Electrophysiological Evidence Of Neuropathy Research Articles

Sensory Neuronopathies: Clinical Presentation, Management, and Outcome.

Sensory neuronopathies (SNNs) are a rare group of pure sensory disorders causing asymmetrical, multifocal pattern of sensory loss with distinct clinical and electrophysiological features. We aimed to study the clinical features and etiology and share the experience of treating SNN from our center. A prospective observational study was conducted over 3 years. Patients with predominant sensory complaints and electrophysiological evidence of neuropathy were evaluated. Possible/probable SNN was diagnosed using Camdessanch´e criteria. Detailed workup was done to determine the etiology and treatment given accordingly. Follow-up was done and response to treatment was assessed using modified Rankin Scale grading at 12 months. Fourteen patients with SNN were studied. Two (14.3%) patients were diagnosed with Sjogren's syndrome (SS-SNN), two (14.3%) with paraneoplastic syndrome, one (7.1%) with leprous ganglionitis, and nine (64.3%) were idiopathic sensory neuronopathy (I-SNN) cases. Improvement occurred in nine (64.3%), stability in three (21.4%), and worsening in two (14.3%) patients. Out of 11 SS-SNN and I-SNN patients, eight showed improvement on follow-up, seven with injection rituximab (RTX) and one with azathioprine. We found positive correlation between RTX treatment and improvement on follow-up (P = 0.0256). Six (66.66%) out of nine I-SNN patients had early initiation of immunotherapy, of which all improved. There was positive correlation between early treatment initiation time in I-SNN patients and improvement (P = 0.0119). Promising results were noted in SS-SNN and I-SNN patients with intensive treatment approach using RTX. Hit hard and early treatment approach is crucial for achieving improvement in sensory neuronopathies.

Vincristine-induced peripheral neuropathy in survivors of childhood acute lymphoblastic leukaemia.

Vincristine, an essential component of childhood acute lymphoblastic leukaemia (ALL) therapeutic protocols, is associated with dose-dependent neurotoxicity, but its long-term morbidity in treated children has not been clearly elucidated. The aim of this study is to determine the prevalence of vincristine-induced peripheral neuropathy (VIPN) among Malaysian childhood ALL survivors and its impact on motor function and quality of life. Survivors of childhood ALL aged 4-18 years who had completed chemotherapy for 2 years or more were evaluated for VIPN using both the clinical Total Neuropathy Score (cTNS) and nerve conduction studies. Motor function and quality of life of the survivors were assessed via the Bruininks-Oseretsky Test of Motor Proficiency Brief Form, Second Edition (BOT-2 Brief Form) and the Paediatric Quality of Life version 4.0 Generic Core Scales (PedsQL4.0) questionnaire, respectively. One hundred and one survivors with a duration of follow-up ranging from 2.0 to 10.3 years were recruited. Twenty-seven (26.7%) had abnormal cTNS scores and 69 (68.3%) had electrophysiological evidence of neuropathy. Of these, 16 (15.8%) had combined clinical and electrophysiological neuropathy (VIPN). Those previously treated on the intermediate- or high-risk treatment stratification arms had a higher risk of developing VIPN (67.3 vs. 32.7%; odds ratio [OR]: 9.06, 95% confidence interval [CI]: 1.14-71.86; P = 0.014). Survivors with VIPN had significantly lower quality of life scores in the physical (P = 0.024) and social domains (P = 0.039) compared with peers without VIPN, but no association with poorer motor function was observed. Sixteen percent of ALL survivors had VIPN. VIPN should be increasingly recognised as a late effect of chemotherapy, as it significantly affects physical and social function quality of life.

Symptomatic and Electrodiagnostic Features of Peripheral Neuropathy in Scleroderma

To determine the prevalence of peripheral neuropathy in scleroderma. The prevalence of length-dependent peripheral neuropathy was rigorously assessed using signs and symptoms of neuropathy derived from the Total Neuropathy Score (TNS), and standardized nerve conduction study (NCS). All subjects underwent TNS and NCS. Those who were symptomatic or had NCS evidence of peripheral neuropathy underwent laboratory evaluation for secondary causes of neuropathy. A total of 130 subjects were approached for participation and 60 enrolled. Of the 60 subjects, 50 (83.3%) were female and 37 (61.7%) were of the limited cutaneous subtype. The mean ± SD age was 55 ± 11.1 years, and mean ± SD disease duration was 15.3 ± 10.1 years. A total of 17 of 60 (28%) had evidence of a peripheral neuropathy as defined by the presence of neuropathic symptoms on the TNS (12 of 60) and/or electrophysiologic evidence of neuropathy (5 subjects with neuropathic symptoms and 5 without neuropathic symptoms). Subjects with neuropathy were more likely to be male (60% versus 40%; P = 0.02), African American (41% versus 4.6%; P = 0.001), have diabetes mellitus (17.7% versus 0%; P = 0.02), have limited cutaneous scleroderma (82.3% versus 53.5%; P = 0.04), and have anti-U1 RNP antibodies (23.5% versus 0%; P = 0.009) than those without neuropathy. A potential nonscleroderma etiology for the peripheral neuropathy such as diabetes mellitus was found in 82.3% (14 of 17) of subjects with neuropathy. While symptoms or objective evidence of peripheral neuropathy are common among patients with scleroderma, the cause may often be attributed to comorbid nonscleroderma-related conditions.

Divergent Effects of T Cell Costimulation and Inflammatory Cytokine Production on Autoimmune Peripheral Neuropathy Provoked by Aire Deficiency

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

Electrophysiological evaluation of spinocerebellar ataxias 1, 2 and 3

Introduction Subclinical neuropathy is an important feature of spinocerebellar ataxias (SCA) but the true prevalence and electrophysiological characteristics in genetically proven patients of SCA 1, 2 and 3 are largely unknown. Methods We prospectively compared the electrophysiological characteristics of neuropathy in 61 genetically confirmed cases of SCA (SCA1 = 28, SCA2 = 16 and SCA3 = 17). Nerve conduction studies were performed in at least one sensory and one motor nerve, in right upper and lower limb using standard methods. Results The mean age of patients and duration of illness were comparable among SCA groups (mean age (years): SCA1—34.1 ± 12.7, SCA2—35.2 ± 13.9 and SCA3—38.1 ± 11.3; mean duration (years): SCA1—5.4, SCA2—6.1, and SCA3—4.4). Electrophysiological evidence of neuropathy was highest in SCA1 (96.4%), followed by SCA3 (94.1% and SCA2 (87.5%). A mixed sensorimotor neuropathy was commonly observed in all the subgroups (SCA1—78.6%, SCA2—50%, and SCA3—41.2%). Pure sensory neuropathy was most common in SCA3 (55.9%), followed by 31.3% in SCA2 and 17.9% in SCA1. Pure motor neuropathy was uncommon (6.3% in SCA2 and none in SCA1 and SCA3). Conclusions Electrophysiological evidence of mixed sensorimotor and pure sensory neuropathy is seen in all the three subtypes of SCAs, while pure motor neuropathy is distinctly uncommon.

Urodynamic Profile of Diabetic Patients With Lower Urinary Tract Symptoms: Association of Diabetic Cystopathy With Autonomic and Peripheral Neuropathy

To evaluate the association between diabetic cystopathy (DC) and neuropathy (autonomic and peripheral) in patients with diabetes mellitus (DM) presenting with lower urinary tract symptoms (LUTS). Men with DM who presented with bothersome LUTS were enrolled from January 2008 to June 2009. Their demographic and clinical profiles were noted. Multichannel urodynamic studies were performed using the Solar Silver digital urodynamic apparatus. Hand and foot sympathetic skin responses, and motor and sensory nerve-conduction velocity studies were performed using the Meditronic electromyographic/evoked potentials system. A total of 52 men (mean age 61.3 ± 12.1 years, DM duration 11.0 ± 7.5 years) completed the study protocol. Of these 52 men, abnormal sympathetic skin responses, motor and sensory nerve-conduction velocity studies, and combined neuropathy (all 3 tests abnormal) were noted in 80.7% 57.7%, 57.7%, and 51.9%, respectively. Urodynamic studies showed impaired first sensation (>250 mL), increased capacity (>600 mL), detrusor underactivity, detrusor overactivity, high postvoid residual urine volume (more than one third of capacity), and bladder outlet obstruction (Abrams-Griffiths number >40) in 23.1%, 25.0%, 78.8%, 38.5%, 65.4%, and 28.8% of the men, respectively. Both sensory and motor DC correlated with abnormal motor and sensory nerve-conduction velocity studies (P = .015 and P = .005, respectively). Only motor DC correlated with abnormal sympathetic skin responses (P = .015). The correlations were stronger in the presence of combined neuropathy (sensory DC, P = .005; motor DC, P = .0001). Men with DM and LUTS can present with varied urodynamic findings, apart from the classic sensory or motor cystopathy. A large proportion of these patients will have electrophysiologic evidence of neuropathy, and electrophysiologic evidence of neuropathy can moderately predict the presence of cystopathy.

A clinical, electrophysiological, and pathological study of neuropathy in rheumatoid arthritis

Neuropathy in rheumatoid arthritis (RA) may result secondary to entrapment, vasculitis, and drug toxicity. We aimed to study clinical and electrophysiological neuropathy and pathological changes in sural nerve in patients with RA. One hundred eight patients of RA, fulfilling American College of Rheumatology 1987 criteria (mean age, 45.83 years; M/F 1:3, 80.3% seropositive) were examined clinically and electrophysiologically for evidence of peripheral neuropathy. Sural nerve biopsies were performed in the involved cases. In all RA patient medications, disease activity, results of blood tests, and X-rays of affected joints were recorded. Twenty-three patients complained of paresthesias in the extremities. Vibration sensations were decreased in 9, and tendon reflexes were decreased or absent in 28 patients. Sixty-two (57.4%) patients had electrophysiologic evidence of neuropathy. Of these 53 (85.5%) patients had pure sensory or sensory motor axonal neuropathy (mononeuritis multiplex, n = 7), while 9 (14.5%) had demyelinating neuropathy (chronic inflammatory demyelinating polyneuropathy, n = 1). Carpal tunnel syndrome was seen in 11 (10.1%) patients (associated with neuropathy in 6). Of 23 sural nerve biopsies available, perineurial thickening (n = 5, amyloid deposits n = 4), perivascular lymphomononuclear cell infiltrate (n = 4), loss of myelin fibers (n = 2), and necrotizing vasculitis (n = 1) were found. Clinically, however, seven patients had evidence of cutaneous vasculitis. Comparing the clinical characteristics of the patients with or without electrophysiological neuropathy, absence of deep tendon jerks (p < 0.005) and presence of extra articular manifestations (p < 0.01) were conspicuous in the neuropathic group. There was no relation of neuropathy with the duration of RA, seropositivity, joint erosions, joint deformities, prior disease-modifying anti-rheumatic drugs or glucocorticoid intake, and 28-joint disease activity score. Neuropathy in RA was mostly subclinical and predominantly axonal. Pathologically, neuropathy secondary to amyloid infiltration was second only to vasculitic neuropathy. Absence of deep tendon jerks and presence of vasculitis were more commonly observed in patients with neuropathy.

Neurological Complications of Celiac Disease and Autoimmune Mechanisms: Preliminary Data of a Prospective Study in Adult Patients

Antibodies to gangliosides and Purkinje cells have been reported in patients with celiac disease (CD) with neuropathy and ataxia, respectively. Whether these antibodies are pathogenic is not clear. The response of neurological symptoms and antibody titers to a gluten-free diet is still controversial. The objective of our study was to assess whether neurological manifestations in CD patients correlate with antibody titers and a gluten-free diet.Thirty-five CD patients (9 males, 26 females, mean age 37.1 +/- 12.6 yrs) were followed prospectively. At initial evaluation, 23 were on a gluten-free diet, 12 were not. At recruitment and during follow-up, patients underwent neurological and electrophysiological evaluation. IgG, IgM, and IgA anti-ganglioside antibodies were assayed by ELISA; anti-neuronal antibodies were assessed by immunohistochemistry and Western blot. Four patients, all males, had electrophysiological evidence of neuropathy; three had been on a gluten-free diet for several months, and one was newly diagnosed. One had reduced tendon reflexes; another complained of distal paresthesias. With regard to anti-ganglioside antibodies, three patients had a moderate increase in antibodies without symptoms or signs of neuropathy. No patients had ataxia or cerebellar dysfunction, although in four patients reactivity to neuronal antigens was found. In 17 patients, an electrophysiological follow-up (mean duration of follow-up, 9 months) showed no changes. In conclusion, the preliminary results of this prospective study indicate that neuropathy, usually subclinical, may accompany CD. Antibody titers do not seem to correlate with neurological symptoms/signs or diet. Ongoing follow-up will help confirm these data and clarify the role, if any, of antibodies in neurological involvement in CD.

Immunopathogenetic Role Of The M‐Protein In Neuropathy Associated With IgA Monoclonal Gammopathy

Neuropathy has been reported in some patients with IgA monoclonal gammopathy of undetermined significance (MGUS) but the clinical and pathogenetic relevance of this association remains unclear. This is because the clinical and electrophysiological features of the neuropathy in reported patients were quite heterogeneous and only occasionally endoneurial deposits or anti‐neural reactivity of IgA M‐proteins were found. In order to clarify the possible role of IgA M‐proteins in the neuropathy we studied their reactivity with nerve antigens in 12 patients with neuropathy associated with IgA MGUS and in 15 patients with IgA MGUS without clinical or electrophysiological evidence of neuropathy. Patients' sera were tested for IgA reactivity with the glycolipids GM1, GM2, GD1a, GD1b, GQ1b and sulfatides by ELISA and with central (CNS) and peripheral nervous system (PNS) myelin and whole nerve homogenates by Western Blot. No IgA reactivity with any of the gangliosides tested or sulfatide was detected by ELISA in patients with neuropathy and IgA MGUS. By Western blot only one neuropathy patient had an intense IgA reactivity with several protein bands of the molecular weight (MW) of 80 to 200 kD, including high MW neurofilaments. A similar though less intense IgA reactivity with the same bands was detected in one patient without neuropathy. No other reactivity with neural proteins was detected in patients' sera more frequently or more intensely than in controls. The clinical features of the neuropathy in the four patients whose clinical reports were available showed an usually mild, predominantly motor (2) or sensory (1) or mixed (1) impairment, while electrophysiological studies showed a predominant axonal (2), demyelinating (1) or mixed (1) neuropathy. In the only patient in whom sural nerve biopsy was performed no endoneurial deposits of IgA were found. The heterogeneity of the clinical and electrophysiological findings in these patients together with the lack of a consistent pattern of IgA reactivity with neural antigens in the 12 patients examined fail to support, at least in these patients, a possible immunopathogenetic role of the IgA M‐proteins in the neuropathy.

Structural and functional changes in skeletal muscle in anorexia nervosa.

Protein-energy malnutrition in anorexia nervosa is an under-recognised cause of muscle dysfunction. To characterise the skeletal myopathy that occurs in patients with severe anorexia nervosa, muscle function and structure were comprehensively examined in eight young adult female patients with severe (40%) self-induced weight loss. All of the patients showed impaired muscle function on strength and exercise measurement. The maximum voluntary contraction force for the patient group was significantly less than predicted values. Electromyography revealed myopathy in five of the patients, four of whom also had electro-physiological evidence of neuropathy. However, muscle biopsy specimens consistently showed myopathic changes with severe type 2 fibre atrophy but with no evidence of neuropathic changes. Ultrastructurally, there was separation and segmental loss of myofibrils and most biopsy samples contained abundant glycogen granules; we have previously reported that one of the most consistent biochemical abnormalities in these patients is impaired ischaemic lactate responses to forearm exercise. The result of severe protein-energy malnutrition on the musculo-skeletal system is a metabolic myopathy. Although the patients admitted to a variety of abnormal dieting behaviours, such as over-exercising and self-induced vomiting, no association was found between any of these and quantitative histological changes in the muscle biopsy samples. It is recommended that myopathy in anorexia nervosa be treated by instituting an appropriate refeeding programme.

Magnetic Resonance Imaging in Non-Traumatic Canalicular Peripheral Neuropathy of the Arm

The term canalicular neuropathy is applied to nerve lesions arising on nerve segments passing through the osteofibrous canals or other narrow orifices and resulting in nerve compression and entrapment. We studied 31 patients referred to us for non-traumatic canalicular syndromes in the upper limbs. After clinical, electrophysiological and morphological analysis of each case, we emphasize the role of MR imaging in establishing prognosis and selecting treatment. Anatomosurgical specimens correlated well with MR features, whereas there was little correlation between electrophysiological severity and anatomical changes. In summary, canalicular neuropathy is a clinical syndrome. The aim of MR investigation is to document the morphological changes which will serve to institute appropriate treatment. When patients have clinical and electrophysiological evidence of neuropathy without MR demonstration of the nerve lesion, therapy will be conservative, thus saving the cost and risk of surgery. On the other hand, when clinical and electrophysiological findings are flanked by MR demonstration of the neuropathy, the disease is known to be advanced and surgery will be indicated to prevent neurotmesis.

Neuropathy in chronic obstructive pulmonary disease: a multicentre electrophysiological and clinical study

The incidence and type of neuropathy in patients with chronic obstructive pulmonary disease (COPD) were assessed. In a selected group of 89 patients, abnormal nerve conduction studies were found in 44%. Electrophysiological signs of a generalized peripheral neuropathy were found in 5-18%, depending on diagnostic criteria. Lesions which were thought to be due to compression or other forms of trauma were present in a further 24%. In the patients with peripheral neuropathy, the changes were distally predominant, affected mainly sensory fibres, and were consistent with an axonal type of neuropathy. There was a significant correlation between age and the incidence of peripheral neuropathy. Electrophysiological evidence of neuropathy was three times as common as clinical evidence. Much of the variation in the reported incidence of neuropathy in COPD is probably due to imprecise diagnostic criteria.

Silicone Gel Infiltration of a Peripheral Nerve and Constrictive Neuropathy following Rupture of a Breast Prosthesis

Following rupture of a subpectoral breast prosthesis, massive amounts of silicone gel migrated into the arm of a patient. The patient developed painful paresthesias and decreased sensation in the cutaneous distribution of the superficial radial nerve. Nerve conduction studies showed both an increase in distal latency and decreased amplitude in this nerve compared with the normal opposite side. Subsequent neurolysis confirmed dense fibrosis surrounding the nerve. Silicone droplets also were observed within the thickened epineurium of the median nerve, but no electrophysiologic evidence of neuropathy occurred. Multiple debridements of the subcutaneous tissue of the arm were necessary. In one of these specimens, histologic sections demonstrated silicone gel infiltration of a subcutaneous nerve. This is the first reported case of silicone gel infiltration of a nerve and constrictive neuropathy associated with a prosthesis rupture.

Sural nerve morphology in asymptomatic uremia.

This study evaluates morphologically the sural nerves of two patients with acute and another pair with chronic uremia, both of whom had neither clinical nor electrophysiologic evidence of neuropathy. Morphometric changes indicative of myelin repair were noted in the chronic uremic case who had a shorter duration of renal failure but required dialysis. Also, changes suggestive of axonal degeneration were found in the case who had chronic uremia of long duration. Both cases of acute uremia did not reveal significant abnormalities. Structural changes in the sural nerves may precede clinical and nerve conduction derangements in uremia, specifically in chronic cases.

Electrophysiological studies in diabetic neuropathy.

In 30 patients with diabetic neuropathy sensory potentials in the median nerve, motor conduction in the lateral popliteal and median nerves, and electromyographic findings in distal and proximal muscles were compared with the severity of symptoms and signs. All patients had abnormalities in at least one of the electrophysiological parameters. The sensory potentials were the most sensitive indicator of subclinical involvement; abnormalities were found in 24 patients, 12 of whom had no sensory symptoms or signs and five of whom had no other clinical or electrophysiological evidence of neuropathy in the upper extremities. This indicates that sensory nerve fibres may be affected before motor. The next most sensitive parameter was the presence of fibrillation potentials, found in more than half the distal muscles examined. Slowing in motor conduction in the lateral popliteal nerve was the only electrophysiological change correlated to the severity of the neuropathy, and no other electrophysiological parameter was correlated to the duration or the severity of the neuropathy or the diabetes. An onset of neuropathy before or simultaneously with the manifestations of the diabetes, as well as the frequent occurrence of asymptomatic changes in sensory conduction, support the evidence at hand that the neuropathy develops concomitantly with and as an integral part of the metabolic disturbance rather than as a consequence of the vascular complications of diabetes. Of three patients with clinical signs or symptoms of a diabetic amyotrophy, two had asymptomatic electrophysiological abnormalities in distal nerves and muscles, consistent with widespread involvement of the peripheral nerves. The third patient had electromyographic changes in the medial vastus muscles suggestive of a myopathy. Motor and sensory conduction in distal and proximal nerves were normal.