years old, new diagnosis of diabetes with a 9 month history of painful paraesthesias and hyposthenia, a demyelinating sensory-motor polyneuropathy at 4 limbs. The patient presented an IgG-, monoclonal gammopathy with normal bone marrow biopsy, fat biopsy but not sural nerve biopsy positive for amyloid. The patient underwent melphalan+prednisone therapy, with insulinic control of glycemia. He presented a clear-cut improvement in sensitive-motor symptomatology. Patient 3. Man, 72 years old, with a 15 year history of ulcerous rectocolites. Since 1998 started complaining of paraesthesias and disaesthesias at four limbs associated with gait disturbances. The patient presented an IgG-, monoclonal gammopathy with normal bone marrow aspiration and elevated serum Interleukin-6 levels, fat biopsy positive for amyloid, and high anti-MAG antibodies titer (1:100000). Because of RCU, melphalan therapy was excluded and the patient is at the moment under fludarabine (25 mg/m2/day) ev for 5 days each 6 weeks for 6 bouts. [source] Isolation and characterization of bacteriophages specific for Campylobacter jejuniMICROBIOLOGY AND IMMUNOLOGY, Issue 10 2009Sunyoung Hwang ABSTRACT Human infection by Campylobacter jejuni is mainly through the consumption of contaminated poultry products, which results in gastroenteritis and, rarely, bacteremia and polyneuropathies. In this study, six C. jejuni -specific bacteriophages (CPS1,6) were isolated by the spot-on-the-lawn technique from chicken samples in Korea and characterized for potential use as biocontrol agents. All isolated bacteriophages exhibited a high specificity, being able to lyse only C. jejuni, but not other Gram,negative bacteria, including C. coli, Escherichia coli, Salmonella spp., and Gram,positive bacteria. Bacteriophages contain an icosahedral head and a contractile tail sheath in transmission electron microscopy, and possess ds-DNA with an average genome size of approximately 145 kb; therefore, all bacteriophages are categorized into the Myoviridae family. Bacterial lysis studies in liquid media revealed that CPS2 could be used to control the growth of C. jejuni. [source] Current treatments of chronic immune-mediated demyelinating polyneuropathiesMUSCLE AND NERVE, Issue 5 2009Thomas H. Brannagan III MD Abstract Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and anti,myelin-associated glycoprotein (anti-MAG) neuropathy are three demyelinating acquired neuropathies, with distinct responses to immunotherapy. In placebo-controlled, double-blind, randomized trials, intravenous immunoglobulin (IVIg) has been effective for CIDP and MMN, and plasmapheresis has been effective for CIDP. Corticosteroids have been beneficial in controlled trials for CIDP. Other agents, including cyclophosphamide, rituximab, azathioprine, cyclosporine, interferons, fludarabine, mycophenolate mofetil, and etanercept, have been reported to benefit some patients with inflammatory demyelinating neuropathies in case series and case reports. This review examines the use and toxicity associated with these immunotherapy medications in treating patients with chronic immune-mediated demyelinating neuropathies. Muscle Nerve, 2009 [source] Ganglioside mimicry and peripheral nerve diseaseMUSCLE AND NERVE, Issue 6 2007Nobuhiro Yuki MD Abstract Four criteria must be satisfied to conclude that a given microorganism causes Guillain,Barré (GBS) or Fisher (FS) syndrome associated with anti-ganglioside antibodies: (1) an epidemiological association between the infecting microbe and GBS or FS; (2) isolation in the acute progressive phase of illness of that microorganism from GBS or FS patients with associated anti-ganglioside IgG antibodies; (3) identification of a microbial ganglioside mimic; and (4) a GBS or FS with associated anti-ganglioside antibodies model produced by sensitization with the microbe itself or its component, as well as with ganglioside. Campylobacter jejuni is a definitive causative microorganism of acute motor axonal neuropathy and may cause FS and related conditions. Haemophilus influenzae and Mycoplasma pneumoniae are possible causative microorganisms of acute motor axonal neuropathy or FS. Acute and chronic inflammatory demyelinating polyneuropathies may be produced by mechanisms other than ganglioside mimicry. Muscle Nerve, 2007 [source] Comparison between impairment and disability scales in immune-mediated polyneuropathiesMUSCLE AND NERVE, Issue 1 2003Ingemar S.J. Merkies MD Abstract The ability of a scale to detect clinical relevant changes over time, i.e., its "responsiveness," may help clinicians to choose among valid and reliable measures. Therefore, we investigated the responsiveness' rank ordering (best to worse) of six selected valid and reliable scales, namely the Medical Research Council (MRC)-sumscore, sensory-sumscore, grip-strength (Vigorimeter), nine-hole peg, ten-meters walking, and a disability-sumscore, in immune-mediated polyneuropathies. Patients with newly diagnosed Guillain,Barré syndrome (n = 7) or chronic inflammatory demyelinating polyneuropathy (n = 13) were examined over 52 weeks. Responsiveness of each scale was measured using different methods (effect-size, standardized response mean score, Wilcoxon matched-pairs signed-rank, and a newly devised Schmitz's distribution-free responsiveness score), and the obtained scores in each method were plotted against the follow-up period, thus allowing area-under-the-curve calculations (higher area-under-the-curve indicating better responsiveness). Also, longitudinal correlations were performed between the scales' values and patients' own clinical judgments (deteriorated, unchanged, improved) (higher correlation = better responsiveness). A consistent rank ordering was observed in each technique with the disability-sumscore, MRC-sumscore, and Vigorimeter being among the best responsive scales. Hence, the primary use of these measures is suggested in studies of immune-mediated polyneuropathies. Muscle Nerve 28: 93,100, 2003 [source] Is reflex sympathetic dystrophy/complex regional pain syndrome type I a small-fiber neuropathy?,ANNALS OF NEUROLOGY, Issue 6 2009Anne Louise Oaklander MD Neurologist S. Weir Mitchell first described "causalgia" following wartime nerve injury, with its persistent distal limb burning pain, swelling, and abnormal skin color, temperature, and sweating. Similar post-traumatic symptoms were later identified in patients without overt nerve injuries after trauma. This was labeled reflex sympathetic dystrophy (RSD; now complex regional pain syndrome type I [CRPS-I]). The pathophysiology of symptoms is unknown and treatment options are limited. We propose that persistent RSD/CRPS-I is a post-traumatic neuralgia associated with distal degeneration of small-diameter peripheral axons. Small-fiber lesions are easily missed on examination and are undetected by standard electrophysiological testing. Most CRPS features,spreading pain and skin hypersensitivity, vasomotor instability, osteopenia, edema, and abnormal sweating,are explicable by small-fiber dysfunction. Small fibers sense pain and temperature but also regulate tissue function through neuroeffector actions. Indeed, small-fiber,predominant polyneuropathies cause CRPS-like abnormalities, and pathological studies of nerves from chronic CRPS-I patients confirm small-fiber,predominant pathology. Small distal nerve injuries in rodents reproduce many CRPS features, further supporting this hypothesis. CRPS symptoms likely reflect combined effects of axonal degeneration and plasticity, inappropriate firing and neurosecretion by residual axons, and denervation supersensitivity. The resulting tissue edema, hypoxia, and secondary central nervous system changes can exacerbate symptoms and perpetuate pathology. Restoring the interest of neurologists in RSD/CRPS should improve patient care and broaden our knowledge of small-fiber functions. Ann Neurol 2009;65:629,638 [source] FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous systemBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2009Volker Brinkmann FTY720 (fingolimod) is a first-in-class sphingosine 1-phosphate (S1P) receptor modulator that was highly effective in Phase II clinical trials for Multiple Sclerosis (MS). FTY720 is phosphorylated in vivo by sphingosine kinase-2 to form the active moiety FTY720-phosphate that binds to four of the five G protein-coupled S1P receptor subtypes. Studies using conditional S1P1 receptor-deficient and sphingosine kinase-deficient mice showed that the egress of lymphocytes from lymph nodes requires signalling of lymphocytic S1P1 receptors by the endogenous ligand S1P. The S1P mimetic FTY720-phosphate causes internalization and degradation of cell membrane-expressed S1P1, thereby antagonizing S1P action at the receptor. In models of human MS and demyelinating polyneuropathies, functional antagonism of lymphocytic S1P1 slows S1P-driven egress of lymphocytes from lymph nodes, thereby reducing the numbers of autoaggressive TH17 cells that recirculate via lymph and blood to the central nervous system and the sciatic/ischiatic nerves. Based on its lipophilic nature, FTY720 crosses the blood,brain barrier, and ongoing experiments suggest that the drug also down-modulates S1P1 in neural cells/astrocytes to reduce astrogliosis, a phenomenon associated with neurodegeneration in MS. This may help restore gap-junctional communication of astrocytes with neurons and cells of the blood,brain barrier. Additional effects may result from (down-) modulation of S1P3 in astrocytes and of S1P1 and S1P5 in oligodendrocytes. In conclusion, FTY720 may act through immune-based and central mechanisms to reduce inflammation and support structural restoration of the central nervous system parenchyma. Beyond the autoimmune indications, very recent studies suggest that short-term, low-dose administration of FTY720 could help treat chronic (viral) infections. Differential effects of the drug on the trafficking of naïve, central memory and effector memory T cell subsets are discussed. [source] Clinical and electromyographic deep tendon reflexes in polyneuropathy: diagnostic value and prevalence,ACTA NEUROLOGICA SCANDINAVICA, Issue 4 2009K. R. Sharma Background,,, Evidence is accumulating that patients with polyneuropathy may present with normal clinical deep tendon reflexes (C-DTR). There are few studies that assessed the diagnostic utility of electromyographically recorded DTR (Er-DTR) in patients with polyneuropathy. Objectives,,, The objectives of this study were twofold: (i) to evaluate the prevalence of preserved C-DTR in polyneuropathy; (ii) diagnostic value of Er-DTR latency measurement in patients with polyneuropathy. Methods,,, We prospectively studied 38 controls and 185 patients with polyneuropathy. All subjects had evaluation of C-DTR, Er-DTR obtained from right biceps brachii (BR), right patellar (PR) and bilateral ankle reflexes (AR). Results,,, Of these 185 patients, 118 (63.8%) had chronic axonal neuropathy (CAN), 49 (26.5%) demyelinating polyradiculoneuropathy (DPN) and 18 (9.7%) small fiber neuropathy (SFN). The C-DTR were normal in 65 patients whereas 39 of these 65 (60%) patients had abnormalities of Er-DTR at one or more sites. Er-DTR latencies in patients with polyneuropathies were prolonged at all sites compared with controls (P < 0.01). Among patients with various types of polyneuropathies the Er-DTR, mean latencies at all the sites and latency indicative of demyelination (>150% of the normal mean) were higher in patients with DPN than that of CAN or SFN (P < 0.01). Conclusions,,, We conclude that C-DTR are preserved in 35.1% of the patients with polyneuropathies and Er-DTR should be performed in such patients in order to provide electrophysiological evidence of a polyneuropathy. Er-DTR are useful in distinguishing axonal from demyelinating disorders of peripheral nerve, and detection of subclinical involvement of large fibers in SFN. [source] Pitfalls in the Diagnosis of Cerebellar InfarctionACADEMIC EMERGENCY MEDICINE, Issue 1 2007Sean I. Savitz MD Abstract Background Cerebellar infarctions are an important cause of neurologic disease. Failure to recognize and rapidly diagnose cerebellar infarction may lead to serious morbidity and mortality due to hydrocephalus and brain stem infarction. Objectives To identify sources of preventable medical errors, the authors obtained pilot data on cerebellar ischemic strokes that were initially misdiagnosed in the emergency department. Methods Fifteen cases of misdiagnosed cerebellar infarctions were collected, all seen, or reviewed by the authors during a five-year period. For each patient, they report the presenting symptoms, the findings on neurologic examination performed in the emergency department, specific areas of the examination not performed or documented, diagnostic testing, the follow-up course after misdiagnosis, and outcome. The different types of errors leading to misdiagnosis are categorized. Results Half of the patients were younger than 50 years and presented with headache and dizziness. All patients had either incomplete or poorly documented neurologic examinations. Almost all patients had a computed tomographic scan of the head interpreted as normal, and most of these patients underwent subsequent magnetic resonance imaging showing cerebellar infarction. The initial incorrect diagnoses included migraine, toxic encephalopathy, gastritis, meningitis, myocardial infarction, and polyneuropathy. The overall mortality in this patient cohort was 40%. Among the survivors, about 50% had disabling deficits. Pitfalls leading to misdiagnosis involved the clinical evaluation, diagnostic testing, and establishing a diagnosis and disposition. Conclusions This study demonstrates how the diagnosis of cerebellar infarction can be missed or delayed in patients presenting to the emergency department. [source] Treatment of symptomatic diabetic neuropathyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2003Andrew J. M. Boulton Abstract Painful diabetic neuropathy is a common and particularly unpleasant long-term complication of diabetes that affects a significant minority of patients with distal polyneuropathy. After exclusion of other causes of neuropathic pain, attention should be focused on achieving optimal and stable glycaemic control avoiding flux of blood glucose levels, which have been shown to aggravate pain. Most patients will require pain control therapy and whilst the tricyclic drugs remain a first-line approach, their use is often hampered by predictable but troublesome side effects. Gabapentin, the only agent specifically licensed for the treatment of neuropathic pain in the United Kingdom, is useful in diabetic neuropathy and is generally better tolerated than the tricyclics. Additionally, other pharmacological and non-pharmacological pain management approaches may be useful. Patient education has a significant role to play in the avoidance of late neurological complications. Copyright © 2003 John Wiley & Sons, Ltd. [source] Foot temperature in diabetic polyneuropathy: innocent bystander or unrecognized accomplice?DIABETIC MEDICINE, Issue 3 2005S. B. Rutkove Abstract Aim To explore mechanisms by which temperature could influence the pathogenesis and symptoms of diabetic polyneuropathy. Methods We conducted a literature review attempting to identify mechanisms by which diabetic polyneuropathy could be affected by temperature. Results Cooling can theoretically hasten the progression of diabetic polyneuropathy through several different mechanisms. Specifically, cooling can enhance neuronal ischaemia, increase formation of reactive oxygen species, slow axonal transport, increase protein kinase C activity, and interfere with immune function. Short-term temperature fluctuations (both warming and cooling) can initiate and exacerbate neuropathic pain by causing neuronal hyperexcitability and functional deafferentation. Although normal fluctuations of distal extremity temperature may be sufficient for these effects, impaired thermoregulation may make the distal extremities more susceptible to temperature extremes. Eventually, a ,vicious cycle' may ensue, resulting in neuronal deterioration with further disruption of temperature regulation. Limited epidemiological data suggest a higher prevalence of diabetic polyneuropathy in populations living in colder locations, supporting our hypothesis. Conclusions Variations in foot temperature may play an important but as yet unrecognized role in the development and symptoms of diabetic polyneuropathy. Further basic and clinical research exploring this concept could help elucidate the natural history of diabetic polyneuropathy and lead to novel therapeutic strategies. [source] The value of the Rydel-Seiffer tuning fork as a predictor of diabetic polyneuropathy compared with a neurothesiometerDIABETIC MEDICINE, Issue 6 2004T. Kästenbauer Abstract Aims The aim of the study was to investigate the predictive value of the Rydel-Seiffer tuning fork for detecting diabetic neuropathy and to compare it with an electronic neurothesiometer. Methods In 2022 consecutive diabetic subjects, peripheral polyneuropathy was diagnosed by vibration perception threshold (VPT) at the tip of both great toes using a 128-Hz tuning fork and a neurothesiometer, by simple bedside tests and by the presence of neuropathic symptoms. These evaluations were further combined to diagnose peripheral nerve dysfunction (abnormal bedside tests) and symptomatic neuropathy. VPT was also measured in 175 non-diabetic control subjects to define normal values. Results VPT was normal in 1917 subjects and abnormal in 105 (5.2%) patients when measured by the tuning fork. Patients with an abnormal vibration test were significantly (P < 0.0001) older than subjects with a normal vibration sense, while diabetes duration and HbA1c of the former were also significantly elevated. The same was true for the percentages of an abnormal 10-g monofilament test (66.7% vs. 7.2%, P < 0.0001) and a missing Achilles' tendon reflex (68.6% vs. 24.8%, P < 0.0001). Finally, the VPT measured by the neurothesiometer was 2.5 times higher in patients with an abnormal tuning fork test (32.0 ± 9.8 vs. 12.5 ± 6.4 V, P < 0.0001). The plot of the difference of both methods against their mean yielded a good agreement of the two VPT measurements, and the tuning fork had a high sensitivity and positive predictive value for the diagnosis of abnormal bedside tests and for symptomatic neuropathy. Conclusion The tuning fork reliably detected peripheral neuropathy in comparison with the neurothesiometer. A tuning fork is a useful screening test for diabetic neuropathy. [source] Treatment of symptomatic diabetic polyneuropathy with the antioxidant ,-lipoic acid: a meta-analysisDIABETIC MEDICINE, Issue 2 2004D. Ziegler Abstract Aims To determine the efficacy and safety of 600 mg of ,-lipoic acid given intravenously over 3 weeks in diabetic patients with symptomatic polyneuropathy. Methods We searched the database of VIATRIS GmbH, Frankfurt, Germany, for clinical trials of ,-lipoic acid according to the following prerequisites: randomized, double-masked, placebo-controlled, parallel-group trial using ,-lipoic acid infusions of 600 mg i.v. per day for 3 weeks, except for weekends, in diabetic patients with positive sensory symptoms of polyneuropathy which were scored by the Total Symptom Score (TSS) in the feet on a daily basis. Four trials (ALADIN I, ALADIN III, SYDNEY, NATHAN II) comprised n = 1258 patients (,-lipoic acid n = 716; placebo n = 542) met these eligibility criteria and were included in a meta-analysis based on the intention-to-treat principle. Primary analysis involved a comparison of the differences in TSS from baseline to the end of i.v. Treatment between the groups treated with ,-lipoic acid or placebo. Secondary analyses included daily changes in TSS, responder rates (, 50% improvement in TSS), individual TSS components, Neuropathy Impairment Score (NIS), NIS of the lower limbs (NIS-LL), individual NIS-LL components, and the rates of adverse events. Results After 3 weeks the relative difference in favour of ,-lipoic acid vs. placebo was 24.1% (13.5, 33.4) (geometric mean with 95% confidence interval) for TSS and 16.0% (5.7, 25.2) for NIS-LL. The responder rates were 52.7% in patients treated with ,-lipoic acid and 36.9% in those on placebo (P < 0.05). On a daily basis there was a continuous increase in the magnitude of TSS improvement in favour of ,-lipoic acid vs. placebo which was noted first after 8 days of treatment. Among the individual components of the TSS, pain, burning, and numbness decreased in favour of ,-lipoic acid compared with placebo, while among the NIS-LL components pin-prick and touch-pressure sensation as well as ankle reflexes were improved in favour of ,-lipoic acid after 3 weeks. The rates of adverse events did not differ between the groups. Conclusions The results of this meta-analysis provide evidence that treatment with ,-lipoic acid (600 mg/day i.v.) over 3 weeks is safe and significantly improves both positive neuropathic symptoms and neuropathic deficits to a clinically meaningful degree in diabetic patients with symptomatic polyneuropathy. Diabet. Med. 21, 114,121 (2004) [source] ,Numbness of the feet' is a poor indicator for polyneuropathy in Type 2 diabetic patientsDIABETIC MEDICINE, Issue 2 2000L. V. Franse Summary Aims To identify neuropathic sensory symptoms associated with a clinical neurological examination (CNE) and to investigate whether these symptoms could be used as a diagnostic or screening tool for diabetic polyneuropathy in general practice. Methods Five hundred and eighty-eight patients with Type 2 diabetes, recruited from 26 general practices in the Netherlands, underwent a CNE and completed a diabetes symptom checklist that included 10 items on neuropathic sensory symptoms. Linear regression analyses were performed to assess the association between neuropathic symptoms and CNE. Receiver operating characteristic (ROC) curves were created to assess the diagnostic properties of neuropathic symptoms. Results In this population, with a mean age of 66.8 years, 32% were identified with diabetic polyneuropathy according to the CNE. Variables that showed the strongest association with CNE score were age (, = 0.41), symptoms of sensory alteration (, = 0.27), and the item ,numbness of the feet' (, = 0.35) in particular. ROC curves showed that prediction of diabetic polyneuropathy from these symptoms was unsatisfying. The sensitivity and specificity of daily symptoms of ,numbness of the feet' were 28% and 93%, respectively, in patients <,68 years, and 22% and 92%, respectively, in patients ,,68 years. Conclusions Identification of neuropathic sensory symptoms is not useful as a diagnostic or even a screening tool in the assessment of diabetic neuropathy in daily practice. Therefore, the results reported in this paper mandate an annual foot examination by the general practitioner. [source] Polyacrylamide gel electrophoresis followed by sodium dodecyl sulfate gradient polyacrylamide gel electrophoresis for the study of the dimer to monomer transition of human transthyretinELECTROPHORESIS, Issue 14 2003Klaus Altland Abstract Familial amyloidotic polyneuropathy (FAP) is caused by mutations which destabilize transthyretin (TTR) and facilitate the aggregation into extracellular amyloid fibrils preferentially in peripheral nerve and heart tissues. Therapeutic and preventive trials for FAP at the plasma TTR level require a careful study of the destabilization of TTR under variable conditions. We have developed a simple double one-dimensional (D1-D) electrophoretic procedure with polyacrylamide gel electrophoresis (PAGE) followed by sodium dodecylsulfate (SDS) gradient PAGE to study the dimer to monomer transition. TTR is first isolated by PAGE from other plasma proteins. The gel strip containing the TTR fraction is incubated in 2% SDS under varying conditions of temperature, buffer composition, pH, and additives like urea and/or a sulfhydryl-reactive agent, followed by SDS-gradient PAGE for the separation of TTR dimers and monomers. We demonstrate that an unidirectional dimer to monomer transition of normal TTR is achieved at 70,80°C in neutral to mild alkaline buffers or at 37°C and slightly acidic pH (6,7). Addition of urea favors the transition into monomers. Amyloidogenic mutations like amyloidogenic TTR (ATTR)-V30M or ATTR-I107V favor the transition into monomers in buffer systems close to the physiological pH of human plasma. We conclude that this finding has to be considered by any hypothesis on ATTR-derived amyloidogenesis. [source] Electrophysiological sensory demyelination in typical chronic inflammatory demyelinating polyneuropathyEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2010Y. A. Rajabally Background:, The presence of electrophysiological demyelination of sensory nerves is not routinely assessed in the evaluation of suspected chronic inflammatory demyelinating polyneuropathy (CIDP). Whether this can be useful is unknown. Methods:, We compared, using surface recording techniques, in 19 patients with typical CIDP and 26 controls with distal large fibre sensory axonal neuropathy, the forearm median sensory conductions, sensory nerve action potential (SNAP) amplitudes and durations and sensory nerve conduction velocities (SNCVs) of median, radial and sural nerves. Results:, Median nerve sensory conduction block (SCB) across the forearm was greater in CIDP patients than in controls (P = 0.005). SNAP durations were longer in CIDP patients for median (P = 0.001) and sural nerves (P = 0.004). Receiver operating characteristic (ROC) curves provided sensitive (>40%) and specific (>95%) cut-offs for median nerve SCB as well as median and sural SNAP durations. SNCVs were significantly slower for median and sural nerves in CIDP patients, but ROC curves did not demonstrate cut-offs with useful sensitivities/specificities. Median SCB or prolonged median SNAP duration or prolonged sural SNAP duration offered a sensitivity of 73.7% for CIDP and specificity of 96.2%. Used as additional parameters, they improved diagnostic sensitivity of the American Academy of Neurology (AAN) criteria for CIDP of 1991, from 42.1% to 78.9% in this population, with preserved specificity of 100%. Discussion:, Sensory electrophysiological demyelination is present and may be diagnostically useful in typical CIDP. SCB detection and SNAP duration prolongation appear to represent more useful markers of demyelination than SNCV reduction. [source] Immune therapy for chronic inflammatory demyelinating polyneuropathy: from clinical trials to real-lifeEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2010Y. A. Rajabally No abstract is available for this article. [source] Penetrance estimation of TTR familial amyloid polyneuropathy (type I) in Brazilian familiesEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2009M. A. C. Saporta Background and purpose:, Familial amyloid polyneuropathy (FAP) type I is a severe autosomal dominant inherited neuropathy associated with mutations in the transthyretin (TTR) gene. Significant phenotypic variability is seen amongst families with distinct geographic origin, especially regarding penetrance and age of onset. The aim of this study was to estimate the penetrance of FAP in Brazilian families. Methods:, Twenty-two distinct families were ascertained through genetically confirmed index cases and included in this study. Genealogical and clinical data were obtained from a total of 623 individuals, including 126 affected by FAP. In 15 families, TTR genotyping was performed in all available relatives (n = 86), after informed written consent. Seven families did not consent for genetic testing, but agreed to provide clinical and genealogical data. Penetrance was estimated using a previously described method based on survival analysis and corrected for ascertainment bias. Results:, Mean age of onset in our sample was 34.5 years, with a significant earlier onset in males (31.1 vs. 35.9, P < 0.0001). The penetrance of FAP in our sample was estimated as 83% (95% CI: 66,99) after 60 years. Conclusion:, Our results provide new information on FAP in Brazilian patients and may be helpful in the genetic counseling of this population. [source] | |||||||||||||||||||||||||||||||